Glucose enhancement of a facial recognition task in young adults.

PubMed

Metzger, M M

2000-02-01

Numerous studies have reported that glucose administration enhances memory processes in both elderly and young adult subjects. Although these studies have utilized a variety of procedures and paradigms, investigations of both young and elderly subjects have typically used verbal tasks (word list recall, paragraph recall, etc.). In the present study, the effect of glucose consumption on a nonverbal, facial recognition task in young adults was examined. Lemonade sweetened with either glucose (50 g) or saccharin (23.7 mg) was consumed by college students (mean age of 21.1 years) 15 min prior to a facial recognition task. The task consisted of a familiarization phase in which subjects were presented with "target" faces, followed immediately by a recognition phase in which subjects had to identify the targets among a random array of familiar target and novel "distractor" faces. Statistical analysis indicated that there were no differences on hit rate (target identification) for subjects who consumed either saccharin or glucose prior to the test. However, further analyses revealed that subjects who consumed glucose committed significantly fewer false alarms and had (marginally) higher d-prime scores (a signal detection measure) compared to subjects who consumed saccharin prior to the test. These results parallel a previous report demonstrating glucose enhancement of a facial recognition task in probable Alzheimer's patients; however, this is believed to be the first demonstration of glucose enhancement for a facial recognition task in healthy, young adults.

Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

PubMed

Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

2016-08-09

Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

PubMed

Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

2017-01-01

A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m 2 ) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

PubMed

Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

2016-12-01

The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis.

PubMed

Byberg, S; Hansen, A-L S; Christensen, D L; Vistisen, D; Aadahl, M; Linneberg, A; Witte, D R

2012-09-01

Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c), two measures of insulin sensitivity (the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Altered glucose kinetics in diabetic rats during Gram-negative infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lang, C.H.; Dobrescu, C.; Bagby, G.J.

The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabeticmore » group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge.« less

Glucose release in mantle tissue of Mytilus: regulation by calcium ions.

PubMed

Crespo, C A; Espinosa, J

1990-09-01

Glucose release activity in mantle tissue of Mytilus galloprovincialis was studied. Mantle tissue shows a basal glucose releasing activity. The external Ca2+ absence increases 2 to 3-fold the basal glucose release, and when A23187 (10 microM) was simultaneously present the release doubled that obtained in Ca2(+)-absence. EGTA (2 mM), chlorpromazine (200 microM) and lanthanum (3 mM) decreased the glucose release promoted by external Ca2+ absence. This and other data suggest that glucose release activity in mantle tissue might be controlled by Ca2+ ions.

P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells.

PubMed

Varshney, Pallavi; Dey, Chinmoy Sankar

2016-07-05

P21-activated kinases (PAKs) are recently reported as important players of insulin signaling and glucose homeostasis in tissues like muscle, pancreas and liver. However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance. Irrespective of insulin sensitivity, insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2 over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of PP2A resulted in increased PAK2 activity, with corresponding changes in glucose uptake. Taken together, present study demonstrates an inhibitory role of insulin signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1-dependent negative regulator of neuronal glucose uptake and insulin sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dynamic modeling of the hydrogel molecular filter in a metamaterial biosensing system for glucose concentration estimation.

PubMed

Teutsch, T; Mesch, M; Giessen, H; Tarin, C

2014-01-01

We present a novel concept for ophthalmic glucose sensing using a biosensing system that consists of plasmonic dipole metamaterial covered by a layer of functionalized hydrogel. The metamaterial together with the hydrogel can be integrated into a contact lens. This optical sensor changes its properties such as reflectivity upon the ambient glucose concentration, which allows in situ measurements in the eye. The functionalization of the sensor with hydrogel allows for a glucose-specific detection, providing both selectivity and sensitivity. As a result of the presented work we derive a dynamic model of the hydrogel that can be used for further simulation studies.

Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition

PubMed Central

HAN, NING; YU, LI; SONG, ZHIDU; LUO, LIFU; WU, YAZHEN

2015-01-01

Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy. PMID:25816073

Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition.

PubMed

Han, Ning; Yu, Li; Song, Zhidu; Luo, Lifu; Wu, Yazhen

2015-07-01

Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy.

Frequency of impaired glucose tolerance and diabetes mellitus in subjects with fasting blood glucose below 6.1 mmol/L (110 mg/dL).

PubMed

Khan, S H; Ijaz, A; Bokhari, S A Raza; Hanif, M S; Azam, N

2013-02-01

The diagnosis of diabetes mellitus by the available criteria is controversial and relies heavily on fasting glucose results. This cross-sectional study in 2010-2011 aimed to measure the frequency of impaired glucose tolerance and diabetes mellitus in 127 subjects having fasting blood glucose < 7.0 mmol/L and to measure the agreement between different standard diagnostic criteria. Subjects presenting to a laboratory for analysis of fasting blood glucose for excluding diabetes mellitus underwent a 2-hour 75 g oral glucose challenge. A total of 40.6% of subjects with fasting blood glucose from 5.6-6.0 mmol/L had abnormal glucose regulation on the basis ofthe gold standard glucose challenge. Agreement between American Diabetes Association and World Health Organization diagnostic criteria was only fair (kappa = 0.32). Abnormalities of glucose metabolism including impaired glucose tolerance and diabetes mellitus can exist at fasting blood glucose results < 6.1 mmol/L (110 mg/dL).

Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

PubMed

Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

2015-01-01

In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

Effect of Cinnamon Tea on Postprandial Glucose Concentration.

PubMed

Bernardo, Maria Alexandra; Silva, Maria Leonor; Santos, Elisabeth; Moncada, Margarida Maria; Brito, José; Proença, Luis; Singh, Jaipaul; de Mesquita, Maria Fernanda

2015-01-01

Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p < 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained from C. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period.

An Improved Method for Studying the Enzyme-Catalyzed Oxidation of Glucose Using Luminescent Probes

ERIC Educational Resources Information Center

Bare, William D.; Pham, Chi V.; Cuber, Matthew; Demas, J. N.

2007-01-01

A new method is presented for measuring the rate of the oxidation of glucose in the presence of glucose oxidase. The improved method employs luminescence measurements to directly determine the concentration of oxygen in real time, thus obviating complicated reaction schemes employed in previous methods. Our method has been used to determine…

Effects of two doses of glucose and a caffeine-glucose combination on cognitive performance and mood during multi-tasking.

PubMed

Scholey, Andrew; Savage, Karen; O'Neill, Barry V; Owen, Lauren; Stough, Con; Priestley, Caroline; Wetherell, Mark

2014-09-01

This study assessed the effects of two doses of glucose and a caffeine-glucose combination on mood and performance of an ecologically valid, computerised multi-tasking platform. Following a double-blind, placebo-controlled, randomised, parallel-groups design, 150 healthy adults (mean age 34.78 years) consumed drinks containing placebo, 25 g glucose, 60 g glucose or 60 g glucose with 40 mg caffeine. They completed a multi-tasking framework at baseline and then 30 min following drink consumption with mood assessments immediately before and after the multi-tasking framework. Blood glucose and salivary caffeine were co-monitored. The caffeine-glucose group had significantly better total multi-tasking scores than the placebo or 60 g glucose groups and were significantly faster at mental arithmetic tasks than either glucose drink group. There were no significant treatment effects on mood. Caffeine and glucose levels confirmed compliance with overnight abstinence/fasting, respectively, and followed the predicted post-drink patterns. These data suggest that co-administration of glucose and caffeine allows greater allocation of attentional resources than placebo or glucose alone. At present, we cannot rule out the possibility that the effects are due to caffeine alone Future studies should aim at disentangling caffeine and glucose effects. © 2014 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd.

Effects of two doses of glucose and a caffeine–glucose combination on cognitive performance and mood during multi-tasking

PubMed Central

Scholey, Andrew; Savage, Karen; O'Neill, Barry V; Owen, Lauren; Stough, Con; Priestley, Caroline; Wetherell, Mark

2014-01-01

Background This study assessed the effects of two doses of glucose and a caffeine–glucose combination on mood and performance of an ecologically valid, computerised multi-tasking platform. Materials and methods Following a double-blind, placebo-controlled, randomised, parallel-groups design, 150 healthy adults (mean age 34.78 years) consumed drinks containing placebo, 25 g glucose, 60 g glucose or 60 g glucose with 40 mg caffeine. They completed a multi-tasking framework at baseline and then 30 min following drink consumption with mood assessments immediately before and after the multi-tasking framework. Blood glucose and salivary caffeine were co-monitored. Results The caffeine–glucose group had significantly better total multi-tasking scores than the placebo or 60 g glucose groups and were significantly faster at mental arithmetic tasks than either glucose drink group. There were no significant treatment effects on mood. Caffeine and glucose levels confirmed compliance with overnight abstinence/fasting, respectively, and followed the predicted post-drink patterns. Conclusion These data suggest that co-administration of glucose and caffeine allows greater allocation of attentional resources than placebo or glucose alone. At present, we cannot rule out the possibility that the effects are due to caffeine alone Future studies should aim at disentangling caffeine and glucose effects. PMID:25196040

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vikram, A.; Tripathi, D.N.; Ramarao, P.

Streptozotocin (STZ) is a naturally occurring compound isolated from Streptomyces achromogens. It is used extensively for inducing diabetes in experimental animals. Diabetes mellitus is known to have proven adverse effects on male sexual organs and their reproductive functions. The atrophy of prostate gland and other organs of the genitourinary tract were observed in experimental diabetic animals. STZ exhibits a structural resemblance to D-glucose due to the presence of sugar moiety in its structure. Pancreatic {beta}-cells mainly contain GLUT1 and GLUT2 glucose transporters. Possibly due to structural resemblance, STZ and D-glucose, share a common recognition site for entry into the {beta}-cells.more » The objective of the present study is to evaluate the effect of D-glucose on STZ-induced toxicity in accessory sex organs of male rats. Animals were kept on overnight fasting. One group received vehicle and served as negative control, while all other groups were given STZ (45 mg/kg). Animals that received only STZ served as positive control. The effect of D-glucose was studied on STZ treated animals with different dosage of D-glucose (250, 500, 1000 and 2000 mg/kg). Restoration of body weight, plasma glucose and plasma insulin was evident only at 1000 and 2000 mg/kg of D-glucose. The protective effect of D-glucose is evident only when it is administered simultaneously with STZ. In the present investigation, we report that simultaneous administration of D-glucose along with STZ ameliorates STZ-induced toxicity. This is evident from the restoration of accessory sex organ's weight, cellular morphology as well as insulin level.« less

Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

PubMed Central

Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

2016-01-01

Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

Biotin enhances ATP synthesis in pancreatic islets of the rat, resulting in reinforcement of glucose-induced insulin secretion.

PubMed

Sone, Hideyuki; Sasaki, Yuka; Komai, Michio; Toyomizu, Masaaki; Kagawa, Yasuo; Furukawa, Yuji

2004-02-13

Previous studies showed that biotin enhanced glucose-induced insulin secretion. Changes in the cytosolic ATP/ADP ratio in the pancreatic islets participate in the regulation of insulin secretion by glucose. In the present study we investigated whether biotin regulates the cytosolic ATP/ADP ratio in glucose-stimulated islets. When islets were stimulated with glucose plus biotin, the ATP/ADP ratio increased to approximately 160% of the ATP/ADP ratio in islets stimulated with glucose alone. The rate of glucose oxidation, assessed by CO(2) production, was also about 2-fold higher in islets treated with biotin. These increasing effects of biotin were proportional to the effects seen in insulin secretion. There are no previous reports of vitamins, such as biotin, directly affecting ATP synthesis. Our data indicate that biotin enhances ATP synthesis in islets following the increased rate of substrate oxidation in mitochondria and that, as a consequence of these events, glucose-induced insulin release is reinforced by biotin.

Blood glucose screening among elderly Malaysians: Who to target?

PubMed

Cheah, Yong Kang; Goh, Kim-Leng

2017-01-01

Early detection of raised blood glucose can reduce the risk of developing diabetes. Despite being a high-risk group, a significant proportion of the elderly population does not undergo blood glucose screening. The aim of the present study was to examine the factors affecting blood glucose screening among the elderly. Data from a sample of 2463 respondents in the National Health and Morbidity Survey 2011 were used. Pearson Chi-squared tests were conducted to find factors associated with screening behavior. A logit model was used to analyze the likelihood of screening. Income, age, education, ethnicity, employment status, availability of medical coverage, and smoking behavior were significantly associated with blood glucose screening. The likelihood of blood glucose screening was positively correlated with available monthly income and was higher in those aged 60-69 years, those attaining higher education, Malays, and elderly who are medically covered. The findings of the present study provide insights for health policy formulation for the elderly. As part of their efforts to reduce national health costs, governments should pay particular attention to the elderly, who are likely to be unscreened for blood glucose levels, because they face even larger risk exposure. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Effects of glucose load on cognitive functions in elderly people.

PubMed

van der Zwaluw, Nikita L; van de Rest, Ondine; Kessels, Roy P C; de Groot, Lisette C P G M

2015-02-01

Glucose is the main fuel for the brain, and manipulation of the glucose supply may consequently affect brain function. The present review was conducted to provide an overview of studies that investigated the acute effects of glucose load on memory and other cognitive functions in elderly people. The effects of sucrose on cognition and suggested mechanisms were also explored. A total of twenty studies met the inclusion criteria. In the majority of studies, episodic memory was investigated and a beneficial role for glucose in that specific cognitive domain was suggested. Other cognitive domains, i.e., working memory, semantic memory, visual memory, information-processing speed, attention, executive function, and visual/spatial function, have been studied less frequently and evidence for a beneficial effect of glucose was equivocal. Mechanisms are suggested to be mainly related to the human body's need for glucose as a metabolic substrate for physiological mechanisms in both central and peripheral processes. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Beneficial Effects of Pentanema vestitum Linn. Whole Plant on the Glucose and Other Biochemical Parameters of Alloxan Induced Diabetic Rabbits

PubMed Central

Ilahi, Ikram; Asghar, Ali; Ali, Shujat; Khan, Murad; Khan, Nasrullah

2012-01-01

The residents of Lower Dir and Malakand agency, Khyber Pakhtunkhwa, Pakistan, use the dry powder of whole plant of Pentanema vestitum for the treatment of asthma and diabetes. No documented reports are available about the therapeutic action of Pentanema vestitum. The present study was aimed to explore the antihyperglycemic effect of 70% methanol extract of Pentanema vestitum whole plant in glucose-induced nondiabetic hyperglycemic and alloxan-induced diabetic rabbits. During this study, the effects of plant extract on the serum lipid profile, GPT, ALP, bilirubin and creatinine of diabetic rabbits were also studied. The extract of Pentanema vestitum whole plant exhibited significant (P < 0.05) antihyperglycemic activity in glucose-induced hyperglycemic rabbits. Treatment of alloxan-induced diabetic rabbits with extract significantly (P < 0.05) reduced the elevated levels of serum glucose, GPT, ALP, bilirubin and creatinine. During the study of lipid profile, the extract proved to be antihyperlipidemic and HDL boosting in diabetic rabbit models. From the finding of the present research, it was concluded that the 70% methanol extract of Pentanema vestitum whole plant has beneficial effects on serum levels of glucose, lipid profile, GPT, ALP, bilirubin, and creatinine of diabetic rabbits. PMID:23316385

Postprandial glucose and insulin levels in type 2 diabetes mellitus patients after consumption of ready-to-eat mixed meals.

PubMed

Manios, Yannis; Moschonis, George; Mavrogianni, Christina; Tsoutsoulopoulou, Konstantina; Kogkas, Stergios; Lambrinou, Christina-Paulina; Efstathopoulou, Eirini

2017-04-01

To compare the effects of three ready-to-eat mixed meals, with a high fiber content and low glycemic index, on postprandial glycemic and insulinemic response in patients with Type 2 diabetes mellitus (T2DM). The current study followed a prospective, three-way, cross-over design. Twenty-four patients with T2DM consumed three ready-to-eat mixed meals, i.e., "wild greens pie" (meal 1), "chicken burgers with boiled vegetables" (meal 2) and "vegetable moussaka" (meal 3) and an oral glucose load, all providing 50 g of carbohydrates. Venous blood was collected at 0, 30, 60, 90 and 120 min postprandial. Statistical analyses included repeated measures analysis of variance and calculations of the area under the glucose and insulin curves (AUC) for each one of the test meals and the oral glucose load. Patients consuming each one of the three mixed meals showed better postprandial glycemic responses compared to the oral glucose load (P < 0.001). Furthermore, patients consuming meal 3 showed a better insulinemic response compared to the oral glucose load and meal 1, after 60 and 120 min postprandial, respectively (P < 0.05). In addition, the increase observed in HOMA-IR values from T0 to T120 was significantly lower for meal 3, compared to the oral glucose load (P < 0.001). The three ready-to-eat mixed meals examined in the present study were found to elicit significantly lower glycemic responses compared to the oral glucose load in diabetic patients. The mixed meals examined in the present study could be proposed as effective, palatable and practical solutions for diabetics for glucose control.

Novel role of insulin in the regulation of glucose excretion by mourning doves (Zenaida macroura).

PubMed

Sweazea, Karen L; Braun, Eldon J; Sparr, Richard

2017-06-01

In mammals, insulin primarily lowers plasma glucose (P Glu ) by increasing its uptake into tissues. Studies have also shown that insulin lowers P Glu in mammals by modulating glomerular filtration rate (GFR). Birds have naturally high P Glu and, although insulin administration significantly decreases glucose concentrations, birds are resistant to insulin-mediated glucose uptake into tissues. Since prior work has not examined the effects of insulin on GFR in birds, the purpose of the present study was to assess whether insulin can augment renal glucose excretion and thereby lower P Glu . Therefore, the hypothesis of the present study was that insulin lowers P Glu in birds by augmenting GFR, as estimated by inulin clearance (C In ). Adult mourning doves (Zenaida macroura) were used as experimental animals. Doves were anesthetized and the brachial vein was cannulated for administration of [ 14 C]-inulin and insulin and the brachial artery was cannulated for blood collections. Ureteral urine was collected via a catheter inserted into the cloaca. Ten minutes following administration of exogenous insulin (400μg/kg body mass, i.v.) plasma glucose was significantly decreased (p=0.0003). Twenty minutes following insulin administration, increases in GFR (p=0.016) were observed along with decreases in urine glucose concentrations (p=0.008), glucose excretion (p=0.028), and the fractional excretion of glucose (p=0.003). Urine flow rate (p=0.051) also tended to increase after administration of insulin. These data demonstrate a significant role for insulin in modulating GFR in mourning doves, which may in part explain the lower P Glu measured following insulin administration. Copyright © 2017 Elsevier GmbH. All rights reserved.

Follow-up of blood glucose distribution characteristics in a health examination population in Chengdu from 2010 to 2016.

PubMed

Wang, Yuting; Xu, Wangdong; Zhang, Qiongying; Bao, Ting; Yang, Hanwei; Huang, Wenxia; Tang, Huairong

2018-02-01

The worldwide prevalence and incidence of diabetes and obesity are increasing in pandemic proportions. Thus, regular health examination is an important way for early detection of diabetes and glucose intolerance. The present study aims to detect the blood glucose distribution characteristics of the participants in the Health Examination Center at West China Hospital, Sichuan University from 2010 to 2016.A prospective cohort included 9168 Chinese participants, aged 18 years or more, who had available information on fasting blood glucose concentrations at the start of the study (2010). Examination surveys were conducted every year from 2010 to 2016. Cases having serum level of fasting blood glucose between 2.2 and 6.1 mmol/L were considered as normality, while serum level of fasting blood glucose < 2.2 or higher than 6.2 mmol/L were considered as abnormality.The percentage of participants having normal level of glucose was gradually reduced both in males and females from 2010 to 2016, by which the percentage of males having normal level of glucose was significantly lower than that in females. Moreover, the mean level of glucose was significantly increased from 2010 to 2016 both in males and females overall, and the mean level of glucose was higher in males compared with that in females every year. Furthermore, we showed that the level of glucose was gradually increased year by year in each age group, and the level of glucose was higher in aged cases compared with the young population.The study population in the current study showed higher levels of glucose with ages increasing, and males indicated higher expression of glucose than that in females. Some preventive action may be adopted early and more attention can be paid to this health-examination population.

Butyric acid production from lignocellulosic biomass hydrolysates by engineered Clostridium tyrobutyricum overexpressing xylose catabolism genes for glucose and xylose co-utilization.

PubMed

Fu, Hongxin; Yang, Shang-Tian; Wang, Minqi; Wang, Jufang; Tang, I-Ching

2017-06-01

Clostridium tyrobutyricum can utilize glucose and xylose as carbon source for butyric acid production. However, xylose catabolism is inhibited by glucose, hampering butyric acid production from lignocellulosic biomass hydrolysates containing both glucose and xylose. In this study, an engineered strain of C. tyrobutyricum Ct-pTBA overexpressing heterologous xylose catabolism genes (xylT, xylA, and xylB) was investigated for co-utilizing glucose and xylose present in hydrolysates of plant biomass, including soybean hull, corn fiber, wheat straw, rice straw, and sugarcane bagasse. Compared to the wild-type strain, Ct-pTBA showed higher xylose utilization without significant glucose catabolite repression, achieving near 100% utilization of glucose and xylose present in lignocellulosic biomass hydrolysates in bioreactor at pH 6. About 42.6g/L butyrate at a productivity of 0.56g/L·h and yield of 0.36g/g was obtained in batch fermentation, demonstrating the potential of C. tyrobutyricum Ct-pTBA for butyric acid production from lignocellulosic biomass hydrolysates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glucose modulates food-related salience coding of midbrain neurons in humans.

PubMed

Ulrich, Martin; Endres, Felix; Kölle, Markus; Adolph, Oliver; Widenhorn-Müller, Katharina; Grön, Georg

2016-12-01

Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low-caloric food (LC), high-caloric food (HC), and non-food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment-specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376-4384, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Analytical model for real time, noninvasive estimation of blood glucose level.

PubMed

Adhyapak, Anoop; Sidley, Matthew; Venkataraman, Jayanti

2014-01-01

The paper presents an analytical model to estimate blood glucose level from measurements made non-invasively and in real time by an antenna strapped to a patient's wrist. Some promising success has been shown by the RIT ETA Lab research group that an antenna's resonant frequency can track, in real time, changes in glucose concentration. Based on an in-vitro study of blood samples of diabetic patients, the paper presents a modified Cole-Cole model that incorporates a factor to represent the change in glucose level. A calibration technique using the input impedance technique is discussed and the results show a good estimation as compared to the glucose meter readings. An alternate calibration methodology has been developed that is based on the shift in the antenna resonant frequency using an equivalent circuit model containing a shunt capacitor to represent the shift in resonant frequency with changing glucose levels. Work under progress is the optimization of the technique with a larger sample of patients.

Analytical and Clinical Performance of Blood Glucose Monitors

PubMed Central

Boren, Suzanne Austin; Clarke, William L.

2010-01-01

Background The objective of this study was to understand the level of performance of blood glucose monitors as assessed in the published literature. Methods Medline from January 2000 to October 2009 and reference lists of included articles were searched to identify eligible studies. Key information was abstracted from eligible studies: blood glucose meters tested, blood sample, meter operators, setting, sample of people (number, diabetes type, age, sex, and race), duration of diabetes, years using a glucose meter, insulin use, recommendations followed, performance evaluation measures, and specific factors affecting the accuracy evaluation of blood glucose monitors. Results Thirty-one articles were included in this review. Articles were categorized as review articles of blood glucose accuracy (6 articles), original studies that reported the performance of blood glucose meters in laboratory settings (14 articles) or clinical settings (9 articles), and simulation studies (2 articles). A variety of performance evaluation measures were used in the studies. The authors did not identify any studies that demonstrated a difference in clinical outcomes. Examples of analytical tools used in the description of accuracy (e.g., correlation coefficient, linear regression equations, and International Organization for Standardization standards) and how these traditional measures can complicate the achievement of target blood glucose levels for the patient were presented. The benefits of using error grid analysis to quantify the clinical accuracy of patient-determined blood glucose values were discussed. Conclusions When examining blood glucose monitor performance in the real world, it is important to consider if an improvement in analytical accuracy would lead to improved clinical outcomes for patients. There are several examples of how analytical tools used in the description of self-monitoring of blood glucose accuracy could be irrelevant to treatment decisions. PMID:20167171

Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

PubMed

Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O

2004-12-01

Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats. 2004 John Wiley & Sons, Ltd.

Fasting glucose and glucose tolerance as potential predictors of neurocognitive function among nondiabetic older adults.

PubMed

Sims Wright, Regina; Levy, Shellie-Anne T; Katzel, Leslie I; Rosenberger, William F; Manukyan, Zorayr; Whitfield, Keith E; Waldstein, Shari R

2015-01-01

Significant evidence has demonstrated that Type 2 diabetes mellitus and related precursors are associated with diminished neurocognitive function and risk of dementia among older adults. However, very little research has examined relations of glucose regulation to neurocognitive function among older adults free of these conditions. The primary aim of this investigation was to examine associations among fasting glucose, glucose tolerance, and neurocognitive function among nondiabetic older adults. The secondary aim was to examine age, gender, and education as potential effect modifiers. The study employed a cross-sectional, correlational study design. Participants were 172 older adults with a mean age of 64.43 years (SD = 13.09). The sample was 58% male and 87% White. Participants completed an oral glucose tolerance test as part of a larger study. Trained psychometricians administered neuropsychological tests that assessed performance in the domains of response inhibition, nonverbal memory, verbal memory, attention and working memory, visuoconstructional abilities, visuospatial abilities, psychomotor speed and executive function, and motor speed and manual dexterity. Linear multiple regressions were run to test study aims. No significant main effects of fasting glucose and 2-hour glucose emerged for performance on any neurocognitive test; however, significant interactions were present. Higher fasting glucose was associated with poorer short-term verbal memory performance among men, but unexpectedly better response inhibition and long-term verbal memory performance for participants over age 70. Higher 2-hour glucose values were associated with reduced divided attention performance among participants with less than a high school education. Mixed findings suggest that glucose levels may be both beneficial and deleterious to neurocognition among nondiabetic older adults. Additional studies with healthy older adults are needed to confirm this unexpected pattern of associations; however, findings have implications for the importance of maintaining healthy glucose levels in older adulthood.

Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons.

PubMed

Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2006-10-01

Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-beta-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

β-Hydroxybutyrate is the preferred substrate for GABA and glutamate synthesis while glucose is indispensable during depolarization in cultured GABAergic neurons.

PubMed

Lund, Trine M; Obel, Linea F; Risa, Øystein; Sonnewald, Ursula

2011-08-01

The ketogenic diet has multiple beneficial effects not only in treatment of epilepsy, but also in that of glucose transporter 1 deficiency, cancer, Parkinson's disease, obesity and pain. Thus, there is an increasing interest in understanding the mechanism behind this metabolic therapy. Patients on a ketogenic diet reach high plasma levels of ketone bodies, which are used by the brain as energy substrates. The interaction between glucose and ketone bodies is complex and there is still controversy as to what extent it affects the homeostasis of the neurotransmitters glutamate, aspartate and GABA. The present study was conducted to study this metabolic interaction in cultured GABAergic neurons exposed to different combinations of (13)C-labeled and unlabeled glucose and β-hydroxybutyrate. Depolarization was induced and the incorporation of (13)C into glutamate, GABA and aspartate was analyzed. The presence of β-hydroxybutyrate together with glucose did not affect the total GABA content but did, however, decrease the aspartate content to a lower value than when either glucose or β-hydroxybutyrate was employed alone. When combinations of the two substrates were used (13)C-atoms from β-hydroxybutyrate were found in all three amino acids to a greater extent than (13)C-atoms from glucose, but only the (13)C contribution from [1,6-(13)C]glucose increased upon depolarization. In conclusion, β-hydroxybutyrate was preferred over glucose as substrate for amino acid synthesis but the total content of aspartate decreased when both substrates were present. Furthermore only the use of glucose increased upon depolarization. Copyright © 2011 Elsevier B.V. All rights reserved.

High glucose impaired estrogen receptor alpha signaling via β-catenin in osteoblastic MC3T3-E1.

PubMed

Wang, Rui; Gao, Dong; Zhou, Yin; Chen, Lu; Luo, Bin; Yu, Yanrong; Li, Hao; Hu, Jiawei; Huang, Qiren; He, Ming; Peng, Weijie; Luo, Dan

2017-11-01

Diabetic Mellitus is a risk factor for osteoporosis. It has been suggested that altered estrogen or estrogen receptor α/β (ERα/β) signaling may be involved in diabetic osteoporosis. The present study is to investigate the effects of high glucose on ERα/β signaling in osteoblastic MC3T3-E1 and how the altered signaling of ERα/β affect osteoblastic bone formation. ERα/β signaling was demonstrated as ERα/β protein expression (Western Blotting) and ER transcription activity (Luciferase Reporter assays). Proliferation (WSK-1 assaying), differentiation (ALP staining) and mineralization (Alizalard Red staining) of MC3T3-E1 were examined to evaluate bone formation function. It has been found that high glucose increased ERα/β expression dose-dependently and time-dependently, but high glucose (33mM) decreased ERα transcription activity. 17β-estradiol increased the ERα/β expression dose-dependently in normal medium, but decreased the ERα/β expression dose-dependently in medium with high glucose (33mM). High glucose decreased bone formation and also decreased the osteogenic effects of 17β-estradiol (10 -8 M). High glucose decreased β-catenin expression dose-dependently and time-dependently. LiCl, an inhibitor of β-catenin degradation, decreased ERα expression but increased ERα transcription activity. When compared with high glucose treatment, LiCl (5mM) increased ALP activity and calcified nodes. Besides, high glucose also decreased the protein expression PI-3K, pAKT/AKT, GSK-3β. In conclusion, the present study suggested that high glucose may impair ERα transcription activity by inhibiting β-catenin signaling in osteoblastic MC3T3-E1, leading decreased bone formation ligand-dependently or ligand-independently. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adding glucose to food and solutions to enhance fructose absorption is not effective in preventing fructose-induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption.

PubMed

Tuck, C J; Ross, L A; Gibson, P R; Barrett, J S; Muir, J G

2017-02-01

In healthy individuals, the absorption of fructose in excess of glucose in solution is enhanced by the addition of glucose. The present study aimed to assess the effects of glucose addition to fructose or fructans on absorption patterns and genesis of gastrointestinal symptoms in patients with functional bowel disorders. Randomised, blinded, cross-over studies were performed in healthy subjects and functional bowel disorder patients with fructose malabsorption. The area-under-the-curve (AUC) was determined for breath hydrogen and symptom responses to: (i) six sugar solutions (fructose in solution) (glucose; sucrose; fructose; fructose + glucose; fructan; fructan + glucose) and (ii) whole foods (fructose in foods) containing fructose in excess of glucose given with and without additional glucose. Intake of fermentable short chain carbohydrates (FODMAPs; fermentable, oligo-, di-, monosaccharides and polyols) was controlled. For the fructose in solution study, in 26 patients with functional bowel disorders, breath hydrogen was reduced after glucose was added to fructose compared to fructose alone [mean (SD) AUC 92 (107) versus 859 (980) ppm 4 h -1 , respectively; P = 0.034). Glucose had no effect on breath hydrogen response to fructans (P = 1.000). The six healthy controls showed breath hydrogen patterns similar to those with functional bowel disorders. No differences in symptoms were experienced with the addition of glucose, except more nausea when glucose was added to fructose (P = 0.049). In the fructose in foods study, glucose addition to whole foods containing fructose in excess of glucose in nine patients with functional bowel disorders and nine healthy controls had no significant effect on breath hydrogen production or symptom response. The absence of a favourable response on symptoms does not support the concomitant intake of glucose with foods high in either fructose or fructans in patients with functional bowel disorders. © 2016 The British Dietetic Association Ltd.

Determination of Glucose Concentration in Yeast Culture Medium

NASA Astrophysics Data System (ADS)

Hara, Seiichi; Kishimoto, Tomokazu; Muraji, Masafumi; Tsujimoto, Hiroaki; Azuma, Masayuki; Ooshima, Hiroshi

The present paper describes a sensor for measuring the glucose concentration of yeast culture medium. The sensor determines glucose concentration by measuring the yield of hydrogen peroxide produced by glucose oxidase, which is monitored as luminescence using photomultiplier. The present sensor is able to measure low glucose concentration in media in which yeast cells keep respiration state. We herein describe the system and the characteristics of the glucose sensor.

Carbon Source Requirements for Exopolysaccharide Production by Lactobacillus casei CG11 and Partial Structure Analysis of the Polymer

PubMed Central

Cerning, J.; Renard, C. M. G. C.; Thibault, J. F.; Bouillanne, C.; Landon, M.; Desmazeaud, M.; Topisirovic, L.

1994-01-01

Exopolysaccharide production by Lactobacillus casei CG11 was studied in basal minimum medium containing various carbon sources (galactose, glucose, lactose, sucrose, maltose, melibiose) at concentrations of 2, 5, 10, and 20 g/liter. L. casei CG11 produced exopolysaccharides in basal minimum medium containing each of the sugars tested; lactose and galactose were the poorest carbon sources, and glucose was by far the most efficient carbon source. Sugar concentrations had a marked effect on polymer yield. Plasmid-cured Muc- derivatives grew better in the presence of glucose and attained slightly higher populations than the wild-type strain. The values obtained with lactose were considerably lower for both growth and exopolysaccharide yield. The level of specific polymer production per cell obtained with glucose was distinctively lower for Muc- derivatives than for the Muc+ strain. The polymer produced by L. casei CG11 in the presence of glucose was different from that formed in the presence of lactose. The polysaccharide produced by L. casei CG11 in basal minimum medium containing 20 g of glucose per liter had an intrinsic viscosity of 1.13 dl/g. It was rich in glucose (76%), which was present mostly as 2- or 3-linked residues along with some 2,3 doubly substituted glucose units, and in rhamnose (21%), which was present as 2-linked or terminal rhamnose; traces of mannose and galactose were also present. PMID:16349427

Prevalence of Diabetes Mellitus and Prediabetes in Dalseong-gun, Daegu City, Korea.

PubMed

Lee, Jung-Eun; Jung, Sung-Chang; Jung, Gui-Hwa; Ha, Sung-Woo; Kim, Bo-Wan; Chae, Shung-Chull; Park, Wee-Hyun; Lim, Ji-Sun; Yang, Jin-Hoon; Kam, Sin; Chun, Byung-Yeol; Kim, Jong-Yeon; Lee, Jung-Jeung; Lee, Kyeong-Soo; Ahn, Moon-Young; Kim, Young-Ae; Kim, Jung-Guk

2011-06-01

The aim of the present study was to determine the population-based prevalence of diabetes mellitus (DM) and prediabetes in a rural district of Daegu City, Korea. Between August and November 2003, a community-based health survey of adults aged 20 years and older was performed in the rural district of Dalseong-gun in Daegu City. A total of 1,806 of all eligible individuals agreed to participate. Fasting plasma glucose was measured in all participants. Two hour oral glucose tolerance was measured in the 1,773 participants for whom there was neither an established diagnosis of DM nor evidence of DM according to fasting glucose levels. The prevalence of DM and prediabetes was determined according to the 2003 criteria of the American Diabetes Association. Subjects with prediabetes were classified into one of three categories of glucose intolerance: isolated impaired fasting glucose (IFG); isolated impaired glucose tolerance (IGT); or combined IFG and IGT. The prevalence of DM was 12.2%. The highest prevalence rates were observed in subjects in their seventies. A total of 34.7% of all subjects who were assigned a diagnosis of DM in the present study had not been diagnosed previously. The prevalence of prediabetes was 22.7%. The highest prevalence rates were observed in subjects in their fifties. The present study identified prevalence rates of 12.2% for DM (age-standardized prevalence rate [ASR], 6.8%), and 22.7% for prediabetes (ASR 18.5%). These results emphasize the need for community health promotion strategies to prevent or delay the onset of DM in individuals with prediabetes.

A Disposable Tear Glucose Biosensor—Part 1: Design and Concept Testing

PubMed Central

Bishop, Daniel K.; La Belle, Jeffrey T.; Vossler, Stephen R.; Patel, Dharmendra R.; Cook, Curtiss B.

2010-01-01

Background Tear glucose has been suggested previously as a potential approach for the noninvasive estimation of blood glucose. While the topic remains unresolved, an overview of previous studies suggests the importance of a tear sampling approach and warrants new technology development. A concept device is presented that meets the needs of a tear glucose biosensor. Methods Three approaches to chronoamperometric glucose sensing were evaluated, including glucose oxidase mediated by potassium ferricyanide or oxygen with a hydrogen peroxide catalyst, Prussian blue, and potassium ferricyanide-mediated glucose dehydrogenase. For tear sampling, calcium alginate, poly(2-hydroxyethyl methacrylate), and polyurethane foam were screened as an absorbent tear sampling material. A quantitative model based on the proposed function of concept device was created. Results For glucose sensing, it was found that potassium ferricyanide with glucose dehydrogenase was ideal, featuring oxygen insensitivity, long-term stability, and a lower limit of detection of 2 μM glucose. Polyurethane foam possessed all of the required characteristics for tear sampling, including reproducible sampling from a hydrogel-simulated, eye surface (4.2 ± 0.5 μl; n = 8). It is estimated that 100 μM of glucose tear fluid would yield 135 nA (14.9% relative standard deviation). Conclusion A novel concept device for tear glucose sampling was presented, and the key functions of this device were tested and used to model the performance of the final device. Based on these promising initial results, the device is achievable and within reach of current technical capabilities, setting the stage for prototype development. PMID:20307389

Fluctuations in Nucleus Accumbens Extracellular Glutamate and Glucose during Motivated Glucose-drinking Behavior: Dissecting the Neurochemistry of Reward

PubMed Central

Wakabayashi, Ken T.; Myal, Stephanie E.; Kiyatkin, Eugene A.

2015-01-01

While motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain’s excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward-related neural processes. Here, we used high-speed amperometry with enzyme-based substrate-sensitive and control, enzyme-free biosensors to examine second-scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose-containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post-ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra-gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery due to neural activity, intense metabolism, and the influence of ingested glucose reaching the brain. PMID:25393775

Physiology and role of irisin in glucose homeostasis

PubMed Central

Perakakis, Nikolaos; Triantafyllou, Georgios A.; Fernández-Real, José Manuel; Huh, Joo Young; Park, Kyung Hee; Seufert, Jochen; Mantzoros, Christos S.

2018-01-01

Irisin is a myokine that leads to increased energy expenditure by stimulating the ‘browning’ of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned. In this Review, we present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome. PMID:28211512

Galanin regulates blood glucose level in the zebrafish: a morphological and functional study.

PubMed

Podlasz, P; Jakimiuk, A; Chmielewska-Krzesinska, M; Kasica, N; Nowik, N; Kaleczyc, J

2016-01-01

The present study has demonstrated the galaninergic innervation of the endocrine pancreas including sources of the galaninergic nerve fibers, and the influence of galanin receptor agonists on blood glucose level in the zebrafish. For the first time, a very abundant galaninergic innervation of the endocrine pancreas during development is shown, from the second day post-fertilization to adulthood. The fibers originated from ganglia consisting of galanin-IR, non-adrenergic (non-sensory) neurons located rostrally to the pancreatic tissue. The ganglia were found on the dorsal side of the initial part of the anterior intestinal segment, close to the intestinal branch of the vagus nerve. The galanin-IR neurons did not show immunoreactivity for applied antibodies against tyrosine hydroxylase, choline acetyltransferase, and vesicular acetylcholine transporter. Intraperitoneal injections of galanin analog NAX 5055 resulted in a statistically significant increase in the blood glucose level. Injections of another galanin receptor agonist, galnon, also caused a rise in blood glucose level; however, it was not statistically significant. The present findings suggest that, like in mammals, in the zebrafish galanin is involved in the regulation of blood glucose level. However, further studies are needed to elucidate the exact mechanism of the galanin action.

High Amylose White Rice Reduces Post-Prandial Glycemic Response but Not Appetite in Humans

PubMed Central

Zenel, Alison M.; Stewart, Maria L.

2015-01-01

The present study compared the effects of three rice cultivars on postprandial glycemic control and appetite. A single-blind, randomized, crossover clinical trial was performed with 18 healthy subjects, nine males and nine females. Three treatments were administered at three separate study visits: commercially available conventional white rice (short grain), specialty high amylose white rice 1 (Dixiebelle), and specialty high amylose white rice 2 (Rondo). Postprandial capillary blood glucose, venous blood glucose and insulin measurements, and appetite visual analog scale (VAS) surveys were done over the course of two hours. The capillary blood glucose concentrations were significantly lower for Rondo compared to short grain rice at 30 min, and for Dixiebelle and Rondo compared to short grain rice at 45, 60, and 120 min. Capillary blood glucose area under the curve (AUC) was significantly lower for Dixiebelle and Rondo compared to short grain rice. Subjects were significantly more hungry at 30 min after Dixiebelle intake than Rondo intake, but there were no other significant effects in appetite ratings. The present study determined that intake of high amylose rice with resistant starch (RS) can attenuate postprandial blood glucose and insulin response in comparison to short grain rice. PMID:26147654

Performance assessment of a glucose control protocol in septic patients with an automated intermittent plasma glucose monitoring device.

PubMed

Umbrello, M; Salice, V; Spanu, P; Formenti, P; Barassi, A; Melzi d'Eril, G V; Iapichino, G

2014-10-01

The optimal level and modality of glucose control in critically ill patients is still debated. A protocolized approach and the use of nearly-continuous technologies are recommended to manage hyperglycemia, hypoglycemia and glycemic variability. We recently proposed a pato-physiology-based glucose control protocol which takes into account patient glucose/carbohydrate intake and insulin resistance. Aim of the present investigation was to assess the performance of our protocol with an automated intermittent plasma glucose monitoring device (OptiScanner™ 5000). OptiScanner™ was used in 6 septic patients, providing glucose measurement every 15' from a side-port of an indwelling central venous catheter. Target level of glucose was 80-150 mg/dL. Insulin infusion and kcal with nutritional support were also recorded. 6 septic patients were studied for 319 h (1277 measurements); 58 [45-65] hours for each patient (measurements/patient: 231 [172-265]). Blood glucose was at target for 93 [90-98]% of study time. Mean plasma glucose was 126 ± 11 mg/dL. Only 3 hypoglycemic episodes (78, 78, 69 mg/dL) were recorded. Glucose variability was limited: plasma glucose coefficient of variation was 11.7 ± 4.0% and plasma glucose standard deviation was 14.3 ± 5.5 mg/dL. The local glucose control protocol achieved satisfactory glucose control in septic patients along with a high degree of safeness. Automated intermittent plasma glucose monitoring seemed useful to assess the performance of the protocol. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

3beta-taraxerol of Mangifera indica, a PI3K dependent dual activator of glucose transport and glycogen synthesis in 3T3-L1 adipocytes.

PubMed

Sangeetha, Kadapakkam Nandabalan; Sujatha, Sundaresan; Muthusamy, Velusamy Shanmuganathan; Anand, Singaravel; Nithya, Nirmal; Velmurugan, Devadasan; Balakrishnan, Arun; Lakshmi, Baddireddi Subhadra

2010-03-01

The present study focuses on identifying and developing an anti-diabetic molecule from plant sources that would effectively combat insulin resistance through proper channeling of glucose metabolism involving glucose transport and storage. Insulin-stimulated glucose uptake formed the basis for isolation of a bioactive molecule through column chromatography followed by its characterization using NMR and mass spectroscopic analysis. Mechanism of glucose transport and storage was evaluated based on the expression profiling of signaling molecules involved in the process. The study reports (i) the isolation of a bioactive compound 3beta-taraxerol from the ethyl acetate extract (EAE) of the leaves of Mangifera indica (ii) the bioactive compound exhibited insulin-stimulated glucose uptake through translocation and activation of the glucose transporter (GLUT4) in an IRTK and PI3K dependent fashion. (iii) the fate of glucose following insulin-stimulated glucose uptake was ascertained through glycogen synthesis assay that involved the activation of PKB and suppression of GSK3beta. This study demonstrates the dual activity of 3beta-taraxerol and the ethyl acetate extract of Mangifera indica as a glucose transport activator and stimulator of glycogen synthesis. 3beta-taraxerol can be validated as a potent candidate for managing the hyperglycemic state. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Effect of Pterocarpus santalinus bark, on blood glucose, serum lipids, plasma insulin and hepatic carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats.

PubMed

Kondeti, Vinay Kumar; Badri, Kameswara Rao; Maddirala, Dilip Rajasekhar; Thur, Sampath Kumar Mekala; Fatima, Shaik Sameena; Kasetti, Ramesh Babu; Rao, Chippada Appa

2010-05-01

The present study was designed to investigate the effect of bark of Pterocarpus santalinus, an ethnomedicinal plant, on blood glucose, plasma insulin, serum lipids and the activities of hepatic glucose metabolizing enzymes in streptozotocin-induced diabetic rats. Streptozotocin-induced diabetic rats were treated (acute/short-term and long-term) with ethyl acetate:methanol fractions of ethanolic extract of the bark of P. santalinus. Fasting blood glucose, HbA(1C), plasma insulin and protein were estimated before and after the treatment, along with hepatic glycogen, and activities of hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and glucose-6-phosphate dehydrogenase. Further anti-hyperlipidemic activity was studied by measuring the levels of serum lipids and lipoproteins. Phytochemical analysis of active fraction showed the presence of flavonoids, glycosides and phenols. Biological testing of the active fraction demonstrated a significant antidiabetic activity by reducing the elevated blood glucose levels and glycosylated hemoglobin, improving hyperlipidemia and restoring the insulin levels in treated experimental induced diabetic rats. Further elucidation of mechanism of action showed improvement in the hepatic carbohydrate metabolizing enzymes after the treatment. Our present investigation suggests that active fraction of ethanolic extract of bark of P. santalinus decreases streptozotocin induced hyperglycemia by increasing glycolysis and decreasing gluconeogenesis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil and Gas Extraction and Processing Emissions.

PubMed

Rich, Alisa L; Patel, Jay T; Al-Angari, Samiah S

2016-01-01

Carbon disulfide (CS2) has been historically associated with the manufacturing of rayon, cellophane, and carbon tetrachloride production. This study is one of the first to identify elevated atmospheric levels of CS2 above national background levels and its mechanisms to dysregulate normal glucose metabolism. Interference in glucose metabolism can indirectly cause other complications (diabetes, neurodegenerative disease, and retinopathy), which may be preventable if proper precautions are taken. Rich et al found CS2 and 12 associated sulfide compounds present in the atmosphere in residential areas where unconventional shale oil and gas extraction and processing operations were occurring. Ambient atmospheric concentrations of CS2 ranged from 0.7 parts per billion by volume (ppbv) to 103 ppbv over a continuous 24-hour monitoring period. One-hour ambient atmospheric concentrations ranged from 3.4 ppbv to 504.6 ppbv. Using the U.S. Environmental Protection Agency Urban Air Toxic Monitoring Program study as a baseline comparison for atmospheric CS2 concentrations found in this study, it was determined that CS2 atmospheric levels were consistently elevated in areas where unconventional oil and gas extraction and processing occurred. The mechanisms by which CS2 interferes in normal glucose metabolism by dysregulation of the tryptophan metabolism pathway are presented in this study. The literature review found an increased potential for alteration of normal glucose metabolism in viscose rayon occupational workers exposed to CS2. Occupational workers in the energy extraction industry exposed to CS2 and other sulfide compounds may have an increased potential for glucose metabolism interference, which has been an indicator for diabetogenic effect and other related health impacts. The recommendation of this study is for implementation of regular monitoring of blood glucose levels in CS2-exposed populations as a preventative health measure.

Glucose feeding during development aggravates the toxicity of the organophosphorus insecticide Monocrotophos in the nematode, Caenorhabditis elegans.

PubMed

Salim, Chinnu; Rajini, P S

2014-05-28

Several studies have demonstrated that high glucose feeding induced oxidative stress and apoptosis thereby affecting growth, fertility, aging and lifespan in Caenorhabditis elegans. Earlier studies from our laboratory had clearly established the propensity of monocrotophos, an OPI to alter the physiological and behavioral responses of C. elegans. The present study was aimed to investigate the effect of monocrotophos (MCP) on physiological/behavioral and biochemical responses in C. elegans that were maintained on high glucose diet. We exposed the worms through development to high glucose diet (2%) and then treated with sublethal concentrations of MCP (0.5, 0.75, 1.5mM). We measured the behavioral responses in terms of locomotion, physiological responses in terms of egg laying, brood size, lifespan; morphological alterations; and biochemical responses including glucose content. The worms exposed from egg stage through development to high glucose diet showed enhanced toxic outcome of MCP in terms of physiological, behavioral and biochemical responses. Our studies showed that C. elegans is a good model to study glucose-OPI interactive neurotoxicity since all the responses could be studied at ease in this organism and the outcome could be well extrapolated to those that one would expect in higher animals. Copyright © 2014 Elsevier Inc. All rights reserved.

A Robust, Enzyme-Free Glucose Sensor Based on Lysine-Assisted CuO Nanostructures.

PubMed

Baloach, Qurrat-Ul-Ain; Tahira, Aneela; Mallah, Arfana Begum; Abro, Muhammad Ishaq; Uddin, Siraj; Willander, Magnus; Ibupoto, Zafar Hussain

2016-11-14

The production of a nanomaterial with enhanced and desirable electrocatalytic properties is of prime importance, and the commercialization of devices containing these materials is a challenging task. In this study, unique cupric oxide (CuO) nanostructures were synthesized using lysine as a soft template for the evolution of morphology via a rapid and boiled hydrothermal method. The morphology and structure of the synthesized CuO nanomaterial were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. The prepared CuO nanostructures showed high potential for use in the electrocatalytic oxidation of glucose in an alkaline medium. The proposed enzyme-free glucose sensor demonstrated a robust response to glucose with a wide linear range and high sensitivity, selectivity, stability, and reproducibility. To explore its practical feasibility, the glucose content of serum samples was successfully determined using the enzyme-free sensor. An analytical recovery method was used to measure the actual glucose from the serum samples, and the results were satisfactory. Moreover, the presented glucose sensor has high chemical stability and can be reused for repetitive measurements. This study introduces an enzyme-free glucose sensor as an alternative tool for clinical glucose quantification.

A Robust, Enzyme-Free Glucose Sensor Based on Lysine-Assisted CuO Nanostructures

PubMed Central

Baloach, Qurrat-ul-Ain; Tahira, Aneela; Mallah, Arfana Begum; Abro, Muhammad Ishaq; Uddin, Siraj; Willander, Magnus; Ibupoto, Zafar Hussain

2016-01-01

The production of a nanomaterial with enhanced and desirable electrocatalytic properties is of prime importance, and the commercialization of devices containing these materials is a challenging task. In this study, unique cupric oxide (CuO) nanostructures were synthesized using lysine as a soft template for the evolution of morphology via a rapid and boiled hydrothermal method. The morphology and structure of the synthesized CuO nanomaterial were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. The prepared CuO nanostructures showed high potential for use in the electrocatalytic oxidation of glucose in an alkaline medium. The proposed enzyme-free glucose sensor demonstrated a robust response to glucose with a wide linear range and high sensitivity, selectivity, stability, and reproducibility. To explore its practical feasibility, the glucose content of serum samples was successfully determined using the enzyme-free sensor. An analytical recovery method was used to measure the actual glucose from the serum samples, and the results were satisfactory. Moreover, the presented glucose sensor has high chemical stability and can be reused for repetitive measurements. This study introduces an enzyme-free glucose sensor as an alternative tool for clinical glucose quantification. PMID:27854253

Affinity adsorption of glucose degradation products improves the biocompatibility of conventional peritoneal dialysis fluid.

PubMed

Ishikawa, Naoyoshi; Miyata, Toshio; Ueda, Yasuhiko; Inagi, Reiko; Izuhara, Yuko; Yuzawa, Hiroko; Onogi, Hiroshi; Nishina, Makoto; Nangaku, Masaomi; Van Ypersele De Strihou, Charles; Kurokawa, Kiyoshi

2003-01-01

Reactive carbonyl compounds (RCOs) present in peritoneal dialysis (PD) fluid have been incriminated in the progressive deterioration of the peritoneal membrane in long-term PD patients. They are initially present in fresh conventional heat-sterilized glucose PD fluid and are supplemented during dwell time by the diffusion of blood RCOs within the peritoneal cavity. In the present study, RCO entrapping agents were immobilized on affinity beads to adsorb RCOs both in fresh PD fluid and in PD effluent. The RCO trapping potential of various compounds was assessed in vitro first by dissolving them in the tested fluid and subsequently after coupling with either epoxy- or amino-beads. The tested fluids include fresh heat-sterilized glucose and non-glucose PD fluids, and PD effluent. Their RCOs contents, that is, glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG), formaldehyde, 5-hydroxymethylfuraldehyde, acetaldehyde, and 2-furaldehyde were monitored by reverse-phase high-pressure liquid chromatography. The biocompatibility of PD fluid was assessed by a cytotoxic assay with either human epidermoid cell line A431 cells or with primary cultured human peritoneal mesothelial cells. Among the tested RCO entrapping agents, hydrazine coupled to epoxy-beads proved the most efficient. It lowered the concentrations of three dicarbonyl compounds (GO, MGO, and 3-DG) and those of aldehydes present in fresh heat-sterilized glucose PD fluid toward the low levels observed in filter-sterilized glucose PD fluid. It did not change the glucose and electrolytes concentration of the PD fluid but raised its pH from 5.2 to 5.9. Hydrazine-coupled epoxy-bead also lowered the PD effluent content of total RCOs, measured by the 2,4-dinitrophenylhydrazone (DNPH) method. The cytotoxicity of heat-sterilized PD fluid incubated with hydrazine-coupled epoxy-beads was decreased to the level observed in filter-sterilized PD fluid as the result of the raised pH and the lowered RCOs levels. Hydrazine-coupled epoxy-beads reduce the levels of a variety of dicarbonyls and aldehydes present in heat-sterilized glucose PD fluid to those in filter-sterilized PD fluid, without altering glucose, lactate, and electrolytes contents but with a rise in pH. Incubated with PD effluents, it is equally effective in reducing the levels of serum-derived RCOs. RCO entrapping agents immobilized on affinity beads improve in vitro the biocompatibility of conventional heat-sterilized glucose PD fluid. Their clinical applicability requires further studies.

Adiposity associated changes in serum glucose and adiponectin levels modulate ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2018-06-01

The aim of the present study was to evaluate the mechanism by which embryonic development in Cynopterus sphinx is impaired during the period of increased accumulation of white adipose tissue during winter scarcity of food. The change in the mass of white adipose tissue during adipogenesis showed significant positive correlation with the circulating glucose level. But increase in circulating glucose level during the adipogenesis showed negative correlation with circulating progesterone and adiponectin levels. The in vivo study showed increased glucose uptake by the adipose tissue during adipogenesis due to increased expression of insulin receptor (IR) and glucose transporter (GLUT) 4 proteins. This study showed decline in the adiponectin level during fat accumulation. In the in vitro study, ovary treated with high doses of glucose showed impaired progesterone synthesis. This is due to decreased glucose uptake mediated decrease in the expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein, IR, GLUT4 and AdipoR1 proteins. But the ovary treated with adiponectin either alone or with higher concentration of glucose showed improvement in progesterone synthesis due to increased expression of IR, GLUT4 and AdipoR1 mediated increased glucose uptake. In conclusion, increased circulating glucose level prior to winter dormancy preferably transported to white adipose tissue for fat accumulation diverting glucose away from the ovary. Consequently the decreased availability of adiponectin and glucose to the ovary and utero-embryonic unit may be responsible for impaired progesterone synthesis and delayed embryonic development. The delayed embryonic development in Cynopterus sphinx may have evolved, in part, as a mechanism to prevent pregnancy loss during the period of decreased energy availability. Copyright © 2018 Elsevier Inc. All rights reserved.

The effects of glucose ingestion and glucose regulation on memory performance in older adults with mild cognitive impairment.

PubMed

Riby, L M; Marriott, A; Bullock, R; Hancock, J; Smallwood, J; McLaughlin, J

2009-04-01

Previous research investigating the impact of glucose ingestion and/or improvements in glucose regulation has found selective cognitive facilitation on episodic memory tasks in successful ageing and dementia. The present study aimed to extend this research to mild cognitive impairment (MCI). In a repeated-measures design, 24 older adults with and 24 older adults without MCI performed a battery of memory and attention tasks after 25 g of glucose or a sweetness matched placebo. In addition, to assess the impact of individual differences in glucose regulation, blood glucose measurements were taken throughout the testing session. Consistent with previous research, cognitive facilitation was observed for episodic memory tasks only in both successful ageing and MCI. Older adults with MCI had a similar glucose regulatory response as controls but their fasting levels were elevated. Notably, higher levels of blood glucose were associated with impaired memory performance in both the glucose and placebo conditions. Importantly, both blood glucose and memory performance indices were significant predictors of MCI status. The utility of glucose supplementation and the use of glucose regulation as a biological marker are discussed in relation to these data.

Urinary metabolomic profiling in mice with diet-induced obesity and type 2 diabetes mellitus after treatment with metformin, vildagliptin and their combination.

PubMed

Pelantová, Helena; Bugáňová, Martina; Holubová, Martina; Šedivá, Blanka; Zemenová, Jana; Sýkora, David; Kaválková, Petra; Haluzík, Martin; Železná, Blanka; Maletínská, Lenka; Kuneš, Jaroslav; Kuzma, Marek

2016-08-15

Metformin, vildagliptin and their combination are widely used for the treatment of diabetes, but little is known about the metabolic responses to these treatments. In the present study, NMR-based metabolomics was applied to detect changes in the urinary metabolomic profile of a mouse model of diet-induced obesity in response to these treatments. Additionally, standard biochemical parameters and the expression of enzymes involved in glucose and fat metabolism were monitored. Significant correlations were observed between several metabolites (e.g., N-carbamoyl-β-alanine, N1-methyl-4-pyridone-3-carboxamide, N1-methyl-2-pyridone-5-carboxamide, glucose, 3-indoxyl sulfate, dimethylglycine and several acylglycines) and the area under the curve of glucose concentrations during the oral glucose tolerance test. The present study is the first to present N-carbamoyl-β-alanine as a potential marker of type 2 diabetes mellitus and consequently to demonstrate the efficacies of the applied antidiabetic interventions. Moreover, the elevated acetate level observed after vildagliptin administration might reflect increased fatty acid oxidation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The impact of glucose ingestion and gluco-regulatory control on cognitive performance: a comparison of younger and middle aged adults.

PubMed

Meikle, Andrew; Riby, Leigh M; Stollery, Brian

2004-12-01

A great deal of research has been devoted to the issue of whether the ingestion of a glucose containing drink facilitates cognitive performance. However, it remains unclear exactly how age and individual differences in gluco-regulatory control mediate a boost in cognitive functioning. The present study investigates these issues further. A repeated measures (25 g vs 50 g glucose vs placebo) counterbalanced, double-blind design was used with 25 younger and middle-aged adults. A battery of memory and non-memory tasks was administered; including tests of episodic and semantic memory, attention and visuospatial functioning. Glucose ingestion largely facilitated performance on tasks with a memory component. Notably, task demands and age (young vs middle-aged) contributed to the magnitude of memory enhancement. This finding suggests an age- and load-specific benefit of glucose intake. In addition, evidence suggests greater facilitation in individuals with good glucose regulation. These data are discussed in relation to the idea that glucose specifically affects neural mechanisms supporting memory functioning (i.e. the hippocampus), which are known to decline in ageing. Importantly, the present investigation adds to the growing body of literature showing the utility of glucose supplementation as memory enhancers. 2004 John Wiley & Sons, Ltd.

BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

PubMed Central

Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

2012-01-01

Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

Graphene-gold nanoparticle composite: application as a good scaffold for construction of glucose oxidase biosensor.

PubMed

Sabury, Sina; Kazemi, Sayed Habib; Sharif, Farhad

2015-04-01

In the present work we report a facile method for fabrication of glucose oxidase immobilized on the partially reduced graphene-gold nanocomposite (PRGO-AuNPs/GOx) as a novel biosensor for determination of glucose concentration. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to study the morphology of PRGO and PRGO-AuNPs. Also, fast Fourier transformation infrared spectroscopy (FTIR) and UV-Vis spectroscopy were used to confirm formation of graphene and graphene-gold composite. Then, the electrochemical behavior of PRGO-AuNPs/GOx modified electrode was studied by cyclic voltammetry (CV). Our electrochemical studies, especially chronoamperometry (CA), showed that the PRGO-AuNPs/GOx modified electrode has excellent electrocatalytic activity towards the glucose. The limit of detection and sensitivity towards glucose were estimated as 0.06μM and 15.04mAmM(-1), respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of glutathione S-transferase M1 and T1 polymorphisms on blood pressure, blood glucose, and lipid profiles following the supplementation of kale (Brassica oleracea acephala) juice in South Korean subclinical hypertensive patients.

PubMed

Han, Jeong-Hwa; Lee, Hye-Jin; Kim, Tae-Seok; Kang, Myung-Hee

2015-02-01

Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. This study examines whether daily supplementation of kale juice can modulate blood pressure (BP), levels of lipid profiles, and blood glucose, and whether this modulation could be affected by the GSTM1 and GSTT1 polymorphisms. 84 subclinical hypertensive patients showing systolic BP over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were collected on 0-week and 6-week in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol) and blood glucose. Systolic and diastolic blood pressure was significantly decreased in all patients regardless of their GSTM1 or GSTT1 polymorphisms after kale juice supplementation. Blood glucose level was decreased only in the GSTM1-present genotype, and plasma lipid profiles showed no difference in both the GSTM1-null and GSTM1-present genotypes. In the case of GSTT1, on the other hand, plasma HDL-C was increased and LDL-C was decreased only in the GSTT1-present type, while blood glucose was decreased only in the GSTT1-null genotype. These findings suggest that the supplementation of kale juice affected blood pressure, lipid profiles, and blood glucose in subclinical hypertensive patients depending on their GST genetic polymorphisms, and the improvement of lipid profiles was mainly greater in the GSTT1-present genotype and the decrease of blood glucose was greater in the GSTM1-present or GSTT1-null genotypes.

A paper strip based non-invasive glucose biosensor for salivary analysis.

PubMed

Soni, Anuradha; Jha, Sandeep Kumar

2015-05-15

In our present study, we developed an optical biosensor for direct determination of salivary glucose by using immobilized glucose oxidase enzyme on filter paper strip (specific activity 1.4 U/strip) and then reacting it with synthetic glucose samples in presence of co-immobilized color pH indicator. The filter paper changed color based on concentration of glucose in reaction media and hence, by scanning this color change (using RGB profiling) through an office scanner and open source image processing software (GIMP) the concentration of glucose in the reaction medium could be deduced. Once the biosensor was standardized, the synthetic glucose sample was replaced with human saliva from donors. The individual's blood glucose level at the time of obtaining saliva was also measured using an Accuchek(™) active glucometer (Roche Inc.). In this preliminary study, a correlation of nearly 0.64 was found between glucose levels in saliva and blood of healthy individuals and in diabetic patients it was nearly in the order of 0.95, thereby validating the importance of salivary analysis. The RGB profiling method obtained a detection range of 9-1350 mg/dL glucose at a response time of 45 s and LOD of 22.2 mg/dL. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

NASA Astrophysics Data System (ADS)

Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

2017-12-01

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations.

PubMed

Ng, Tzu Shan; Desa, Mohd Nasir Mohd; Sandai, Doblin; Chong, Pei Pei; Than, Leslie Thian Lung

2016-06-01

Glucose is an important fuel source to support many living organisms. Its importance in the physiological fitness and pathogenicity of Candida glabrata, an emerging human fungal pathogen has not been extensively studied. The present study aimed to investigate the effects of glucose on the growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of C. glabrata. In addition, its effect on the expression of a putative high affinity glucose sensor gene, SNF3 was also investigated. Glucose concentrations were found to exert effects on the physiological responses of C. glabrata. The growth rate of the species correlated positively to the amount of glucose. In addition, low glucose environments were found to induce C. glabrata to form biofilm and resist amphotericin B. Conversely, high glucose environments promoted oxidative stress resistance of C. glabrata. The expression of CgSNF3 was found to be significantly up-regulated in low glucose environments. The expression of SNF3 gene in clinical isolates was found to be higher compared to ATCC laboratory strains in low glucose concentrations, which may explain the better survivability of clinical isolates in the low glucose environment. These observations demonstrated the impact of glucose in directing the physiology and virulence fitness of C. glabrata through the possible modulation by SNF3 as a glucose sensor, which in turn aids the species to adapt, survive and thrive in hostile host environment. Copyright © 2015 Elsevier B.V. All rights reserved.

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects

PubMed Central

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

Objective: The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. Methods: This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. Results: A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. Conclusion: The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol. PMID:26430445

Significant association of serum creatinine with HbA1C in impaired glucose tolerant Pakistani subjects.

PubMed

Farasat, Tasnim; Sharif, Saima; Naz, Shagufta; Fazal, Sabiha

2015-01-01

The present study was conducted to assess the serum concentration of creatinine and determine its relationship with potential risk factors of diabetes in Impaired Glucose tolerance subjects. This cross sectional study was conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore from January 2011- June 2011. Patients with age group 34-67 years, (both sexes) were included in the study. Different demographic parameters as age, BMI, WHR, B.P, personal history and socioeconomic status were recorded. Oral Glucose Tolerance Test was performed. The biochemical parameters including HbA1c, lipid profile, urea, uric acid, creatinine and bilirubin level were measured by chemistry analyzer. A strong correlation between creatinine and HbA1c was observed. The level of creatinine was also significantly associated with age in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL-Chol and TG while negatively significantly associated with BMI, fasting blood glucose and HDL-Chol. The present study concluded significant association of serum creatinine with HbA1c, BMI and HDL cholesterol.

Antihyperglycemic activity of Piper betle leaf on streptozotocin-induced diabetic rats.

PubMed

Santhakumari, P; Prakasam, A; Pugalendi, K V

2006-01-01

Piper betle, an indigenous medicinal plant, has a folk (Siddha and Ayurvedha) reputation in the rural southern India. The present study was carried out to evaluate the effect of P. betle on glucose metabolism since it is consumed as betel-quid after meals. Plasma levels of glucose and glycosylated hemoglobin and activities of liver hexokinase and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase in control and streptozotocin (STZ) diabetic rats were assayed. Oral administration of leaf suspension of P. betle (75 and 150 mg/kg of body weight) for 30 days resulted in significant reduction in blood glucose (from 205.00 +/- 10.80 mg/dL to 151.30 +/- 6.53 mg/dL) and glycosylated hemoglobin and decreased activities of liver glucose-6-phosphatase and fructose-1,6-bisphosphatase, while liver hexokinase increased (P < .05), in STZ diabetic rats when compared with untreated diabetic rats. P. betle at a dose of 75 mg/kg of body weight exhibited better sugar reduction than 150 mg/kg of body weight. In addition, protection against body weight loss of diabetic animals was also observed. The effects produced by P. betle were compared with the standard drug glibenclamide. Thus, the present study clearly shows that P. betle intake influences glucose metabolism beneficially.

Vitamin K2 Improves Anxiety and Depression but not Cognition in Rats with Metabolic Syndrome: a Role of Blood Glucose?

PubMed

Gancheva, Silvia M; Zhelyazkova-Savova, Maria D

2016-12-01

The metabolic syndrome is a socially important disorder of energy utilization and storage, recognized as a factor predisposing to the development of depression, anxiety and cognitive impairment in humans. In the present study we examined the effects of vitamin K2 on the behavior of rats with metabolic syndrome and looked for relationships with the effects on blood sugar. Male Wistar rats were divided in four groups: a control group on a regular rat chow, a metabolic syndrome (MS) group fed a high-fat high-fructose diet, a control group treated with vitamin K2 and a MS group treated with vitamin K2. Vitamin K2 was given by gavage. At the end of the study (after 10 weeks) behavioral tests were performed and fasting blood glucose was measured. Anxiety was determined using the social interaction test and depression was assessed by the Porsolt test. Memory effects were estimated by the object recognition test. Correlations between fasting blood glucose and behavioral performance were analyzed. The rats from the MS group had elevated blood glucose. They had anxiety, depression and memory deficit. Vitamin K2 normalized blood glucose, reduced anxiety and depression, but did not improve memory. Time of social interaction (inverse index of anxiety) and memory recognition were negatively correlated with blood glucose in the untreated rats but the immobility time (measure of depression) was not. When vitamin K2-treated rats were added, the correlation of blood glucose with the time of social interaction was kept, but the one with the recognition memory was lost. It might be that the anxiolytic effect of vitamin K2 in this setting is at least partly due to its effects on blood glucose, while the anti-depressant effect is glucose-independent. The present study demonstrated that vitamin K2 prevented the development of anxiety and depression, but did not improve the memory deficit caused by the dietary manipulation in an experimental model of metabolic syndrome. It might be that the anxiolytic effect of vitamin K2 is at least partly due to its effects on blood glucose, while the antidepressant effect is glucose-independent.

Follow-up of blood glucose distribution characteristics in a health examination population in Chengdu from 2010 to 2016

PubMed Central

Wang, Yuting; Xu, Wangdong; Zhang, Qiongying; Bao, Ting; Yang, Hanwei; Huang, Wenxia; Tang, Huairong

2018-01-01

Abstract The worldwide prevalence and incidence of diabetes and obesity are increasing in pandemic proportions. Thus, regular health examination is an important way for early detection of diabetes and glucose intolerance. The present study aims to detect the blood glucose distribution characteristics of the participants in the Health Examination Center at West China Hospital, Sichuan University from 2010 to 2016. A prospective cohort included 9168 Chinese participants, aged 18 years or more, who had available information on fasting blood glucose concentrations at the start of the study (2010). Examination surveys were conducted every year from 2010 to 2016. Cases having serum level of fasting blood glucose between 2.2 and 6.1 mmol/L were considered as normality, while serum level of fasting blood glucose < 2.2 or higher than 6.2 mmol/L were considered as abnormality. The percentage of participants having normal level of glucose was gradually reduced both in males and females from 2010 to 2016, by which the percentage of males having normal level of glucose was significantly lower than that in females. Moreover, the mean level of glucose was significantly increased from 2010 to 2016 both in males and females overall, and the mean level of glucose was higher in males compared with that in females every year. Furthermore, we showed that the level of glucose was gradually increased year by year in each age group, and the level of glucose was higher in aged cases compared with the young population. The study population in the current study showed higher levels of glucose with ages increasing, and males indicated higher expression of glucose than that in females. Some preventive action may be adopted early and more attention can be paid to this health-examination population. PMID:29465557

Parsing glucose entry into the brain: novel findings obtained with enzyme-based glucose biosensors.

PubMed

Kiyatkin, Eugene A; Wakabayashi, Ken T

2015-01-21

Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between "active" and "passive" glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the "neuronal" hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism.

Safety and accuracy of a new long-term subconjunctival glucose sensor.

PubMed

Hasslacher, Christoph; Auffarth, Gerd; Platten, Isabell; Rabsilber, Tanja; Smith, Beate; Kulozik, Felix; Knuth, Monika; Nikolaus, Katharina; Müller, Achim

2012-09-01

A new biosensor has been developed by EyeSense (Großostheim, Germany) that is placed into the conjunctiva of one eye to measure the glucose concentration of the surrounding tissue in a non-invasive manner. In the present study we investigated the correlation between glucose concentrations measured by the EyeSense implant and those determined by finger prick testing, as well as the tolerability and safety of the implant over a 16-week period. The study was performed in 28 diabetic patients. The biosensor was inserted under local anesthesia and sterile conditions. Correlations between capillary glucose measured by laboratory methods and interstitial glucose determined by the biosensor were investigated by inducing increases and decreases in glucose values between 60 and 300 mg/dL. Most patients experienced a mild subconjunctival hemorrhage postoperatively. Except for the minor sensation of the presence of foreign body, the implants were well tolerated. Three patients lost the ocular mini insert spontaneously, whereas there was a function failure of the insert in four patients. Error grid analysis showed that the percentage of data pairs in the acceptable ranges (zone A and B) was very high (>96%). However, there was a shift from zone A to zone B during observation. This was due primarily to an increase in the lag time between capillary and interstitial measured glucose. he present study demonstrates good tolerability and measurement performance of the biosensor. The reasons for an increase in the lag time are still unknown; local reactions may be involved. © 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Fluctuations in nucleus accumbens extracellular glutamate and glucose during motivated glucose-drinking behavior: dissecting the neurochemistry of reward.

PubMed

Wakabayashi, Ken T; Myal, Stephanie E; Kiyatkin, Eugene A

2015-02-01

While motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain's excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward-related neural processes. Here, we used high-speed amperometry with enzyme-based substrate-sensitive and control, enzyme-free biosensors to examine second-scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose-containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post-ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra-gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery because of neural activity, intense metabolism, and the influence of ingested glucose reaching the brain. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Acute effects of repeated bouts of aerobic exercise on arterial stiffness after glucose ingestion.

PubMed

Kobayashi, Ryota; Hashimoto, Yuto; Hatakeyama, Hiroyuki; Okamoto, Takanobu

2018-03-22

The aim of this study was to investigate the acute repeated bouts of aerobic exercise decrease leg arterial stiffness. However, the influence of repeated bouts of aerobic exercise on arterial stiffness after glucose ingestion is unknown. The present study investigates the acute effects of repeated bouts of aerobic exercise on arterial stiffness after the 75-g oral glucose tolerance test (OGTT). Ten healthy young men (age, 23.2 ± 0.9 years) performed repeated bouts of aerobic exercise trial (RE, 65% peak oxygen uptake; two 15 min bouts of cycling performed 20 min apart) and control trial (CON, seated and resting in a quiet room) at 80 min before the 75-g OGTT on separate days in a randomized, controlled crossover fashion. Carotid-femoral (aortic) and femoral-ankle (leg) pulse wave velocity, carotid augmentation index, brachial and ankle blood pressure, heart rate and blood glucose and insulin levels were measured before (baseline) and 30, 60 and 120 min after the 75-g OGTT. Leg pulse wave velocity, ankle systolic blood pressure and blood glucose levels increased from baseline after the 75-g OGTT in the CON trial, but not in the RE trial. The present findings indicate that acute repeated bouts of aerobic exercise before glucose ingestion suppress increases in leg arterial stiffness following glucose ingestion. RE trial repeated bouts of aerobic exercise trial; CON trial control trial; BG blood glucose; VO 2peak peak oxygen uptake; PWV Pulse wave velocity; AIx carotid augmentation index; BP blood pressure; HR heart rate; CVs coefficients of variation; RPE Ratings of perceived exertion; SE standard error.

Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake.

PubMed

Pitkanen, O P; Laine, H; Kemppainen, J; Eronen, E; Alanen, A; Raitakari, M; Kirvela, O; Ruotsalainen, U; Knuuti, J; Koivisto, V A; Nuutila, P

1999-12-15

1. The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be ideal to determine whether the vasoactive agent affects flow distribution or only increases the mean flow. 2. In the present study blood flow, flow distribution and glucose uptake were measured simultaneously in both legs of 10 healthy men (aged 29 +/- 1 years, body mass index 24 +/- 1 kg m-2) using positron emission tomography (PET) combined with [15O]H2O and [18F]fluoro-2-deoxy-D-glucose (FDG). The role of blood flow in muscle glucose uptake was studied by increasing blood flow in one leg with sodium nitroprusside (SNP) and measuring glucose uptake simultaneously in both legs during euglycaemic hyperinsulinaemia (insulin infusion 6 pmol kg-1 min-1). 3. SNP infusion increased skeletal muscle blood flow by 86 % (P < 0.01), but skeletal muscle flow distribution and insulin-stimulated glucose uptake (61.4 +/- 7. 5 vs. 67.0 +/- 7.5 micromol kg-1 min-1, control vs. SNP infused leg, not significant), as well as flow distribution between different tissues of the femoral region, remained unchanged. The effect of SNP infusion on blood flow and distribution were unchanged during infusion of physiological levels of insulin (duration, 150 min). 4. Despite a significant increase in mean blood flow induced by an intra-arterial infusion of SNP, glucose uptake and flow distribution remained unchanged in resting muscles of healthy subjects. These findings suggest that SNP, an endothelium-independent vasodilator, increases non-nutritive, but not nutritive flow or capillary recruitment.

Effect of Alpinia calcarata on glucose uptake in diabetic rats-an in vitro and in vivo model

PubMed Central

2014-01-01

Background Diabetes mellitus is a heterogeneous metabolic disorders characterized by abnormally high levels of blood glucose The main objective of the present work is to study the effect of Alpinia calcarata on glucose uptake in streptozotocin (STZ) induced diabetic rats. Methods The diabetes was induced by single dose of STZ (45 mg/kg) in citrate buffer, while the normal control group was given the vehicle (citrate buffer) only. After induction of diabetes, the diabetic animals were treated with ethanolic extract of Alpinia calcarata (200 mg/kg) and glibenclamide (2 mg/kg) for 30 days. Blood glucose estimation was performed every week of the study. At the end of study period, animals were sacrificed for biochemical studies. Results Streptozotocin induced diabetic rats shows the altered levels of various biochemical profiles. Those levels were brought back to near normal upon treatment with ethanolic extract of Alpinia calcarata and standard drug glibanclamide. No significant changes were observed on treatment with plant extract alone group indicated that there are no toxic substances present in Alpinia calcarata. The antidiabetic activity of plant extract was also further confirmed by histopathological studies. The ethanolic extract of Alpinia calcarata shows significant inhibition of alpha glucosidase activity and also enhancing the glucose uptake in rat hemidiaphragm. Conclusions In conclusion, the ethanolic extract of Alpinia calcarata ameliorates the condition associated with diabetes. PMID:24502532

Simultaneous glucose and xylose uptake by an acetone/butanol/ethanol producing laboratory Clostridium beijerinckii strain SE-2.

PubMed

Zhang, Jie; Zhu, Wen; Xu, Haipeng; Li, Yan; Hua, Dongliang; Jin, Fuqiang; Gao, Mintian; Zhang, Xiaodong

2016-04-01

Most butanol-producing strains of Clostridium prefer glucose over xylose, leading to a slower butanol production from lignocellulose hydrolysates. It is therefore beneficial to find and use a strain that can simultaneously use both glucose and xylose. Clostridium beijerinckii SE-2 strain assimilated glucose and xylose simultaneously and produced ABE (acetone/butanol/ethanol). The classic diauxic growth behavior was not seen. Similar rates of sugar consumption (4.44 mM glucose h(-1) and 6.66 mM xylose h(-1)) were observed suggesting this strain could use either glucose or xylose as the substrate and it has a similar capability to degrade these two sugars. With different initial glucose:xylose ratios, glucose and xylose were consumed simultaneously at rates roughly proportional to their individual concentrations in the medium, leading to complete utilization of both sugars at the same time. ABE production profiles were similar on different substrates. Transcriptional studies on the effect of glucose and xylose supplementation, however, suggests a clear glucose inhibition on xylose metabolism-related genes is still present.

Second generation biofuels: Thermochemistry of glucose and fructose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osmont, A.; Catoire, L.; C.N.R.S. - I.N.S.I.S., I.C.A.R.E., 1C, Avenue de la Recherche Scientifique, 45071 Orleans Cedex 2

2010-06-15

The energetic conversion of biomass into syngas or biogas is a more and more important topic. In the framework of these studies, improved understanding of glucose and fructose thermal decomposition and oxidation appears crucial. For this task, thermodynamic data are needed to make possible, for instance, the building of a detailed chemical kinetic model of glucose and fructose reactivity at high temperature. A semitheoretical protocol, presented elsewhere, is used for the estimation of the thermodynamic data of glucose and fructose in the gas phase. Five isomers of glucose and five isomers of fructose are considered and the lowest-energy conformers aremore » found to be {beta}-D-glucopyranose for glucose and {beta}-D-fructopyranose for fructose. The data for all 10 isomers are provided in the CHEMKIN-NASA format. (author)« less

Assessment of glycemic potential ofMusa paradisiaca stem juice.

PubMed

Singh, Santosh Kumar; Kesari, Achyut Narayan; Rai, Prashant Kumar; Watal, Geeta

2007-09-01

The present study reveals the effect of Musa paradisiaca stem juice on blood glucose level (BGL) of normal & diabetic rats. The dose of 500 mg/kg bodyweight produces a significant rise of 28.3% in blood glucose level after 6h of oral administration in normal rats. Whereas, in sub diabetic rats the same dose produces a rise of 16.4% in blood glucose levels within 1h during glucose tolerance test (GTT) and a rise of 16% after 4 h in fasting blood glucose levels of severe diabetic cases. These results were unexpected and important to report as other species of Musa like Musa sapientum has been reported for its hypoglycemic effect.

Introduction of a Novel Smartphone-Coupled Blood Glucose Monitoring System

PubMed Central

Jendrike, Nina; Baumstark, Annette; Chen, Chieh-Hsiao; Rittmeyer, Delia; Haug, Cornelia; Freckmann, Guido

2017-01-01

The novel system for self-monitoring of blood glucose (SMBG) PixoTest couples SMBG to a smartphone and does not require a separate glucose meter. The integrated system includes all components necessary for a glucose measurement, and owing to a colorimetric measurement principle, a smartphone camera can capture color changes and a software app calculates the corresponding glucose value. In the presented study, the system was evaluated in terms of system accuracy as described in ISO 15197:2013. It was shown to fulfill system accuracy requirements with 97-99% of results from three different reagent system lots within the accuracy limits and 100% of results within zone A of the consensus error grid. PMID:28459160

Noninvasive glucose sensing by transcutaneous Raman spectroscopy

NASA Astrophysics Data System (ADS)

Shih, Wei-Chuan; Bechtel, Kate L.; Rebec, Mihailo V.

2015-05-01

We present the development of a transcutaneous Raman spectroscopy system and analysis algorithm for noninvasive glucose sensing. The instrument and algorithm were tested in a preclinical study in which a dog model was used. To achieve a robust glucose test system, the blood levels were clamped for periods of up to 45 min. Glucose clamping and rise/fall patterns have been achieved by injecting glucose and insulin into the ear veins of the dog. Venous blood samples were drawn every 5 min and a plasma glucose concentration was obtained and used to maintain the clamps, to build the calibration model, and to evaluate the performance of the system. We evaluated the utility of the simultaneously acquired Raman spectra to be used to determine the plasma glucose values during the 8-h experiment. We obtained prediction errors in the range of ˜1.5-2 mM. These were in-line with a best-case theoretical estimate considering the limitations of the signal-to-noise ratio estimates. As expected, the transition regions of the clamp study produced larger predictive errors than the stable regions. This is related to the divergence of the interstitial fluid (ISF) and plasma glucose values during those periods. Two key contributors to error beside the ISF/plasma difference were photobleaching and detector drift. The study demonstrated the potential of Raman spectroscopy in noninvasive applications and provides areas where the technology can be improved in future studies.

Noninvasive glucose sensing by transcutaneous Raman spectroscopy.

PubMed

Shih, Wei-Chuan; Bechtel, Kate L; Rebec, Mihailo V

2015-05-01

We present the development of a transcutaneous Raman spectroscopy system and analysis algorithm for noninvasive glucose sensing. The instrument and algorithm were tested in a preclinical study in which a dog model was used. To achieve a robust glucose test system, the blood levels were clamped for periods of up to 45 min. Glucose clamping and rise/fall patterns have been achieved by injecting glucose and insulin into the ear veins of the dog. Venous blood samples were drawn every 5 min and a plasma glucose concentration was obtained and used to maintain the clamps, to build the calibration model, and to evaluate the performance of the system. We evaluated the utility of the simultaneously acquired Raman spectra to be used to determine the plasma glucose values during the 8-h experiment. We obtained prediction errors in the range of ~1.5-2  mM. These were in-line with a best-case theoretical estimate considering the limitations of the signal-to-noise ratio estimates. As expected, the transition regions of the clamp study produced larger predictive errors than the stable regions. This is related to the divergence of the interstitial fluid (ISF) and plasma glucose values during those periods. Two key contributors to error beside the ISF/plasma difference were photobleaching and detector drift. The study demonstrated the potential of Raman spectroscopy in noninvasive applications and provides areas where the technology can be improved in future studies.

"Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents.

PubMed

Srivastava, Rohit; Jayant, Rahul Dev; Chaudhary, Ayesha; McShane, Michael J

2011-01-01

Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres. The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation. The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site. The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity. © 2010 Diabetes Technology Society.

Implantable fluorescence-based glucose sensor development

NASA Astrophysics Data System (ADS)

Ibey, Bennett L.; Yadavalli, Vamsi K.; Thomas, Hope R.; Rounds, Rebecca M.; Pishko, Michael V.; Cote, Gerard L.

2005-03-01

An implantable sensor is being created that allows measurement of blood glucose through fluorescent detection of an embedded chemical assay. The sensor is based on the competitive binding reaction between the protein Concanavalin A and various saccharide molecules, specifically a glycodendrimer and glucose. Previous studies have shown the ability of an embedded chemical assay using Con A and dextran with shorter wavelength dyes to both sense changes in glucose and generate sufficient fluorescent emission to pass through the dermal tissue. However, due to the chemical constituents of the assay, multivalent binding was evident resulting in poor spectral change due to glucose within the biological range. Use of a glycodendrimer and longer wavelength dyes has improved the sensor"s spectral change due to glucose and the overall signal to noise ratio of the sensor. In this work, a description of this sensor and the results obtained from it will be presented showing a large dynamic range of fluorescence with glucose.

Fasting Glucose and Glucose Tolerance as Potential Predictors of Neurocognitive Function among Non-diabetic Older Adults

PubMed Central

Levy, Shellie-Anne T.; Katzel, Leslie I.; Rosenberger, William F.; Manukyan, Zorayr; Whitfield, Keith E.; Waldstein, Shari R.

2015-01-01

Introduction Significant evidence has demonstrated that Type 2 diabetes mellitus and related pre-cursors are associated with diminished neurocognitive function and risk of dementia among older adults. However, very little research has examined relations of glucose regulation to neurocognitive function among older adults free of these conditions. The primary aim of this investigation was to examine associations among fasting glucose, glucose tolerance, and neurocognitive function among non-diabetic older adults. The secondary aim was to examine age, gender, and education as potential effect modifiers. Methods The study employed a cross-sectional, correlational study design. Participants were 172 older adults with a mean age of 64.43 years (SD = 13.09). The sample was 58% male and 87% White. Participants completed an oral glucose tolerance test as part of a larger study. Trained psychometricians administered neuropsychological tests that assessed performance in the domains of response inhibition, nonverbal memory, verbal memory, attention and working memory, visuoconstructional abilities, visuospatial abilities, psychomotor speed and executive function, and motor speed and manual dexterity. Linear multiple regressions were run to test study aims. Results No significant main effects of fasting glucose and 2-hour glucose emerged for performance on any neurocognitive test; however, significant interactions were present. Higher fasting glucose was associated with poorer short-term verbal memory performance among men, but unexpectedly better response inhibition and long-term verbal memory performance for participants over age 70. Higher 2-hour glucose values were associated with reduced divided attention performance among participants with less than a high school education. Conclusions Mixed findings suggest that glucose levels may be both beneficial and deleterious to neurocognition among non-diabetic older adults. Additional studies with healthy older adults are needed to confirm this unexpected pattern of associations; however, findings have implications for the importance of maintaining healthy glucose levels in older adulthood. PMID:25562529

Ablation of ghrelin O-acyltransferase does not improve glucose intolerance or body adiposity in mice on a leptin-deficient ob/ob background.

PubMed

Kirchner, Henriette; Heppner, Kristy M; Holland, Jenna; Kabra, Dhiraj; Tschöp, Matthias H; Pfluger, Paul T

2013-01-01

Type 2 Diabetes is a global health burden and based on current estimates will become an even larger problem in the future. Developing new strategies to prevent and treat diabetes is a scientific challenge of high priority. The stomach hormone ghrelin has been associated with playing a role in the regulation of glucose homeostasis. However, its precise mechanism and impact on whole glucose metabolism remains to be elucidated. This study aims to clarify the role of the two ghrelin isoforms acyl- and desacyl ghrelin in regulating glucose homeostasis. Therefore ghrelin activating enzyme Ghrelin-O-acyltransferase (GOAT) was ablated in leptin-deficient ob/ob mice to study whether specific acyl ghrelin deficiency or desacyl ghrelin abundance modifies glucose tolerance on a massively obese background. As targeted deletion of acyl ghrelin does not improve glucose homeostasis in our GOAT-ob/ob mouse model we conclude that neither acyl ghrelin nor the increased ratio of desacyl/acyl ghrelin is crucial for controlling glucose homeostasis in the here presented model of massive obesity induced by leptin deficiency.

Repaglinide, but not nateglinide administered supraspinally and spinally exerts an anti-diabetic action in d-glucose fed and streptozotocin-treated mouse models.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

2013-12-01

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

Repaglinide, but Not Nateglinide Administered Supraspinally and Spinally Exerts an Anti-Diabetic Action in D-Glucose Fed and Streptozotocin-Treated Mouse Models

PubMed Central

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi

2013-01-01

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models. PMID:24381497

Acute, but not Chronic, Exposure to Arsenic Provokes Glucose Intolerance in Rats: Possible Roles for Oxidative Stress and the Adrenergic Pathway.

PubMed

Rezaei, Mohsen; Khodayar, Mohammd Javad; Seydi, Enayatollah; Soheila, Alboghobeish; Parsi, Isa Kazemzadeh

2017-06-01

Health problems due to heavy metals have become a worldwide concern. Along with its carcinogenicity, arsenic exposure results in impairment of glucose metabolism and insulin secretion as well as altered gene expression and signal transduction. However, the exact mechanism behind the behaviour of arsenic on glucose homeostasis and insulin secretion has not yet been fully understood. Fasting blood sugar and glucose tolerance tests were evaluated. In this study, we demonstrated that arsenic, when acutely administered, induced glucose intolerance in rats, although its chronic oral exposure did not provoke any glucose intolerance or hyperglycemia in rats. The protective activity of N-acetylcysteine, carvedilol and propranolol in male rats exposed to arsenic were also assessed, and N-acetylcysteine, particularly at 40 and 80 mg/kg, prevented the glucose intolerance induced in rats by arsenic. The present study showed that acute, but not chronic, contact with arsenic generates significant changes in the normal glucose tolerance pattern that may be due fundamentally to overproduction of reactive oxygen species and oxidative stress and is preventable by using N-acetylcysteine, a thiol-containing antioxidant. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2015-03-01

The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats

PubMed Central

Intapad, Suttira; Dasinger, John Henry; Brown, Andrew D.; Fahling, Joel M.; Esters, Joyee; Alexander, Barbara T.

2015-01-01

Background The incidence of metabolic disease increases in early menopause. Low birth weight influences the age at menopause. Thus, this study tested the hypothesis that intrauterine growth restriction programs early reproductive aging and impaired glucose homeostasis in female rats. Methods Estrous cyclicity, body composition, and glucose homeostasis were determined in female control and growth-restricted rats at 6 and 12 months of age; sex steroids at 12 months. Results Glucose intolerance was present at 6 months of age prior to cessation of estrous cyclicity and increased adiposity in female growth-restricted rats. However, female growth-restricted rats exhibited persistent estrus and a significant increase in adiposity, fasting glucose and testosterone at 12 months of age (P<0.05). Insulin release in response to a glucose challenge was blunted in conjunction with a reduction in protein expression of pancreatic glucose transporter type 2 and estrogen receptor alpha at 12 months of age in female growth-restricted rats (P<0.05). Conclusion This study demonstrated that slow fetal growth programmed glucose intolerance that developed prior to early estrous acyclicity; yet, fasting glucose levels were elevated in conjunction with increased adiposity, accelerated cessation of estrous cyclicity and a shift towards testosterone excess at 12 months of age in female growth-restricted rats. PMID:26854801

Parsing Glucose Entry into the Brain: Novel Findings Obtained with Enzyme-Based Glucose Biosensors

PubMed Central

2015-01-01

Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between “active” and “passive” glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the “neuronal” hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism. PMID:25490002

Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose

PubMed Central

Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H.

2016-01-01

A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24 hours and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24 hour time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus. PMID:27473896

Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose.

PubMed

Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H

2016-10-01

A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24h and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24h time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus. Copyright © 2016 Elsevier B.V. All rights reserved.

An artificial pancreas provided a novel model of blood glucose level variability in beagles.

PubMed

Munekage, Masaya; Yatabe, Tomoaki; Kitagawa, Hiroyuki; Takezaki, Yuka; Tamura, Takahiko; Namikawa, Tsutomu; Hanazaki, Kazuhiro

2015-12-01

Although the effects on prognosis of blood glucose level variability have gained increasing attention, it is unclear whether blood glucose level variability itself or the manifestation of pathological conditions that worsen prognosis. Then, previous reports have not been published on variability models of perioperative blood glucose levels. The aim of this study is to establish a novel variability model of blood glucose concentration using an artificial pancreas. We maintained six healthy, male beagles. After anesthesia induction, a 20-G venous catheter was inserted in the right femoral vein and an artificial pancreas (STG-22, Nikkiso Co. Ltd., Tokyo, Japan) was connected for continuous blood glucose monitoring and glucose management. After achieving muscle relaxation, total pancreatectomy was performed. After 1 h of stabilization, automatic blood glucose control was initiated using the artificial pancreas. Blood glucose level varied for 8 h, alternating between the target blood glucose values of 170 and 70 mg/dL. Eight hours later, the experiment was concluded. Total pancreatectomy was performed for 62 ± 13 min. Blood glucose swings were achieved 9.8 ± 2.3 times. The average blood glucose level was 128.1 ± 5.1 mg/dL with an SD of 44.6 ± 3.9 mg/dL. The potassium levels after stabilization and at the end of the experiment were 3.5 ± 0.3 and 3.1 ± 0.5 mmol/L, respectively. In conclusion, the results of the present study demonstrated that an artificial pancreas contributed to the establishment of a novel variability model of blood glucose levels in beagles.

Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

PubMed

McDougal, David H; Hermann, Gerlinda E; Rogers, Richard C

2013-01-01

Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST) in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

Blood glucose control for patients with acute coronary syndromes in Qatar.

PubMed

Wilby, Kyle John; Elmekaty, Eman; Abdallah, Ibtihal; Habra, Masa; Al-Siyabi, Khalid

2016-01-01

Blood glucose is known to be elevated in patients presenting with acute coronary syndromes. However a gap in knowledge exists regarding effective management strategies once admitted to acute care units. It is also unknown what factors (if any) predict elevated glucose values during initial presentation. OBJECTIVES of the study were to characterize blood glucose control in patients admitted to the cardiac care unit (CCU) in Qatar and to determine predictive factors associated with high glucose levels (>10 mmol/l) on admission to the CCU. All data for this study were obtained from the CCU at Heart Hospital in Doha, Qatar. A retrospective chart review was completed for patients admitted to the CCU in Qatar from October 1st, 2012 to March 31st, 2013, of which 283 were included. Baseline characteristics (age, gender, nationality, medical history, smoking status, type of acute coronary syndrome), capillary and lab blood glucose measurements, and use of insulin were extracted. Time spent in glucose ranges of <4, 4 to <8, 8 to <10, and >10 mmol/1 was calculated manually. Univariate and multivariate logistic regression were performed to assess factors associated with high glucose on admission. The primary analysis was completed with capillary data and a sensitivity analysis was completed using laboratory data. Blood glucose values measured on admission and throughout length of stay in the CCU. Capillary blood glucose data showed majority of time was spent in the range of >10 mmol/l (41.95%), followed by 4-8 mmol/l (35.44%), then 8-10 mmol/l (21.45%), and finally <4 mmol/l (1.16%). As a sensitivity analysis, laboratory data showed very similar findings. Diabetes, hypertension, and non-smoker status predicted glucose values >10 mmol/l on admission (p < 0.05) in a univariate analysis but only diabetes remained significant in a multivariate model (OR 23.3; 95% CI, 11.5-47.3). Diabetes predicts high glucose values on hospital admission for patients with ACS and patients are not being adequately controlled throughout CCU stay.

Fabrication of a liquid-gated enzyme field effect device for sensitive glucose detection.

PubMed

Fathollahzadeh, M; Hosseini, M; Haghighi, B; Kolahdouz, M; Fathipour, M

2016-06-14

This study presents fabrication of a liquid-gated enzyme field effect device and its implementation as a glucose biosensor. The device consisted of four electrodes on a glass substrate with a channel functionalized by carboxylated multi-walled carbon nanotubes-polyaniline nanocomposite (MWCNTCOOH/PAn) and glucose oxidase. The resistance of functionalized channel increased with increasing the concentration of glucose when an electric field was applied to the liquid gate. The most effective and stable performance was obtained at the applied electric field of 100 mV. The device resistance, R, exhibited a linear relationship with the logarithm of glucose concentration in the range between 0.005 and 500 mM glucose. The detection limit (S/N = 3) for glucose was about 0.5 μM. Large effective area and good conductivity properties of MWCNTCOOH/PAn nanocomposite were the key features of the fabricated sensitive and stable glucose biosensor. Copyright © 2016 Elsevier B.V. All rights reserved.

A glucose-responsive insulin therapy protects animals against hypoglycemia

PubMed Central

Yang, Ruojing; Wu, Margaret; Lin, Songnian; Nargund, Ravi P.; Li, Xinghai; Kelly, Theresa; Yan, Lin; Dai, Ge; Qian, Ying; Dallas-yang, Qing; Fischer, Paul A.; Cui, Yan; Shen, Xiaolan; Huo, Pei; Feng, Danqing Dennis; Erion, Mark D.; Kelley, David E.

2018-01-01

Hypoglycemia is commonly associated with insulin therapy, limiting both its safety and efficacy. The concept of modifying insulin to render its glucose-responsive release from an injection depot (of an insulin complexed exogenously with a recombinant lectin) was proposed approximately 4 decades ago but has been challenging to achieve. Data presented here demonstrate that mannosylated insulin analogs can undergo an additional route of clearance as result of their interaction with endogenous mannose receptor (MR), and this can occur in a glucose-dependent fashion, with increased binding to MR at low glucose. Yet, these analogs retain capacity for binding to the insulin receptor (IR). When the blood glucose level is elevated, as in individuals with diabetes mellitus, MR binding diminishes due to glucose competition, leading to reduced MR-mediated clearance and increased partitioning for IR binding and consequent glucose lowering. These studies demonstrate that a glucose-dependent locus of insulin clearance and, hence, insulin action can be achieved by targeting MR and IR concurrently. PMID:29321379

Olfactory stimulation modulates the blood glucose level in rats.

PubMed

Tsuji, Tadataka; Tanaka, Susumu; Bakhshishayan, Sanam; Kogo, Mikihiko; Yamamoto, Takashi

2018-01-01

In both humans and animals, chemosensory stimuli, including odors and tastes, induce a variety of physiologic and mental responses related to energy homeostasis, such as glucose kinetics. The present study examined the importance of olfactory function in glucose kinetics following ingestion behavior in a simplified experimental scenario. We applied a conventional glucose tolerance test to rats with and without olfactory function and analyzed subsequent blood glucose (BG) curves in detail. The loss of olfactory input due to experimental damage to the olfactory mucosa induced a marked decrease in the area under the BG curve. Exposure to grapefruit odor and its main component, limonene, both of which activate the sympathetic nerves, before glucose loading also greatly depressed the BG curve. Pre-loading exposure to lavender odor, a parasympathetic activator, stabilized the BG level. These results suggest that olfactory function is important for proper glucose kinetics after glucose intake and that certain fragrances could be utilized as tools for controlling BG levels.

Induction of Fos expression in the rat forebrain after intragastric administration of monosodium L-glutamate, glucose and NaCl.

PubMed

Otsubo, H; Kondoh, T; Shibata, M; Torii, K; Ueta, Y

2011-11-24

l-glutamate, an umami taste substance, is a key molecule coupled to a food intake signaling pathway. Furthermore, recent studies have unveiled new roles for dietary glutamate on gut-brain axis communication via activation of gut glutamate receptors and subsequent vagus nerve. In the present study, we mapped activation sites of the rat forebrain after intragastric load of 60 mM monosodium l-glutamate (MSG) by measurement of Fos protein, a functional marker of neuronal activation. The same concentration of d-glucose (sweet) and NaCl (salty) was used as controls. MSG administration exclusively produced enhanced Fos expression in four hypothalamic regions (the medial preoptic area, lateral hypothalamic area, dorsomedial nucleus, and arcuate nucleus). On the other hand, glucose administration exclusively enhanced Fos induction in the nucleus accumbens. Both MSG and glucose enhanced Fos induction in three brain regions (the habenular nucleus, paraventricular nucleus, and central nucleus of the amygdala). However, MSG induced Fos inductions were more potent than those of glucose in the habenular nucleus and paraventricular nucleus. Importantly, the present study identified for the first time two brain areas (the paraventricular and arcuate hypothalamic nuclei) that are more potently activated by intragastric MSG loads compared with glucose and NaCl. Overall, our results suggest significant activation of a neural network comprising the habenular nucleus, amygdala, and the hypothalamic subnuclei following intragastric load with glutamate. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Detoxification and fermentation of pyrolytic sugar for ethanol production.

PubMed

Wang, Hui; Livingston, Darrell; Srinivasan, Radhakrishnan; Li, Qi; Steele, Philip; Yu, Fei

2012-11-01

The sugars present in bio-oil produced by fast pyrolysis can potentially be fermented by microbial organisms to produce cellulosic ethanol. This study shows the potential for microbial digestion of the aqueous fraction of bio-oil in an enrichment medium to consume glucose and produce ethanol. In addition to glucose, inhibitors such as furans and phenols are present in the bio-oil. A pure glucose enrichment medium of 20 g/l was used as a standard to compare with glucose and aqueous fraction mixtures for digestion. Thirty percent by volume of aqueous fraction in media was the maximum additive amount that could be consumed and converted to ethanol. Inhibitors were removed by extraction, activated carbon, air stripping, and microbial methods. After economic analysis, the cost of ethanol using an inexpensive fermentation medium in a large scale plant is approximately $14 per gallon.

Calpain activation induced by glucose deprivation is mediated by oxidative stress and contributes to neuronal damage.

PubMed

Páramo, Blanca; Montiel, Teresa; Hernández-Espinosa, Diego R; Rivera-Martínez, Marlene; Morán, Julio; Massieu, Lourdes

2013-11-01

The mechanisms leading to neuronal death during glucose deprivation have not been fully elucidated, but a role of oxidative stress has been suggested. In the present study we have investigated whether the production of reactive oxygen species during glucose deprivation, contributes to the activation of calpain, a calcium-dependent protease involved in neuronal injury associated with brain ischemia and cerebral trauma. We have observed a rapid activation of calpain, as monitored by the cleavage of the cytoskeletal protein α-spectrin, after glucose withdrawal, which is reduced by inhibitors of xanthine oxidase, phospholipase A2 and NADPH oxidase. Results suggest that phospholipase A2 and NADPH oxidase contribute to the early activation of calpain after glucose deprivation. In particular NOX2, a member of the NADPH oxidase family is involved, since reduced stimulation of calpain activity is observed after glucose deprivation in hippocampal slices from transgenic mice lacking a functional NOX2. We observed an additive effect of the inhibitors of xanthine oxidase and phospholipase A2 on both ROS production and calpain activity, suggesting a synergistic action of these two enzymes. The present results provide new evidence showing that reactive oxygen species stimulate calpain activation during glucose deprivation and that this mechanism is involved in neuronal death. Copyright © 2013 Elsevier Ltd. All rights reserved.

A ``plasmonic cuvette'': dye chemistry coupled to plasmonic interferometry for glucose sensing

NASA Astrophysics Data System (ADS)

Siu, Vince S.; Feng, Jing; Flanigan, Patrick W.; Palmore, G. Tayhas R.; Pacifici, Domenico

2014-06-01

A non-invasive method for the detection of glucose is sought by millions of diabetic patients to improve personal management of blood glucose over a lifetime. In this work, the synergistic advantage of combining plasmonic interferometry with an enzyme-driven dye assay yields an optical sensor capable of detecting glucose in saliva with high sensitivity and selectivity. The sensor, coined a "plasmonic cuvette," is built around a nano-scale groove-slit-groove (GSG) plasmonic interferometer coupled to an Amplex-red/Glucose-oxidase/Glucose (AR/GOx/Glucose) assay. The proposed device is highly sensitive, with a measured intensity change of 1.7×105%/m (i.e., one order of magnitude more sensitive than without assay) and highly specific for glucose sensing in picoliter volumes, across the physiological range of glucose concentrations found in human saliva (20-240 μm). Real-time glucose monitoring in saliva is achieved by performing a detailed study of the underlying enzyme-driven reactions to determine and tune the effective rate constants in order to reduce the overall assay reaction time to ˜2 min. The results reported suggest that by opportunely choosing the appropriate dye chemistry, a plasmonic cuvette can be turned into a general, real-time sensing scheme for detection of any molecular target, with high sensitivity and selectivity, within extremely low volumes of biological fluid (down to femtoliters). Hereby, we present the results on glucose detection in artificial saliva as a notable and clinically relevant case study.

Stimulus-dependent changes of extracellular glucose in the rat hippocampus determined by in vivo microdialysis.

PubMed

Rex, A; Bert, B; Fink, H; Voigt, J-P

2009-10-19

Neuronal activity is tightly coupled with brain energy metabolism; and glucose is an important energy substrate for neurons. The present in vivo microdialysis study was aimed at investigating changes in extracellular glucose concentrations in the rat ventral hippocampus due to exposure to the elevated plus maze. Determination of basal hippocampal glucose and lactate/pyruvate ratio in male Wistar rats was conducted in the home cage using in vivo microdialysis. Rats were exposed to the elevated plus maze, a rodent model of anxiety-related behaviour, or to unspecific stress induced by white noise (95dB) as a control condition. Basal hippocampal levels of glucose, as determined by zero-net-flux, and the basal lactate/pyruvate ratio were 1.49+/-0.05mmol/l and 13.8+/-1.1, respectively. In rats without manipulation, glucose levels remained constant throughout the experiment (120min). By contrast, exposure to the elevated plus maze led to a temporary decline in hippocampal glucose (-33.2+/-4.4%) which returned to baseline level in the home cage. White noise caused only a non-significant decrease in extracellular glucose level (-9.3+/-3.5%). In all groups, the lactate/pyruvate ratio remained unchanged by the experimental procedures. Our microdialysis study demonstrates that exposure to the elevated plus maze induces a transient decrease in extracellular hippocampal glucose concentration. In contrast, an unspecific stimulus did not change hippocampal glucose. The latter suggests that only specific behavioural stimuli increase hippocampal glucose utilization in the ventral hippocampus.

Toward CMOS image sensor based glucose monitoring.

PubMed

Devadhasan, Jasmine Pramila; Kim, Sanghyo

2012-09-07

Complementary metal oxide semiconductor (CMOS) image sensor is a powerful tool for biosensing applications. In this present study, CMOS image sensor has been exploited for detecting glucose levels by simple photon count variation with high sensitivity. Various concentrations of glucose (100 mg dL(-1) to 1000 mg dL(-1)) were added onto a simple poly-dimethylsiloxane (PDMS) chip and the oxidation of glucose was catalyzed with the aid of an enzymatic reaction. Oxidized glucose produces a brown color with the help of chromogen during enzymatic reaction and the color density varies with the glucose concentration. Photons pass through the PDMS chip with varying color density and hit the sensor surface. Photon count was recognized by CMOS image sensor depending on the color density with respect to the glucose concentration and it was converted into digital form. By correlating the obtained digital results with glucose concentration it is possible to measure a wide range of blood glucose levels with great linearity based on CMOS image sensor and therefore this technique will promote a convenient point-of-care diagnosis.

Measurements of glucose on the skin surface, in stratum corneum and in transcutaneous extracts: implications for physiological sampling.

PubMed

Cunningham, David D; Young, Douglas F

2003-09-01

Obtaining representative physiological samples for glucose analysis remains a challenge especially when developing less invasive glucose monitoring systems for diabetic patients. In the present study the glucose content of the stratum corneum was compared with the amount of glucose obtained by short aqueous extractions from a site on the dorsal wrist, using high pressure liquid chromatography with pulsed amperometric detection. Ten successive aqueous 1-minute extractions of the site yielded a total of 60 ng cm(-2). The total glucose content of the stratum corneum of the site, determined from 30 successive tape-strippings of the site, was 360 ng cm(-2). After tape-stripping, the transcutaneous aqueous extraction rate was 86 +/- 13 ng cm(-2) min(-1), compared with rates of 80-600 ng cm(-2) min(-1) obtained with suction effusion or microdialysis after tape-stripping. Glucose on the surface of the skin and within the stratum corneum should be considered as sources of extraneous glucose contamination during testing of less invasive glucose monitoring devices.

In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARgamma in L6 myotubes.

PubMed

Anandharajan, R; Jaiganesh, S; Shankernarayanan, N P; Viswakarma, R A; Balakrishnan, A

2006-06-01

The purpose of the present study is to investigate the effect of methanolic extracts of Aegles marmelos and Syzygium cumini on a battery of targets glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARgamma) and phosphatidylinositol 3' kinase (PI3 kinase) involved in glucose transport. A. marmelos and S. cumini are anti-diabetic medicinal plants being used in Indian traditional medicine. Different solvent extracts extracted sequentially were analysed for glucose uptake activity at each step and methanol extracts were found to be significantly active at 100ng/ml dose comparable with insulin and rosiglitazone. Elevation of Glut-4, PPARgamma and PI3 kinase by A. marmelos and S. cumini in association with glucose transport supported the up-regulation of glucose uptake. The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport. Current observation concludes that methanolic extracts of A. marmelos and S. cumini activate glucose transport in a PI3 kinase-dependent fashion.

Evaluation of a Standardized Extract from Morus alba against α-Glucosidase Inhibitory Effect and Postprandial Antihyperglycemic in Patients with Impaired Glucose Tolerance: A Randomized Double-Blind Clinical Trial

PubMed Central

Hwang, Seung Hwan; Li, Hong Mei; Wang, Zhiqiang

2016-01-01

To evaluate the antihyperglycemic effect of a standardized extract of the leaves of Morus alba (SEMA), the present study was designed to investigate the α-glucosidase inhibitory effect and acute single oral toxicity as well as evaluate blood glucose reduction in animals and in patients with impaired glucose tolerance in a randomized double-blind clinical trial. SEMA was found to inhibit α-glucosidase at a fourfold higher level than the positive control (acarbose), in a concentration-dependent manner. Moreover, blood glucose concentration was suppressed by SEMA in vivo. Clinical signs and weight changes were observed when conducting an evaluation of the acute toxicity of SEMA through a single-time administration, with clinical observation conducted more than once each day. After administration of the SEMA, observation was for 14 days; all of the animals did not die and did not show any abnormal symptoms. In addition, the inhibitory effects of rice coated with SEMA were evaluated in a group of impaired glucose tolerance patients on postprandial glucose and a group of normal persons, and results showed that SEMA had a clear inhibitory effect on postprandial hyperglycemia in both groups. Overall, SEMA showed excellent potential in the present study as a material for improving postprandial hyperglycemia. PMID:27974904

Suggestion of a Numerical Model for the Blood Glucose Adjustment with Ingesting a Food

NASA Astrophysics Data System (ADS)

Yamamoto, Naokatsu; Takai, Hiroshi

In this study, we present a numerical model of the time dependence of blood glucose value after ingesting a meal. Two numerical models are proposed in this paper to explain a digestion mechanism and an adjustment mechanism of blood glucose in the body, respectively. It is considered that models are exhibited by using simple equations with a transfer function and a block diagram. Additionally, the time dependence of blood glucose was measured, when subjects ingested a sucrose or a starch. As a result, it is clear that the calculated result of models using a computer can be fitted very well to the measured result of the time dependence of blood glucose. Therefore, it is considered that the digestion model and the adjustment model are useful models in order to estimate a blood glucose value after ingesting meals.

Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPAR gamma and PI3K.

PubMed

Kumar, Ramadhar; Balaji, S; Uma, T S; Sehgal, P K

2009-12-10

Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor. The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPAR gamma) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent. Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-D-[1-(3)H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPAR gamma and PI3K have been studied. The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 microg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPAR gamma and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake. This study demonstrated the significance of Glut-4, PPAR gamma and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.

[Cardiac risk profile in diabetes mellitus and impaired fasting glucose].

PubMed

Schaan, Beatriz D'Agord; Harzheim, Erno; Gus, Iseu

2004-08-01

Mortality of diabetic patients is higher than that of the population at large, and mainly results from cardiovascular diseases. The purpose of the present study was to identify the prevalence of cardiovascular risk factors in subjects with diabetes mellitus (DM) or abnormal fasting glucose (FG) in order to guide health actions. A population-based cross-sectional study was carried out in a representative random cluster sampling of 1,066 adult urban population (> or =20 years) in the state of Rio Grande do Sul between 1999 and 2000. A structured questionnaire on coronary risk factors was applied and sociodemographic characteristics of all adults older than 20 years living in the same dwelling were collected. Subjects were clinically evaluated and blood samples were obtained for measuring total cholesterol and fasting glycemia. Statistical analysis was performed using Stata 7 and a 5% significance level was set. Categorical variables were compared by Pearson's chi-square and continuous variables were compared using Student's t-test or Anova and multivariate analysis, all controlled for the cluster effect. Of 992 subjects, 12.4% were diabetic and 7.4% had impaired fasting glucose. Among the risk factors evaluated, subjects who presented any kind of glucose homeostasis abnormality were at a higher prevalence of obesity (17.8, 29.2 and 35.3% in healthy subjects, impaired fasting glucose and DM respectively, p<0.001), hypertension (30.1, 56.3 and 50.5% in healthy subjects, impaired fasting glucose and DM, respectively, p<0.001), and hypercholesterolemia (23.2, 35.1 and 39.5 in healthy subjects, impaired fasting glucose and DM respectively, p=0.01). Subjects with any kind of glucose homeostasis abnormality represent a group, which preventive individual and population health policies should target since they have higher prevalence of coronary artery disease risk factors.

Reduction of fumonisin B₁ in corn grits by twin-screw extrusion.

PubMed

Jackson, Lauren S; Jablonski, Joseph; Bullerman, Lloyd B; Bianchini, Andreia; Hanna, Milford A; Voss, Kenneth A; Hollub, April D; Ryu, Dojin

2011-08-01

This study was designed to investigate the fate of fumonisins in flaking corn grits during twin-screw extrusion by measuring fumonisin B₁ (FB₁) and its analogs with a mass balance approach. Food grade corn grits and 2 batches of grits contaminated with FB₁ at 10 and 50 μg/g by Fusarium verticillioides M-2552 were processed with or without glucose supplementation (10%, w/w) with a twin-screw extruder. Extrusion reduced FB₁ in contaminated grits by 64% to 72% without glucose and 89% to 94% with added glucose. In addition, extrusion alone resulted in 26% to 73% reduction in the levels of fumonisin B₂ and fumonisin B₃, while levels of both mycotoxins were reduced by >89% in extruded corn grits containing 10% glucose. Mass balance analysis showed that 38% to 46% of the FB₁ species detected in corn extruded with glucose was N-(deoxy-D-fructos-1-yl)-FB₁, while 23% to 37% of FB₁ species detected in extruded corn grits with and without added glucose was bound to the matrix. It was also found that the hydrolyzed form of FB₁ was a minor species in extruded corn grits with or without added glucose, representing <15% of the total FB₁ species present. Less than 46% of FB₁ originally present in corn grits could be detected in the fumonisin analogues measured in this study. Research is needed to identify the reaction products resulting from extrusion processing of fumonisin-contaminated corn products. Twin-screw extrusion is widely used in food industry for its versatility. This technology may reduce the level of fumonisins in corn particularly with added glucose. Journal of Food Science © 2011 Institute of Food Technologists® No claim to original US government works.

Reforming and decomposition of glucose in an aqueous phase

NASA Technical Reports Server (NTRS)

Amin, S.; Reid, R. C.; Modell, M.

1975-01-01

Exploratory experiments have been carried out to study the decomposition of glucose, a typical carbohydrate, in a high temperature-high pressure water reactor. The objective of the study was to examine the feasibility of such a process to decompose cellulosic waste materials in long-term space missions. At temperatures below the critical point of water, glucose decomposed to form liquid products and char. Little gas was noted with or without reforming catalysts present. The rate of the primary glucose reaction increased significantly with temperature. Partial identification of the liquid phase was made and the C:H:O ratios determined for both the liquid and solid products. One of the more interesting results from this study was the finding that when glucose was injected into a reactor held at the critical temperature (and pressure) of water, no solid products formed. Gas production increased, but the majority of the carbon was found in soluble furans (and furan derivatives). This significant result is now being investigated further.

Effect of cholera toxin administered supraspinally or spinally on the blood glucose level in pain and d-glucose fed animal models.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Choi, Seong-Soo; Suh, Hong-Won

2013-04-01

In the present study, the effect of intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration with cholera toxin (CTX) on the blood glucose level was examined in ICR mice. The i.t. treatment with CTX alone for 24 h dose-dependently increased the blood glucose level. However, i.c.v. treatment with CTX for 24 h did not affect the blood glucose level. When mice were orally fed with D-glucose (2 g/kg), the blood glucose level reached to a maximum level at 30 min and almost returned to the control level at 120 min after D-glucose feeding. I.c.v. pretreatment with CTX increased the blood glucose level in a potentiative manner, whereas i.t. pretreatment with CTX increased the blood glucose level in an additive manner in a D-glucose fed group. In addition, the blood glucose level was increased in formalin-induced pain animal model. I.c.v. pretreatment with CTX enhanced the blood glucose level in a potentiative manner in formalin-induced pain animal model. On the other hand, i.t. pretreatment with CTX increased the blood glucose level in an additive manner in formalin-induced pain animal model. Our results suggest that CTX administered supraspinally or spinally differentially modulates the regulation of the blood glucose level in D-glucose fed model as well as in formalin-induced pain model.

Twenty-four-hour variations in blood glucose level in Japanese type 2 diabetes patients based on continuous glucose monitoring.

PubMed

Hajime, Maiko; Okada, Yosuke; Mori, Hiroko; Otsuka, Takashi; Kawaguchi, Mayuko; Miyazaki, Megumi; Kuno, Fumi; Sugai, Kei; Sonoda, Satomi; Tanaka, Kenichi; Kurozumi, Akira; Narisawa, Manabu; Torimoto, Keiichi; Arao, Tadashi; Tanaka, Yoshiya

2018-01-01

High fluctuations in blood glucose are associated with various complications. The correlation between glycated hemoglobin (HbA1c) level and fluctuations in blood glucose level has not been studied in Japanese patients with type 2 diabetes. In the present study, blood glucose profile stratified by HbA1c level was evaluated by continuous glucose monitoring (CGM) in Japanese type 2 diabetes patients. Our retrospective study included 294 patients with type 2 diabetes who were divided by HbA1c level into five groups (≥6.0 to <7.0%, ≥7.0 to <8.0%, ≥8.0 to <9.0%, ≥9.0 to <10.0% and ≥10%). The correlation between HbA1c level and CGM data was analyzed. The primary end-point was the difference in blood glucose fluctuations among the HbA1c groups. The mean blood glucose level increased significantly with increasing HbA1c (P trend  < 0.01). The standard deviation increased with increases in HbA1c (P trend  < 0.01). The mean amplitude of glycemic excursions did not vary significantly with HbA1c. The levels of maximum blood glucose, minimum blood glucose, each preprandial blood glucose, each postprandial maximum blood glucose, range of increase in postprandial glucose from pre-meal to after breakfast, the area under the blood concentration-time curve >180 mg/dL and percentage of the area under the blood concentration-time curve >180 mg/dL were higher with higher HbA1c. Mean glucose level and pre-breakfast blood glucose level were significant and independent determinants of HbA1c. In Japanese patients treated for type 2 diabetes, the mean amplitude of glycemic excursions did not correlate with HbA1c, making it difficult to assess blood glucose fluctuations using HbA1c. Parameters other than HbA1c are required to evaluate fluctuations in blood glucose level in patients receiving treatment for type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Low cortisol levels in blood from dairy cows with ketosis: a field study

PubMed Central

2010-01-01

Background An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Methods Cortisol, insulin, β-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. Results No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). Conclusions The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research. PMID:20487518

Low cortisol levels in blood from dairy cows with ketosis: a field study.

PubMed

Forslund, Kristina B; Ljungvall, Orjan A; Jones, Bernt V

2010-05-20

An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Cortisol, insulin, beta-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research.

New Insights into Cytosolic Glucose Levels during Differentiation of 3T3-L1 Fibroblasts into Adipocytes*

PubMed Central

Kovacic, Petra Brina; Chowdhury, Helena H.; Velebit, Jelena; Kreft, Marko; Jensen, Jørgen; Zorec, Robert

2011-01-01

Cytosolic glucose concentration reflects the balance between glucose entry across the plasma membrane and cytosolic glucose utilization. In adipocytes, glucose utilization is considered very rapid, meaning that every glucose molecule entering the cytoplasm is quickly phosphorylated. Thus, the cytosolic free glucose concentration is considered to be negligible; however, it was never measured directly. In the present study, we monitored cytosolic glucose dynamics in 3T3-L1 fibroblasts and adipocytes by expressing a fluorescence resonance energy transfer (FRET)-based glucose nanosensor: fluorescent indicator protein FLIPglu-600μ. Specifically, we monitored cytosolic glucose responses by varying transmembrane glucose concentration gradient. The changes in cytosolic glucose concentration were detected in only 56% of 3T3-L1 fibroblasts and in 14% of 3T3-L1 adipocytes. In adipocytes, the resting cytosolic glucose concentration was reduced in comparison with the one recorded in fibroblasts. Membrane permeabilization increased cytosolic glucose concentration in adipocytes, and glycolytic inhibitor iodoacetate failed to increase cytosolic glucose concentration, indicating low adipocyte permeability for glucose at rest. We also examined the effects of insulin and adrenaline. Insulin significantly increased cytosolic glucose concentration in adipocytes by a factor of 3.6; however, we recorded no effect on delta ratio (ΔR) in fibroblasts. Adrenaline increased cytosolic glucose concentration in fibroblasts but not in adipocytes. However, in adipocytes in insulin-stimulated conditions, glucose clearance was significantly faster following adrenaline addition in comparison with controls (p < 0.001). Together, these results demonstrate that during differentiation, adipocytes develop more efficient mechanisms for maintaining low cytosolic glucose concentration, predominantly with reduced membrane permeability for glucose. PMID:21349852

Glucose transport in brain - effect of inflammation.

PubMed

Jurcovicova, J

2014-01-01

Glucose is transported across the cell membrane by specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient. In the brain, both types of transporters are present with different function, affinity, capacity, and tissue distribution. GLUT1 occurs in brain in two isoforms. The more glycosylated GLUT1 is produced in brain microvasculature and ensures glucose transport across the blood brain barrier (BBB). The less glycosylated form is localized in astrocytic end-feet and cell bodies and is not present in axons, neuronal synapses or microglia. Glucose transported to astrocytes by GLUT1 is metabolized to lactate serving to neurons as energy source. Proinflammatory cytokine interleukin (IL)-1β upregulates GLUT1 in endothelial cells and astrocytes, whereas it induces neuronal death in neuronal cell culture. GLUT2 is present in hypothalamic neurons and serves as a glucose sensor in regulation of food intake. In neurons of the hippocampus, GLUT2 is supposed to regulate synaptic activity and neurotransmitter release. GLUT3 is the most abundant glucose transporter in the brain having five times higher transport capacity than GLUT1. It is present in neuropil, mostly in axons and dendrites. Its density and distribution correlate well with the local cerebral glucose demands. GLUT5 is predominantly fructose transporter. In brain, GLUT5 is the only hexose transporter in microglia, whose regulation is not yet clear. It is not present in neurons. GLUT4 and GLUT8 are insulin-regulated glucose transporters in neuronal cell bodies in the cortex and cerebellum, but mainly in the hippocampus and amygdala, where they maintain hippocampus-dependent cognitive functions. Insulin translocates GLUT4 from cytosol to plasma membrane to transport glucose into cells, and GLUT8 from cytosol to rough endoplasmic reticulum to recover redundant glucose to cytosol after protein glycosylation. In autoimmune diseases, the enhanced glucose uptake was found in inflamed peripheral tissue, mainly due to proliferating fibroblasts and activated macrophages. In our experimental model of rheumatoid arthritis (adjuvant arthritis), enhanced 2-deoxy-2[F-18]fluoro-D-glucose was found in the hippocampus and amygdala two days after the induction of the disease which, similarly as in the peripheral joints, can be ascribed to the activated macrophages. The knowledge on the glucose transport and the role of glucose transporters in the brain during systemic autoimmune inflammation is still incomplete and needs further investigations.

Blood glucose monitoring skills in children with Type I diabetes.

PubMed

Perwien, A R; Johnson, S B; Dymtrow, D; Silverstein, J

2000-06-01

While blood glucose monitoring has become increasingly important in diabetes care, studies have yet to address the accuracy of youngsters' performance of blood glucose testing with current reflectance meters. The present study examined testing skills and predictors of accurate testing skills in a sample of 7-14-year-old children attending a summer camp for youth with diabetes (n=266). A 15-item behavior observational skill test was used to assess accuracy of blood glucose monitoring skills with reflectance meters. Accurate performance of individual skills ranged between 14.6% and 99.6% for the sample. However, a number of children made critical errors (errors that were likely to lead to inaccurate blood glucose testing results). When duration of diabetes and metabolic control were controlled, female gender, older age, experience with a particular meter, and absence of hypoglycemia at the time of testing were positively associated with accurate skill performance. Findings suggest that younger children, children using a new blood glucose testing meter, and children suspected of having hypoglycemia should be supervised and observed when testing. Although all young children should be supervised when blood glucose testing, boys may need closer supervision until an older age than girls. This study underscores the need for health care providers to periodically observe children's blood glucose monitoring techniques to assure accurate testing habits and to correct problematic testing behaviors.

Correlation between high blood IL-6 level, hyperglycemia, and glucose control in septic patients.

PubMed

Nakamura, Masataka; Oda, Shigeto; Sadahiro, Tomohito; Watanabe, Eizo; Abe, Ryuzo; Nakada, Taka-Aki; Morita, Yasumasa; Hirasawa, Hiroyuki

2012-12-12

The aim of the present study was to investigate the relationship between the blood IL-6 level, the blood glucose level, and glucose control in septic patients. This retrospective observational study in a general ICU of a university hospital included a total of 153 patients with sepsis, severe sepsis, or septic shock who were admitted to the ICU between 2005 and 2010, stayed in the ICU for 7 days or longer, and did not receive steroid therapy prior to or after ICU admission. The severity of stress hyperglycemia, status of glucose control, and correlation between those two factors in these patients were investigated using the blood IL-6 level as an index of hypercytokinemia. A significant positive correlation between blood IL-6 level and blood glucose level on ICU admission was observed in the overall study population (n = 153; r = 0.24, P = 0.01), and was stronger in the nondiabetic subgroup (n = 112; r = 0.42, P < 0.01). The rate of successful glucose control (blood glucose level < 150 mg/dl maintained for 6 days or longer) decreased with increase in blood IL-6 level on ICU admission (P < 0.01). The blood IL-6 level after ICU admission remained significantly higher and the 60-day survival rate was significantly lower in the failed glucose control group than in the successful glucose control group (P < 0.01 and P < 0.01, respectively). High blood IL-6 level was correlated with hyperglycemia and with difficulties in glucose control in septic patients. These results suggest the possibility that hypercytokinemia might be involved in the development of hyperglycemia in sepsis, and thereby might affect the success of glucose control.

Glucose supplement reverses the fasting-induced suppression of cellular immunity in Mongolian gerbils (Meriones unguiculatus).

PubMed

Xu, De-Li; Wang, De-Hua

2011-10-01

Glucose plays an important role in immunity. Three day fasting will decrease cellular immunity and blood glucose levels in Mongolian gerbils (Meriones unguiculatus). In the present study, we tested the hypothesis that glucose supplement can reverse the fasting-induced suppression in cellular immunity in gerbils. Twenty-eight male gerbils were selected and randomly divided into fed and fasting groups. Half of the gerbils in each group were then provided with either 10% glucose water or pure water. After 66 h, each gerbil was injected with phytohaemagglutinin (PHA) solution to challenge cellular immunity. Results showed that glucose supplement restored blood glucose levels in fasted gerbils to those of the fed controls. It also recovered cellular immunity, body fat mass and serum leptin levels in fasted gerbils to the values of the fed controls. Blood glucose levels were positively correlated with body fat mass, leptin levels and cellular immune responses. Thymus and spleen masses, and white blood cells in fasted gerbils were not affected by glucose supplement. In general, our data demonstrate that glucose supplement could reverse fasting-induced suppression of cellular immunity in Mongolian gerbils. Copyright © 2011 Elsevier GmbH. All rights reserved.

Key Enzymes of the Semiphosphorylative Entner-Doudoroff Pathway in the Haloarchaeon Haloferax volcanii: Characterization of Glucose Dehydrogenase, Gluconate Dehydratase, and 2-Keto-3-Deoxy-6-Phosphogluconate Aldolase.

PubMed

Sutter, Jan-Moritz; Tästensen, Julia-Beate; Johnsen, Ulrike; Soppa, Jörg; Schönheit, Peter

2016-08-15

The halophilic archaeon Haloferax volcanii has been proposed to degrade glucose via the semiphosphorylative Entner-Doudoroff (spED) pathway. So far, the key enzymes of this pathway, glucose dehydrogenase (GDH), gluconate dehydratase (GAD), and 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase (KDPGA), have not been characterized, and their functional involvement in glucose degradation has not been demonstrated. Here we report that the genes HVO_1083 and HVO_0950 encode GDH and KDPGA, respectively. The recombinant enzymes show high specificity for glucose and KDPG and did not convert the corresponding C4 epimers galactose and 2-keto-3-deoxy-6-phosphogalactonate at significant rates. Growth studies of knockout mutants indicate the functional involvement of both GDH and KDPGA in glucose degradation. GAD was purified from H. volcanii, and the encoding gene, gad, was identified as HVO_1488. GAD catalyzed the specific dehydration of gluconate and did not utilize galactonate at significant rates. A knockout mutant of GAD lost the ability to grow on glucose, indicating the essential involvement of GAD in glucose degradation. However, following a prolonged incubation period, growth of the Δgad mutant on glucose was recovered. Evidence is presented that under these conditions, GAD was functionally replaced by xylonate dehydratase (XAD), which uses both xylonate and gluconate as substrates. Together, the characterization of key enzymes and analyses of the respective knockout mutants present conclusive evidence for the in vivo operation of the spED pathway for glucose degradation in H. volcanii The work presented here describes the identification and characterization of the key enzymes glucose dehydrogenase, gluconate dehydratase, and 2-keto-3-deoxy-6-phosphogluconate aldolase and their encoding genes of the proposed semiphosphorylative Entner-Doudoroff pathway in the haloarchaeon Haloferax volcanii The functional involvement of the three enzymes was proven by analyses of the corresponding knockout mutants. These results provide evidence for the in vivo operation of the semiphosphorylative Entner-Doudoroff pathway in haloarchaea and thus expand our understanding of the unusual sugar degradation pathways in the domain Archaea. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

PubMed

Prodam, F; Gasco, V; Caputo, M; Zavattaro, M; Pagano, L; Marzullo, P; Belcastro, S; Busti, A; Perino, C; Grottoli, S; Ghigo, E; Aimaretti, G

2013-08-01

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients. We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Subjects with impaired fasting glucose: evolution in a period of 6 years.

PubMed

Leiva, E; Mujica, V; Orrego, R; Wehinger, S; Soto, A; Icaza, G; Vásquez, M; Díaz, L; Andrews, M; Arredondo, M

2014-01-01

To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients.

High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5

PubMed Central

Wang, Juan; Shibayama, Yuki; Kobori, Hiroyuki; Liu, Ya; Kobara, Hideki; Masaki, Tsutomu; Wang, Zhiyu

2017-01-01

High glucose has been demonstrated to induce angiotensinogen (AGT) synthesis in the renal proximal tubular cells (RPTCs) of rats, which may further activate the intrarenal renin-angiotensin system (RAS) and contribute to diabetic nephropathy. This study aimed to investigate the effects of high glucose on AGT in the RPTCs of human origin and identify the glucose-responsive transcriptional factor(s) that bind(s) to the DNA sequences of AGT promoter in human RPTCs. Human kidney (HK)-2 cells were treated with normal glucose (5.5 mM) and high glucose (15.0 mM), respectively. Levels of AGT mRNA and AGT secretion of HK-2 cells were measured by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Consecutive 5’-end deletion mutant constructs and different site-directed mutagenesis products of human AGT promoter sequences were respectively transfected into HK-2 cells, followed by AGT promoter activity measurement through dual luciferase assay. High glucose significantly augmented the levels of AGT mRNA and AGT secretion of HK-2 cells, compared with normal glucose treatment. High glucose also significantly augmented AGT promoter activity in HK-2 cells transfected with the constructs of human AGT promoter sequences, compared with normal glucose treatment. Hepatocyte nuclear factor (HNF)-5 was found to be one of the glucose-responsive transcriptional factors of AGT in human RPTCs, since the mutation of its binding sites within AGT promoter sequences abolished the above effects of high glucose on AGT promoter activity as well as levels of AGT mRNA and its secretion. The present study has demonstrated, for the first time, that high glucose augments AGT in human RPTCs through HNF-5, which provides a potential therapeutic target for diabetic nephropathy. PMID:29053707

Glucose repression may involve processes with different sugar kinase requirements.

PubMed Central

Sanz, P; Nieto, A; Prieto, J A

1996-01-01

Adding glucose to Saccharomyces cerevisiae cells growing among nonfermentable carbon sources leads to glucose repression. This process may be resolved into several steps. An early repression response requires any one of the three glucose kinases present in S. cerevisiae (HXK1, HXK2, or GLK1). A late response is only achieved when Hxk2p is present. PMID:8755906

Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

PubMed

Romain, A J; Letendre, E; Akrass, Z; Avignon, A; Karelis, A D; Sultan, A; Abdel-Baki, A

2017-04-01

Aim: Prediabetes and type 2 diabetes are highly prevalent among individuals with serious mental illness and increased by antipsychotic medication. Although widely recommended, many obstacles prevent these patients from obtaining a proper screening for dysglycemia. Currently, glycated hemoglobin (HbA1c), fasting glucose, and 2-hour glucose levels from the oral glucose tolerance test are used for screening prediabetes and type 2 diabetes. The objective of this study was to investigate if HbA1c could be used as the only screening test among individuals with serious mental illness. Methods: Cross sectional study comparing the sensitivity of HbA1c, fasting glucose, and 2-h oral glucose tolerance test to detect dysglycemias in serious mental illness participants referred for metabolic complications. Results: A total of 84 participants (43 female; aged: 38.5±12.8 years; BMI: 35.0±6.8 kg/m²) was included. Regarding prediabetes, 44, 44 and 76% were identified by HbA1c, fasting glucose, and 2 h- oral glucose tolerance test respectively and for type 2 diabetes, 60, 53 and 66% were identified by HbA1c, fasting glucose and 2 h-oral glucose tolerance test. The overlap between the 3 markers was low (8% of participants for prediabetes and 26% for Type 2 diabetes). Sensitivity of HbA1c were moderate (range 40-62.5%), while its specificity was excellent (92-93%). Conclusion: The present study indicates a low agreement between HbA1c, fasting glucose and 2-h oral glucose tolerance test. It appears that these markers do not identify the same participants. Thus, HbA1c may not be used alone to detect all glucose abnormalities among individuals with serious mental illness. © Georg Thieme Verlag KG Stuttgart · New York.

Does a reduced glucose intake prevent hyperglycemia in children early after cardiac surgery? a randomized controlled crossover study

PubMed Central

2012-01-01

Introduction Hyperglycemia in children after cardiac surgery can be treated with intensive insulin therapy, but hypoglycemia is a potential serious side effect. The aim of this study was to investigate the effects of reducing glucose intake below standard intakes to prevent hyperglycemia, on blood glucose concentrations, glucose kinetics and protein catabolism in children after cardiac surgery with cardiopulmonary bypass (CPB). Methods Subjects received a 4-hour low glucose (LG; 2.5 mg/kg per minute) and a 4-hour standard glucose (SG; 5.0 mg/kg per minute) infusion in a randomized blinded crossover setting. Simultaneously, an 8-hour stable isotope tracer protocol was conducted to determine glucose and leucine kinetics. Data are presented as mean ± SD or median (IQR); comparison was made by paired samples t test. Results Eleven subjects (age 5.1 (20.2) months) were studied 9.5 ± 1.9 hours post-cardiac surgery. Blood glucose concentrations were lower during LG than SG (LG 7.3 ± 0.7 vs. SG 9.3 ± 1.8 mmol/L; P < 0.01), although the glycemic target (4.0-6.0 mmol/L) was not achieved. No hypoglycemic events occurred. Endogenous glucose production was higher during LG than SG (LG 2.9 ± 0.8 vs. SG 1.5 ± 1.1 mg/kg per minute; P = 0.02), due to increased glycogenolysis (LG 1.0 ± 0.6 vs. SG 0.0 ± 1.0 mg/kg per minute; P < 0.05). Leucine balance, indicating protein balance, was negative but not affected by glucose intake (LG -54.8 ± 14.6 vs. SG -58.8 ± 16.7 μmol/kg per hour; P = 0.57). Conclusions Currently recommended glucose intakes aggravated hyperglycemia in children early after cardiac surgery with CPB. Reduced glucose intake decreased blood glucose concentrations without causing hypoglycemia or affecting protein catabolism, but increased glycogenolysis. Trial registration Dutch trial register NTR2079. PMID:23031354

The effect of glutathione S-transferase M1 and T1 polymorphisms on blood pressure, blood glucose, and lipid profiles following the supplementation of kale (Brassica oleracea acephala) juice in South Korean subclinical hypertensive patients

PubMed Central

Han, Jeong-Hwa; Lee, Hye-Jin; Kim, Tae-Seok

2015-01-01

BACKGROUND/OBJECTIVES Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. This study examines whether daily supplementation of kale juice can modulate blood pressure (BP), levels of lipid profiles, and blood glucose, and whether this modulation could be affected by the GSTM1 and GSTT1 polymorphisms. SUBJECTS/METHODS 84 subclinical hypertensive patients showing systolic BP over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were collected on 0-week and 6-week in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol) and blood glucose. RESULTS Systolic and diastolic blood pressure was significantly decreased in all patients regardless of their GSTM1 or GSTT1 polymorphisms after kale juice supplementation. Blood glucose level was decreased only in the GSTM1-present genotype, and plasma lipid profiles showed no difference in both the GSTM1-null and GSTM1-present genotypes. In the case of GSTT1, on the other hand, plasma HDL-C was increased and LDL-C was decreased only in the GSTT1-present type, while blood glucose was decreased only in the GSTT1-null genotype. CONCLUSIONS These findings suggest that the supplementation of kale juice affected blood pressure, lipid profiles, and blood glucose in subclinical hypertensive patients depending on their GST genetic polymorphisms, and the improvement of lipid profiles was mainly greater in the GSTT1-present genotype and the decrease of blood glucose was greater in the GSTM1-present or GSTT1-null genotypes. PMID:25671068

Genetic disruption of SOD1 gene causes glucose intolerance and impairs β-cell function.

PubMed

Muscogiuri, Giovanna; Salmon, Adam B; Aguayo-Mazzucato, Cristina; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Giaccari, Andrea; Reddick, Robert L; Reyna, Sara M; Weir, Gordon; Defronzo, Ralph A; Van Remmen, Holly; Musi, Nicolas

2013-12-01

Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction.

Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function

PubMed Central

Muscogiuri, Giovanna; Salmon, Adam B.; Aguayo-Mazzucato, Cristina; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Giaccari, Andrea; Reddick, Robert L.; Reyna, Sara M.; Weir, Gordon; DeFronzo, Ralph A.; Van Remmen, Holly; Musi, Nicolas

2013-01-01

Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow–fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction. PMID:24009256

Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of age: a 13C NMR metabolomic study.

PubMed

Zhou, Qi; Zheng, Hong; Chen, Jiuxia; Li, Chen; Du, Yao; Xia, Huanhuan; Gao, Hongchang

2018-06-26

Alzheimer's disease (AD) has been associated with the disturbance of brain glucose metabolism. The present study investigates brain glucose metabolism using 13 C NMR metabolomics in combination with intravenous [1- 13 C]-glucose infusion in APP/PS1 transgenic mouse model of amyloid pathology at 10 months of age. We found that brain glucose was significantly accumulated in APP/PS1 mice relative to wild-type (WT) mice. Reductions in 13 C fluxes into the specific carbon sites of tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters (glutamate, glutamine, γ-aminobutyric acid and aspartate) from [1- 13 C]-glucose were also detected in the brain of APP/PS1 mice. In addition, our results reveal that the 13 C-enrichments of the C3 of alanine were significantly lower and the C3 of lactate have a tendency to be lower in the brain of APP/PS1 mice than WT mice. Taken together, the development of amyloid pathology could cause a reduction in glucose utilization and further result in decreases in energy and neurotransmitter metabolism as well as the lactate-alanine shuttle in the brain.

Characterization of mammalian glucose transport proteins using photoaffinity labeling techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wadzinski, B.E.

1989-01-01

A carrier-free radioiodinated phenylazide derivative of forskolin, 3-iodo-4-azidophenethylamido-7-O-succinyl-deacetyl-forskolin (({sup 125}I)IAPS-forskolin), has been shown to be a highly selective photoaffinity probe for the human erythrocyte glucose transported and the glucose transport proteins found in several mammalian tissues and cultured cells where the glucose transport protein is present at a low concentration. The photoincorporation of ({sup 125}I)IAPS-forskolin into these glucose transporters was blocked by D- (but not L-) glucose, cytochalasin B, and forskolin. In addition to labeling the mammalian glucose transport proteins, ({sup 125}I)IAPS-forskolin also labeled the L-arabinose transporter from E. coli. In muscle and adipose tissues, glucose transport is markedly increasedmore » in response to insulin. ({sup 125}I)IAPS-forskolin was shown to selectivity tag the glucose transporter in membranes derived from these cells. In addition, the covalent derivatization of the transport protein in subcellular fractions of the adipocyte has provided a means to study the hormonal regulation of glucose transport. ({sup 125}I)IAPS-forskolin has also been used to label the purified human erythrocyte glucose transporter. The site of insertion has therefore been localized by analysis of the radiolabeled peptides which were produced following chemical and proteolytic digestion of the labeled transport protein.« less

Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

PubMed Central

Wu, Hui; Xu, Xiao; Meng, Ying; Xia, Fangzhen; Zhai, Hualing; Lu, Yingli

2014-01-01

Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1) was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo. PMID:24772449

Influence of abdominal surgical trauma and intra-operative infusion of glucose on splanchnic glucose metabolism in man.

PubMed

Stjernström, H; Jorfeldt, L; Wiklund, L

1981-10-01

Abdominal surgery increases blood glucose concentration and peripheral release and splanchnic uptake of gluconeogenic substrates, including alanine. During trauma or sepsis, infusion of glucose fails to depress alanine conversion to glucose. The effect of intra-operative glucose infusion on splanchnic metabolism was examined in the present study. In eight patients undergoing elective cholecystectomy, splanchnic glucose metabolism was investigated before, during and immediately after surgery. Glucose was infused at a constant rate of 1 mmol/min. Splanchnic blood flow and arterio-hepatic venous differences of oxygen, glucose, lactate, glycerol, 3-hydroxybutyrate and alanine were measured. Eight other patients, who received saline instead of glucose, served as a control group. Infusion of glucose resulted in total inhibition of splanchnic glucose release before as well as during and immediately after surgery. This was observed, even before surgery, at an arterial glucose level which was lower than that in the control group at the end of and immediately after surgery, at which no decrease of the splanchnic glucose release was recorded. changes in neuronal and hormonal factors due to the surgical trauma are considered responsible for this difference in glucose homeostasis. Splanchnic alanine uptake increased during surgery in both groups, but tended to be somewhat lower in the glucose group. The arterial glycerol concentration and splanchnic uptake, as well as the arterial concentration and splanchnic release of 3-hydroxybutyrate, were reduced. It is concluded that an intravenous infusion of glucose at the rate of 1 mmol/min during abdominal surgery (a) increases the arterial blood glucose level and abolishes splanchnic glucose release, (b) reduces, but does not totally prevent the increase in splanchnic uptake of gluconeogenic substrates, and (c) diminishes lipolysis and the formation of 3-hydroxybutyrate.

Achieving the same for less: improving mood depletes blood glucose for people with poor (but not good) emotion control.

PubMed

Niven, Karen; Totterdell, Peter; Miles, Eleanor; Webb, Thomas L; Sheeran, Paschal

2013-01-01

Previous studies have found that acts of self-control like emotion regulation deplete blood glucose levels. The present experiment investigated the hypothesis that the extent to which people's blood glucose levels decline during emotion regulation attempts is influenced by whether they believe themselves to be good or poor at emotion control. We found that although good and poor emotion regulators were equally able to achieve positive and negative moods, the blood glucose of poor emotion regulators was reduced after performing an affect-improving task, whereas the blood glucose of good emotion regulators remained unchanged. As evidence suggests that glucose is a limited energy resource upon which self-control relies, the implication is that good emotion regulators are able to achieve the same positive mood with less cost to their self-regulatory resource. Thus, depletion may not be an inevitable consequence of engaging in emotion regulation.

Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans.

PubMed

List, James F; Whaley, Jean M

2011-03-01

Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve β-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing.

CMOS image sensors as an efficient platform for glucose monitoring.

PubMed

Devadhasan, Jasmine Pramila; Kim, Sanghyo; Choi, Cheol Soo

2013-10-07

Complementary metal oxide semiconductor (CMOS) image sensors have been used previously in the analysis of biological samples. In the present study, a CMOS image sensor was used to monitor the concentration of oxidized mouse plasma glucose (86-322 mg dL(-1)) based on photon count variation. Measurement of the concentration of oxidized glucose was dependent on changes in color intensity; color intensity increased with increasing glucose concentration. The high color density of glucose highly prevented photons from passing through the polydimethylsiloxane (PDMS) chip, which suggests that the photon count was altered by color intensity. Photons were detected by a photodiode in the CMOS image sensor and converted to digital numbers by an analog to digital converter (ADC). Additionally, UV-spectral analysis and time-dependent photon analysis proved the efficiency of the detection system. This simple, effective, and consistent method for glucose measurement shows that CMOS image sensors are efficient devices for monitoring glucose in point-of-care applications.

Influence of HbA1c levels on platelet function profiles associated with tight glycemic control in patients presenting with hyperglycemia and an acute coronary syndrome. A subanalysis of the CHIPS Study ("Control de HIperglucemia y Actividad Plaquetaria en Pacientes con Síndrome Coronario Agudo").

PubMed

Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle-Pascual, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

2013-02-01

Patients with hyperglycemia, an acute coronary syndrome and poor glycemic control have increased platelet reactivity and poor prognosis. However, it is unclear the influence of a tight glycemic control on platelet reactivity in these patients. This is a subanalysis of the CHIPS study. This trial randomized patients with hyperglycemia to undergo an intensive glucose control (target blood glucose 80-120 mg/dL), or conventional glucose control (target blood glucose <180 mg/dL). We analyzed platelet function at discharge on the subgroup of patients with poor glycemic control, defined with admission levels of HbA1c higher than 6.5%. The primary endpoint was maximal platelet aggregation following stimuli with 20 μM ADP. We also measured aggregation following collagen, epinephrine, and thrombin receptor-activated peptide, as well as P2Y12 reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin. A total of 67 patients presented HbA1c ≥ 6.5% (37 intensive, 30 conventional), while 42 had HbA1c < 6.5% (20 intensive, 22 conventional). There were no differences in baseline characteristics between groups. At discharge, patients with HbA1c ≥6.5% had significantly reduced MPA with intensive glucose control compared with conventional control (46.1 ± 22.3 vs. 60.4 ± 20.0%; p = 0.004). Similar findings were shown with other measures of platelet function. However, glucose control strategy did not affect platelet function parameters in patients with HbA1c < 6.5%. Intensive glucose control in patients presenting with an acute coronary syndrome and hyperglycemia results in a reduction of platelet reactivity only in the presence of elevated HbA1c levels.

Protective effect of insulin and glucose at different concentrations on penicillin-induced astrocyte death on the primer astroglial cell line☆

PubMed Central

Özdemir, Mehmet Bülent; Akça, Hakan; Erdoğan, Çağdaş; Tokgün, Onur; Demiray, Aydın; Semin, Fenkçi; Becerir, Cem

2012-01-01

Astrocytes perform many functions in the brain and spinal cord. Glucose metabolism is important for astroglial cells and astrocytes are the only cells with insulin receptors in the brain. The common antibiotic penicillin is also a chemical agent that causes degenerative effect on neuronal cell. The aim of this study is to show the effect of insulin and glucose at different concentrations on the astrocyte death induced by penicillin on primer astroglial cell line. It is well known that intracranial penicillin treatment causes neuronal cell death and it is used for experimental epilepsy model commonly. Previous studies showed that insulin and glucose might protect neuronal cell in case of proper concentrations. But, the present study is about the effect of insulin and glucose against astrocyte death induced by penicillin. For this purpose, newborn rat brain was extracted and then mechanically dissociated to astroglial cell suspension and finally grown in culture medium. Clutters were maintained for 2 weeks prior to being used in these experiments. Different concentrations of insulin (0, 1, 3 nM) and glucose (0, 3, 30 mM) were used in media without penicillin and with 2 500 μM penicillin. Penicillin decreased the viability of astroglial cell seriously. The highest cell viability appeared in medium with 3 nM insulin and 3 mM glucose but without penicillin. However, in medium with penicillin, the best cell survival was in medium with 1 nM insulin but without glucose. We concluded that insulin and glucose show protective effects on the damage induced by penicillin to primer astroglial cell line. Interestingly, cell survival depends on concentrations of insulin and glucose strongly. The results of this study will help to explain cerebrovascular pathologies parallel to insulin and glucose conditions of patient after intracranial injuries. PMID:25624816

1-[N, O-bis-(5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine (KN-62), an inhibitor of calcium-dependent camodulin protein kinase II, inhibits both insulin- and hypoxia-stimulated glucose transport in skeletal muscle.

PubMed Central

Brozinick, J T; Reynolds, T H; Dean, D; Cartee, G; Cushman, S W

1999-01-01

Previous studies have indicated a role for calmodulin in hypoxia-and insulin-stimulated glucose transport. However, since calmodulin interacts with multiple protein targets, it is unknown which of these targets is involved in the regulation of glucose transport. In the present study, we have used the calcium-dependent calmodulin protein kinase II (CAMKII) inhibitor 1-[N, O-bis-(5-isoquinolinesulphonyl) -N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) to investigate the possible role of this enzyme in the regulation of glucose transport in isolated rat soleus and epitrochlearis muscles. KN-62 did not affect basal 2-deoxyglucose transport, but it did inhibit both insulin- and hypoxia-stimulated glucose transport activity by 46 and 40% respectively. 1-[N,O-Bis-(1, 5-isoquinolinesulphonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-04), a structural analogue of KN-62 that does not inhibit CAMKII, had no effect on hypoxia-or insulin-stimulated glucose transport. Accordingly, KN-62 decreased the stimulated cell-surface GLUT4 labelling by a similar extent as the inhibition of glucose transport (insulin, 49% and hypoxia, 54%). Additional experiments showed that KN-62 also inhibited insulin- and hypoxia-stimulated transport by 37 and 40% respectively in isolated rat epitrochlearis (a fast-twitch muscle), indicating that the effect of KN-62 was not limited to the slow-twitch fibres of the soleus. The inhibitory effect of KN-62 on hypoxia-stimulated glucose transport appears to be specific to CAMKII, since KN-62 did not inhibit hypoxia-stimulated 45Ca efflux from muscles pre-loaded with 45Ca, or hypoxia-stimulated glycogen breakdown. Additionally, KN-62 affected neither insulin-stimulated phosphoinositide 3-kinase nor Akt activity, suggesting that the effects of KN-62 are not due to non-specific effects of this inhibitor on these regions of the insulin-signalling cascade. The results of the present study suggest that CAMKII might have a distinct role in insulin- and hypoxia-stimulated glucose transport, possibly in the vesicular trafficking of GLUT4. PMID:10215590

Simultaneous measurement of glucose transport and utilization in the human brain

PubMed Central

Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.

2011-01-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMRglc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMRglc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain. PMID:21791622

Research of transmissive near infrared spectroscopy for non-invasive blood glucose measurement

NASA Astrophysics Data System (ADS)

Yang, Wenming; Liao, Ningfang; Li, Yasheng; Shao, Liwei; Huang, Dehuang

2016-10-01

Near infrared (NIR) has prospectively applied in non-invasive blood glucose measurement due to glucose absorption among the 1.0-2.5m spectral bands. However, this significant technology is hard to be developed because of other blood components and low signal-to-noise ratio (SNR). In this work, we presented a non-invasive glucose measurement system using Fourier transform spectrometer which will work in fingertips or other human body tissues. A refrigerated InGaAs detector with high quantum efficiency performing well in the range of 1.0-1.7μm wavelength is used to acquire transmissive radiation. Preliminary experiment investigations were set up to test glucose levels of aqueous solutions with different concentrations. The analytical modeling of the interferogram data is based on arithmetic Fourier transform and supported by the curvilineal characterization. Experimental results show the variation of light intensity among different glucose concentrations and emphasize the obvious absorption of glucose in NIR wave-range. This study confirms the suitability that NIR can be developed in non-invasive glucose measurement.

Laboratory Exercise: Study of Digestive and Regulatory Processes through the Exploration of Fasted and Postprandial Blood Glucose

ERIC Educational Resources Information Center

Hopper, Mari K.; Maurer, Luke W.

2013-01-01

Digestive physiology laboratory exercises often explore the regulation of enzyme action rather than systems physiology. This laboratory exercise provides a systems approach to digestive and regulatory processes through the exploration of postprandial blood glucose levels. In the present exercise, students enrolled in an undergraduate animal…

Depletion of norepinephrine of the central nervous system Down-regulates the blood glucose level in d-glucose-fed and restraint stress models.

PubMed

Park, Soo-Hyun; Kim, Sung-Su; Lee, Jae-Ryeong; Sharma, Naveen; Suh, Hong-Won

2016-05-04

DSP-4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d-glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10-40μg) for 3days, and d-glucose (2g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120min after d-glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d-glucose-fed model. Plasma corticosterone level was downregulated in the d-glucose-fed model, whereas plasma insulin level increased in the d-glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d-glucose. In addition, the d-glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d-glucose-fed and restraint stress models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quick generation of Raman spectroscopy based in-process glucose control to influence biopharmaceutical protein product quality during mammalian cell culture.

PubMed

Berry, Brandon N; Dobrowsky, Terrence M; Timson, Rebecca C; Kshirsagar, Rashmi; Ryll, Thomas; Wiltberger, Kelly

2016-01-01

Mitigating risks to biotherapeutic protein production processes and products has driven the development of targeted process analytical technology (PAT); however implementing PAT during development without significantly increasing program timelines can be difficult. The development of a monoclonal antibody expressed in a Chinese hamster ovary (CHO) cell line via fed-batch processing presented an opportunity to demonstrate capabilities of altering percent glycated protein product. Glycation is caused by pseudo-first order, non-enzymatic reaction of a reducing sugar with an amino group. Glucose is the highest concentration reducing sugar in the chemically defined media (CDM), thus a strategy controlling glucose in the production bioreactor was developed utilizing Raman spectroscopy for feedback control. Raman regions for glucose were determined by spiking studies in water and CDM. Calibration spectra were collected during 8 bench scale batches designed to capture a wide glucose concentration space. Finally, a PLS model capable of translating Raman spectra to glucose concentration was built using the calibration spectra and spiking study regions. Bolus feeding in mammalian cell culture results in wide glucose concentration ranges. Here we describe the development of process automation enabling glucose setpoint control. Glucose-free nutrient feed was fed daily, however glucose stock solution was fed as needed according to online Raman measurements. Two feedback control conditions were executed where glucose was controlled at constant low concentration or decreased stepwise throughout. Glycation was reduced from ∼9% to 4% using a low target concentration but was not reduced in the stepwise condition as compared to the historical bolus glucose feeding regimen. © 2015 American Institute of Chemical Engineers.

Effect of intrapleural oxytocin injection on blood glucose level in rat (rattus norvegicous).

PubMed

Dezhkam, Y; Dezhkam, N

2014-01-01

The effect of Oxytocin on energy metabolism is still question. The aim of the present study was to investigate the effect of exogenous oxytocin injection in different dose and timetable on blood glucose level in rat. In this study 16 adult female rats were divided into 2 groups (Treatment 1(T1) and Treatment 2(T2)). T1 with 8 adult female rats received 0.2 IU/Kg oxytocin via intrapleural (IP) and blood glucose level was tested at 0th, 20th, 40th and 60th min after injection by collecting the blood from jugular vein. In T2 eight female rats received 0.4 IU/kg oxytocin via IP taking blood glucose measure at the same minutes as T1. The experiment tested in three replicates. Blood glucose meter (Model: 3TMSO1G) was used with glucose smart blood glucose monitoring system to the measurement of blood glucose level in rats. Data were analyzed using the GLM procedure of SAS (SAS, version 9) PDIFF was used to compare least square means among treatments adjusting by tukey test. There were hypoglycemic tendency in the changes of the blood glucose level in both T1 and T2, 20th min after injection (88.79 ± 3.28, 68.58 ± 3.63, respectively), while in the remaining subjects (4th and 60th min) blood glucose level increased (115.54 ± 4, 79.7 ± 2.09 and 136.33 ± 5.8, 123.54 ± 0.9, respectively). These results showed that blood glucose level in T1 significantly higher than T2 (p < 0.0001). These in vivo results showed that exogenous oxytocin can be good choice to decrease the blood glucose level very fast.

CAST/EiJ and C57BL/6J Mice Differ in Their Oral and Postoral Attraction to Glucose and Fructose.

PubMed

Sclafani, Anthony; Vural, Austin S; Ackroff, Karen

2017-03-01

A recent study indicated that CAST/EiJ and C57BL/6J mice differ in their taste preferences for maltodextrin but display similar sucrose preferences. The present study revealed strain differences in preferences for the constituent sugars of sucrose. Whereas B6 mice preferred 8% glucose to 8% fructose in 2-day tests, the CAST mice preferred fructose to glucose. These preferences emerged with repeated testing which suggested post-oral influences. In a second experiment, 2-day choice tests were conducted with the sugars versus a sucralose + saccharin (SS) mixture which is highly preferred in brief access tests. B6 mice strongly preferred glucose but not fructose to the non-nutritive SS whereas CAST mice preferred SS to both glucose and fructose even when food restricted. This implied that CAST mice are insensitive to the postoral appetite stimulating actions of the 2 sugars. A third experiment revealed, however, that intragastric glucose and fructose infusions conditioned significant but mild flavor preferences in CAST mice, whereas in B6 mice glucose conditioned a robust preference but fructose was ineffective. Thus, unlike other mouse strains and rats, glucose is not more reinforcing than fructose in CAST mice. Their oral preference for fructose over glucose may be related to a subsensitive maltodextrin receptor or glucose-specific receptor which is stimulated by glucose but not fructose. The failure of CAST mice to prefer glucose to a non-nutritive sweetener distinguishes this strain from other mouse strains and rats. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Testicular glucose and its transporter GLUT 8 as a marker of age-dependent variation and its role in steroidogenesis in mice.

PubMed

Banerjee, Arnab; Anuradha; Mukherjee, Kaustab; Krishna, Amitabh

2014-11-01

The present study evaluates the hypothesis, that glucose is essential for steroidogenesis and inadequate supply of glucose to the testis may be responsible for decline in steroidogenesis in mice during aging. Mice of different age groups (birth, weaning, puberty, reproductively active, and senescence) were utilized for this study. The changes in glucose, glucose transporter (GLUT), and insulin receptor (IR) level in the testis were evaluated and compared with the testicular steroidogenic parameters such as steroidogenic acute regulatory protein (StAR), 3β-hydroxy steroid dehydrogenase (3β-HSD) and circulating testosterone levels. The result showed significant correlation between changes in GLUT 8 and glucose levels with changes in StAR level in the testis and circulating testosterone level in the mice from birth to senescence. Immunohistochemical analysis showed intense immunostaining of GLUT 8 and IR in the interstitial cells, most likely Leydig cells, in testis of pubertal and reproductively active mice suggesting their relevance in steroidogenesis. The in vitro study showed a significant positive correlation between luteinizing hormone (LH)-induced increase in GLUT 8 and StAR (r = 0.82; P < 0.05) proteins level in the testes with increase in testosterone (r = 0.97; P < 0.05) synthesis of reproductively active mice. This study also showed increased release of lactate with increased uptake of glucose by the testis. Further, intra-testicular treatment of 2-deoxy glucose, to reproductively active mice caused a significant decrease in 3β-HSD enzyme activity in the testis. Based on these findings, it may be concluded that the changes in glucose level either directly or indirectly lead to changes in testicular steroidogenesis during aging. © 2014 Wiley Periodicals, Inc.

Assessing oral candidal carriage with mixed salivary glucose levels as non-invasive diagnostic tool in type-2 diabetics of davangere, karnataka, India.

PubMed

Naik, Rashmi; Mujib B R, Ahmed; Raaju, U R; Telagi, Neethu

2014-07-01

The health of oral tissues is known to be related to salivary flow and its composition which may be altered in diabetic patients. The purpose of this study is to correlate mixed salivary glucose levels and oral candidal carriage and to assess the prevalence of candidal carriage in diabetics and controls. Thirty adults with type-2 diabetes and 30 without diabetes (control subjects), aged 30-60 yr, participated in the study. Unstimulated saliva was collected and investigated for glucose levels (using glucose oxidase method) and colony-forming units (CFU) of Candida, this was stained with two stains, periodic acid-schiff stain and Grocott Gomori stain. In the present study mixed salivary glucose concentration in diabetics was significantly higher (p<0.01) compared to the controls. Diabetics with intraoral candidal carriage had higher salivary glucose levels (mean = 12.76±5.85 mg/dl) compared to cases where Candida was not isolated. The diabetics without intraoral candidal carriage had lower salivary glucose levels (mean = 5.36±2.24 mg/dl). This relationship could be seen in controls (non-diabetics) also. Diabetics showed an oral candidal carriage rate of 80% which was significantly higher compared to nondiabetics who showed an oral candidal carriage rate of 40%. Mixed salivary glucose levels were significantly higher in diabetics. The possible high salivary glucose level could predispose to oral candidal infection. So saliva can be used as a quick, non-invasive tool to assess the oral candidal status and possible infection.

Endothelin-1 regulation is entangled in a complex web of epigenetic mechanisms in diabetes.

PubMed

Biswas, S; Feng, B; Thomas, A; Chen, S; Aref-Eshghi, E; Sadikovic, B; Chakrabarti, S

2018-06-27

Endothelial cells (ECs) are primary targets of glucose-induced tissue damage. As a result of hyperglycemia, endothelin-1 (ET-1) is upregulated in organs affected by chronic diabetic complications. The objective of the present study was to identify novel transcriptional mechanisms that influence ET-1 regulation in diabetes. We carried out the investigation in microvascular ECs using multiple approaches. ECs were incubated with 5 mM glucose (NG) or 25 mM glucose (HG) and analyses for DNA methylation, histone methylation, or long non-coding RNA- mediated regulation of ET-1 mRNA were then performed. DNA methylation array analyses demonstrated the presence of hypomethylation in the proximal promoter and 5' UTR/first exon regions of EDN1 following HG culture. Further, globally blocking DNA methylation or histone methylation significantly increased ET-1 mRNA expressions in both NG and HG-treated HRECs. While, knocking down the pathogenetic lncRNAs ANRIL, MALAT1, and ZFAS1 subsequently prevented the glucose-induced upregulation of ET-1 transcripts. Based on our past and present findings, we present a novel paradigm that reveals a complex web of epigenetic mechanisms regulating glucose-induced transcription of ET-1. Improving our understanding of such processes may lead to better targeted therapies.

A RADIOAUTOGRAPHIC STUDY OF GLYCERIDE SYNTHESIS IN VIVO DURING INTESTINAL ABSORPTION OF FATS AND LABELED GLUCOSE

PubMed Central

Jersild, Ralph A.

1966-01-01

Radioautography was used to detect the synthesis of labeled glycerides in intestinal absorptive cells following injections of fatty chyme and glucose-6-H3 into ligated segments of upper jejunum of fasting rats. Absorption intervals ranged from 2 to 20 min. Labeling is evident throughout the cells in as short a time as 2 min. Most grains are present over droplets of absorbed fat beginning with those in the endoplasmic reticulum immediately subjacent to the terminal web. With longer absorption periods, frequent grains are present over accumulations of fat droplets in the Golgi cisternae and intercellular spaces. A similar pattern of grains is seen following absorption of either linoleic acid or safflower oil. By comparison, considerably less label is present in the cells when the fat is extracted with alcohol prior to radioautographic procedures, or when labeled glucose alone is absorbed. A significant incorporation of glucose label into newly synthesized glycerides is indicated and confirmed by scintillation counts on saponified lipid extracts. The grain distribution implies an involvement of the extreme apical endoplasmic reticulum in this synthesis. PMID:5971642

Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity

PubMed Central

Nahar, Laizuman; Nasrin, Fatema; Zahan, Ronok; Haque, Anamul; Haque, Ekramul; Mosaddik, Ashik

2014-01-01

Background: Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. Objective: The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). Materials and Methods: Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. Results: There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. Conclusion: These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress. PMID:24761124

Multisite Study of an Implanted Continuous Glucose Sensor Over 90 Days in Patients With Diabetes Mellitus.

PubMed

Dehennis, Andrew; Mortellaro, Mark A; Ioacara, Sorin

2015-07-29

Continuous glucose monitoring (CGM), which enables real-time glucose display and trend information as well as real-time alarms, can improve glycemic control and quality of life in patients with diabetes mellitus. Previous reports have described strategies to extend the useable lifetime of a single sensor from 1-2 weeks to 28 days. The present multisite study describes the characterization of a sensing platform achieving 90 days of continuous use for a single, fully implanted sensor. The Senseonics CGM system is composed of a long-term implantable glucose sensor and a wearable smart transmitter. Study subjects underwent subcutaneous implantation of sensors in the upper arm. Eight-hour clinic sessions were performed every 14 days, during which sensor glucose values were compared against venous blood lab reference measurements collected every 15 minutes using mean absolute relative differences (MARDs). All subjects (mean ± standard deviation age: 43.5 ± 11.0 years; with 10 sensors inserted in men and 14 in women) had type 1 diabetes mellitus. Most (22 of 24) sensors reported glucose values for the entire 90 days. The MARD value was 11.4 ± 2.7% (range, 8.1-19.5%) for reference glucose values between 40-400 mg/dl. There was no significant difference in MARD throughout the 90-day study (P = .31). No serious adverse events were noted. The Senseonics CGM, composed of an implantable sensor, external smart transmitter, and smartphone app, is the first system that uses a single sensor for continuous display of accurate glucose values for 3 months. © 2015 Diabetes Technology Society.

Single Cell "Glucose Nanosensor" Verifies Elevated Glucose Levels in Individual Cancer Cells.

PubMed

Nascimento, Raphael A S; Özel, Rıfat Emrah; Mak, Wai Han; Mulato, Marcelo; Singaram, Bakthan; Pourmand, Nader

2016-02-10

Because the transition from oxidative phosphorylation to anaerobic glycolytic metabolism is a hallmark of cancer progression, approaches to identify single living cancer cells by their unique glucose metabolic signature would be useful. Here, we present nanopipettes specifically developed to measure glucose levels in single cells with temporal and spatial resolution, and we use this technology to verify the hypothesis that individual cancer cells can indeed display higher intracellular glucose levels. The nanopipettes were functionalized as glucose nanosensors by immobilizing glucose oxidase (GOx) covalently to the tip so that the interaction of glucose with GOx resulted in a catalytic oxidation of β-d-glucose to d-gluconic acid, which was measured as a change in impedance due to drop in pH of the medium at the nanopipette tip. Calibration studies showed a direct relationship between impedance changes at the tip and glucose concentration in solution. The glucose nanosensor quantified single cell intracellular glucose levels in human fibroblasts and the metastatic breast cancer lines MDA-MB-231 and MCF7 and revealed that the cancer cells expressed reproducible and reliable increases in glucose levels compared to the nonmalignant cells. Nanopipettes allow repeated sampling of the same cell, as cells remain viable during and after measurements. Therefore, nanopipette-based glucose sensors provide an approach to compare changes in glucose levels with changes in proliferative or metastatic state. The platform has great promise for mechanistic investigations, as a diagnostic tool to distinguish cancer cells from nonmalignant cells in heterogeneous tissue biopsies, as well as a tool for monitoring cancer progression in situ.

Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults.

PubMed

Riby, Leigh M; McLaughlin, Jennifer; Riby, Deborah M; Graham, Cheryl

2008-11-01

Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addition, risk factors associated with the development of poor glucose regulation in middle-aged adults were considered. In a repeated measures design, thirty-three middle-aged adults (aged 35-55 years) performed a battery of memory and non-memory tasks after either 25 g or 50 g glucose or a sweetness matched placebo drink. To assess the impact of individual differences in glucose regulation, blood glucose measurements were taken on four occasions during testing. A lifestyle and diet questionnaire was also administered. Consistent with previous research, episodic memory ability benefited from glucose ingestion when task demands were high. Blood glucose concentration was also found to predict performance across a number of cognitive domains. Interestingly, the risk factors associated with poor glucose regulation were linked to dietary impacts traditionally associated with poor health, e.g. the consumption of high-sugar sweets and drinks. The research replicates earlier work suggesting that task demands are critical to the glucose facilitation effect. Importantly, the data demonstrate clear associations between elevated glycaemia and relatively poor cognitive performance, which may be partly due to the effect of dietary and lifestyle factors.

Effects of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in bovine mammary epithelial cells.

PubMed

Liu, Hongyun; Zhao, Ke; Liu, Jianxin

2013-01-01

As the main precursor for lactose synthesis, large amounts of glucose are required by lactating dairy cows. Milk yield greatly depends on mammary lactose synthesis due to its osmoregulatory property for mammary uptake of water. Thus, glucose availability to the mammary gland could be a potential regulator of milk production. In the present study, the effect of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in vitro was investigated. Bovine mammary epithelial cells (BMEC) were treated for 12 h with various concentrations of glucose (2.5, 5, 10 or 20 mmol/L). The higher concentrations of glucose (10-20 mmol/L) did not affect the mRNA expression of acetyl-CoA carboxylase, diacyl glycerol acyl transferase, glycerol-3 phosphate acyl transferase and α-lactalbumin, whereas fatty acid synthase, sterol regulatory element binding protein-1 and beta-1, 4-galactosyl transferase mRNA expression increased at 10 mmol/L and then decreased at 20 mmol/L. The content of lactose synthase increased with increasing concentration of glucose, with addition of highest value at 20 mmol/L of glucose. Moreover, the increased glucose concentration stimulated the activities of pyruvate kinase and glucose-6-phosphate dehydrogenase, and elevated the energy status of the BMEC. Therefore, it was deduced that after increasing glucose availability, the extra absorbed glucose was partitioned to entering the synthesis of milk fat and lactose by the regulation of the mRNA expression of key genes, promoting glucose metabolism by glycolysis and pentose phosphate pathway as well as energy status. These results indicated that the sufficient availability of glucose in BMEC may promote glucose metabolism, and affect the synthesis of milk composition.

Biosensor based on glucose oxidase-nanoporous gold co-catalysis for glucose detection.

PubMed

Wu, Chao; Sun, Huihui; Li, Yufei; Liu, Xueying; Du, Xiaoyu; Wang, Xia; Xu, Ping

2015-04-15

Promoting the electrocatalytic oxidation of glucose is crucial in glucose biosensor design. In this study, nanoporous gold (NPG) was selected for glucose oxidase (GOx) immobilization and glucose biosensor fabrication because of its open, highly conductive, biocompatible, and interconnected porous structure, which also facilitates the electrocatalytic oxidation of glucose. The electrochemical reaction on the surface of the resulting GOx/NPG/GCE bioelectrode was attributed to the co-catalysis effect of GOx and NPG. A surface-confined reaction in a phosphate buffer solution was observed at the bioelectrode during cyclic voltammetry experiments. Linear responses were observed for large glucose concentrations ranging from 50μM to 10mM, with a high sensitivity of 12.1μAmM(-1)cm(-2) and a low detection limit of 1.02μM. Furthermore, the GOx/NPG/GCE bioelectrode presented strong anti-interference capability against cholesterol, urea, tributyrin, ascorbic acid, and uric acid, along with a long shelf-life. For the detection of glucose in human serum, the data generated by the GOx/NPG/GCE bioelectrode were in good agreement with those produced by an automatic biochemical analyzer. These unique properties make the GOx/NPG/GCE bioelectrode an excellent choice for the construction of a glucose biosensor. Copyright © 2014 Elsevier B.V. All rights reserved.

IR-IR Conformation Specific Spectroscopy of Na+(Glucose) Adducts

NASA Astrophysics Data System (ADS)

Voss, Jonathan M.; Kregel, Steven J.; Fischer, Kaitlyn C.; Garand, Etienne

2018-01-01

We report an IR-IR double resonance study of the structural landscape present in the Na+(glucose) complex. Our experimental approach involves minimal modifications to a typical IR predissociation setup, and can be carried out via ion-dip or isomer-burning methods, providing additional flexibility to suit different experimental needs. In the current study, the single-laser IR predissociation spectrum of Na+(glucose), which clearly indicates contributions from multiple structures, was experimentally disentangled to reveal the presence of three α-conformers and five β-conformers. Comparisons with calculations show that these eight conformations correspond to the lowest energy gas-phase structures with distinctive Na+ coordination. [Figure not available: see fulltext.

Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model

PubMed Central

Kim, Chea-Ha

2015-01-01

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level. PMID:25792867

Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model.

PubMed

Kim, Chea-Ha; Hong, Jae-Seung

2015-03-01

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level.

Quantification of Quercetin Obtained from Allium cepa Lam. Leaves and its Effects on Streptozotocin-induced Diabetic Neuropathy.

PubMed

Dureshahwar, Khan; Mubashir, Mohammed; Une, Hemant Devidas

2017-01-01

Antioxidant potential has protective effects in diabetic neuropathy (DN); hence, the present study was designed with an objective to quantify quercetin from shade-dried leaves of Allium cepa Lam. and to study its effects on streptozotocin (STZ)-induced chronic DN. The shade-dried leaves of A. cepa Lam. were extracted with methanol and then fractionated using ethyl acetate (ACEA). The quantification of quercetin in ACEA was evaluated by high-performance thin layer chromatography (HPTLC). The STZ (40 mg/kg) was administered to Sprague-Dawley rats (180-250 g) maintained at normal housing conditions. The STZ was administered once a day for 3 consecutive days. The elevation in blood glucose was monitored for 3 weeks periodically using flavin adenine dinucleotide-glucose dehydrogenase method by Contour TS glucometer. Rats showing blood glucose above 250 mg/dl were selected for the study. Animals were divided into eight groups. ACEA (25, 50, and 100 mg/kg), quercetin (40 mg/kg), metformin (120 mg/kg), and gabapentin (100 mg/kg) were given orally once a day for 2 weeks. The blood glucose level was again measured at the end of treatment to assess DN. Thermal hyperalgesia, cold allodynia, motor incoordination, and neurotoxicity were studied initially and at the end of 2-week treatment. Biochemical parameters were also evaluated after 2-week drug treatment. The quercetin present in ACEA was 4.82% by HPTLC. All the ACEA treatment reduces blood glucose level at the end of the 2-week study and shows a significant neuroprotective effect in STZ-induced DN in the above experimental models. The quercetin present in ACEA proved protective effect in STZ-induced DN. High-performance thin layer chromatography reveals the presence of 4.82% quercetin in Allium cepa ethyl acetate. (ACEA). Its investigation against various diabetic neuropathy biomarkers has proved that ACEA has significant blood glucose reducing action shown neuroprotective action in thermal hyperalgesia, motor incoordination, and biochemical parameters. Abbreviations Used : HPTLC: High-performance thin layer chromatography, TLC: Thin layer chromatography, UV: Ultraviolet, ACEA: Allium cepa ethyl acetate, STZ: Streptozotocin, LDL: Low-density lipids, HDL: High-density lipids.

Analysis Article on the Performance Analysis of the OneTouch® UltraVue™ Blood Glucose Monitoring System

PubMed Central

Solnica, Bogdan

2009-01-01

In this issue of Journal of Diabetes Science and Technology, Chang and colleagues present the analytical performance evaluation of the OneTouch® UltraVue™ blood glucose meter. This device is an advanced construction with a color display, used-strip ejector, no-button interface, and short assay time. Accuracy studies were performed using a YSI 2300 analyzer, considered the reference. Altogether, 349 pairs of results covering a wide range of blood glucose concentrations were analyzed. Patients with diabetes performed a significant part of the tests. Obtained results indicate good accuracy of OneTouch UltraVue blood glucose monitoring system, satisfying the International Organization for Standardization recommendations and thereby locating >95% of tests within zone A of the error grid. Results of the precision studies indicate good reproducibility of measurements. In conclusion, the evaluation of the OneTouch UltraVue meter revealed good analytical performance together with convenient handling useful for self-monitoring of blood glucose performed by elderly diabetes patients. PMID:20144432

Analysis article on the performance analysis of the OneTouch UltraVue blood glucose monitoring system.

PubMed

Solnica, Bogdan

2009-09-01

In this issue of Journal of Diabetes Science and Technology, Chang and colleagues present the analytical performance evaluation of the OneTouch UltraVue blood glucose meter. This device is an advanced construction with a color display, used-strip ejector, no-button interface, and short assay time. Accuracy studies were performed using a YSI 2300 analyzer, considered the reference. Altogether, 349 pairs of results covering a wide range of blood glucose concentrations were analyzed. Patients with diabetes performed a significant part of the tests. Obtained results indicate good accuracy of OneTouch UltraVue blood glucose monitoring system, satisfying the International Organization for Standardization recommendations and thereby locating >95% of tests within zone A of the error grid. Results of the precision studies indicate good reproducibility of measurements. In conclusion, the evaluation of the OneTouch UltraVue meter revealed good analytical performance together with convenient handling useful for self-monitoring of blood glucose performed by elderly diabetes patients. 2009 Diabetes Technology Society.

Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study.

PubMed

Yellapu, Nanda Kumar; Kandlapalli, Kalpana; Valasani, Koteswara Rao; Sarma, P V G K; Matcha, Bhaskar

2013-01-01

Glucokinase (GK) is the predominant hexokinase that acts as glucose sensor and catalyses the formation of Glucose-6-phosphate. The mutations in GK gene influence the affinity for glucose and lead to altered glucose levels in blood causing maturity onset diabetes of the young type 2 (MODY2) condition, which is one of the prominent reasons of type 2 diabetic condition. In view of the importance of mutated GK resulting in hyperglycemic condition, in the present study, molecular dynamics simulations were carried out in intact and 256 E-K mutated GK structures and their energy values and conformational variations were correlated. Energy variations were observed in mutated GK (3500 Kcal/mol) structure with respect to intact GK (5000 Kcal/mol), and it showed increased γ -turns, decreased β -turns, and more helix-helix interactions that affected substrate binding region where its volume increased from 1089.152 Å(2) to 1246.353 Å(2). Molecular docking study revealed variation in docking scores (intact = -12.199 and mutated = -8.383) and binding mode of glucose in the active site of mutated GK where the involvement of A53, S54, K56, K256, D262 and Q286 has resulted in poor glucose binding which probably explains the loss of catalytic activity and the consequent prevailing of high glucose levels in MODY2 condition.

Subjects with Impaired Fasting Glucose: Evolution in a Period of 6 Years

PubMed Central

Leiva, E.; Mujica, V.; Orrego, R.; Wehinger, S.; Soto, A.; Icaza, G.; Vásquez, M.; Díaz, L.; Andrews, M.; Arredondo, M.

2014-01-01

Aim. To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. Methods. We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Results. Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. Conclusion. The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients. PMID:25215305

Epigallocatechin-3-gallate ameliorates insulin resistance in hepatocytes.

PubMed

Ma, Shan-Bo; Zhang, Rui; Miao, Shan; Gao, Bin; Lu, Yang; Hui, Sen; Li, Long; Shi, Xiao-Peng; Wen, Ai-Dong

2017-06-01

Hyperglycemia is a typical pathogenic factor in a series of complications among patients with type II diabetes. Epigallocatechin-3-gallate (EGCG) is the major polyphenol extracted from green tea and is reported to be an antioxidant. The aim of the present study was to examine the effect of EGCG on insulin resistance in human HepG2 cells pretreated with high concentrations of glucose. The protein kinase B (AKT)/glycogen synthase kinase (GSK) pathways were analyzed using western blot analysis in HepG2 cells and primary mouse hepatocytes treated with high glucose and/or EGCG. Cellular glycogen content was determined using a glycogen assay kit. Reactive oxygen species (ROS) production was determined using dihydroethidium staining and flow cytometry. c‑JUN N‑terminal kinase (JNK)/insulin receptor substrate 1 (IRS1)/AKT/GSK signaling was explored using western blot analysis in HepG2 cells treated with high glucose and/or EGCG or N-acetyl-cysteine. High glucose significantly decreased the levels of phosphorylated AKT and GSK in HepG2 cells and mouse primary hepatocytes. Pretreatment with EGCG significantly restored the activation of AKT and GSK in HepG2 cells and primary hepatocytes exposed to high glucose. In HepG2 cells and primary hepatocytes, glycogen synthesis was improved by EGCG treatment in a dose‑dependent manner. High glucose significantly stimulated the production of ROS while EGCG protected high glucose‑induced ROS production. ROS is known to serve a major role in high glucose induced‑insulin resistance by increasing JNK and IRS1 serine phosphorylation. In the present study, EGCG was observed to enhance the insulin‑signaling pathway. EGCG ameliorated high glucose‑induced insulin resistance in the hepatocytes by potentially decreasing ROS‑induced JNK/IRS1/AKT/GSK signaling.

The impact of transsphenoidal surgery on glucose homeostasis and insulin resistance in acromegaly.

PubMed

Stelmachowska-Banaś, Maria; Zieliński, Grzegorz; Zdunowski, Piotr; Podgórski, Jan; Zgliczyński, Wocjiech

2011-01-01

Impaired glucose tolerance and overt diabetes mellitus are frequently associated with acro-megaly. The aim of this study was to find out whether these alterations could be reversed after transsphenoidal surgery. Two hundred and thirty-nine acromegalic patients were studied before and 6-12 months after transsphenoidal surgery. Diagnosis of active acromegaly was established on the basis of widely recognized criteria. In each patient, glucose and insulin concentrations were assessed during the 75 γ oral glucose tolerance test (OGTT). To estimate insulin resistance, we used homeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). At the moment of diagnosis, diabetes mellitus was present in 25% of the acromegalic patients. After surgery, the pre-valence of diabetes mellitus normalized to the level present in the general Polish population. We found a statistically significant reduction after surgery in plasma glucose levels both fasting (89.45 ± 13.92 mg/dL vs. 99.12 ± 17.33 mg/dL, p < 0.001) and during OGTT. Similarly, a prominent reduction in insulin secretion was found after surgery compared to the moment of diagnosis (15.44 ± 8.80 mIU/mL vs. 23.40 ± 10.24 mIU/mL, p < 0.001). After transsphenoidal surgery, there was a significant reduction in HOMA-IR (3.08 vs. 6.76, p < 0.0001) and a significant increase in QUICKI (0.32 vs. 0.29, p < 0.001). There were no statistically significant differences after surgery in fasting glucose and insulin levels between patients with controlled and in-adequately controlled disease. We conclude that in acromegalic patients glucose homeostasis alterations and insulin sensitivity can be normalized after transsphenoidal surgery, even if strict biochemical cure criteria are not fulfilled.

Applications of 2-deoxy-2-fluoro-D-glucose (FDG) in Plant Imaging: Past, Present, and Future

PubMed Central

Fatangare, Amol; Svatoš, Aleš

2016-01-01

The aim of this review article is to explore and establish the current status of 2-deoxy-2-fluoro-D-glucose (FDG) applications in plant imaging. In the present article, we review the previous literature on its experimental merits to formulate a consistent and inclusive picture of FDG applications in plant-imaging research. 2-deoxy-2-fluoro-D-glucose is a [18F]fluorine-labeled glucose analog in which C-2 hydroxyl group has been replaced by a positron-emitting [18F] radioisotope. As FDG is a positron-emitting radiotracer, it could be used in in vivo imaging studies. FDG mimics glucose chemically and structurally. Its uptake and distribution are found to be similar to those of glucose in animal models. FDG is commonly used as a radiotracer for glucose in medical diagnostics and in vivo animal imaging studies but rarely in plant imaging. Tsuji et al. (2002) first reported FDG uptake and distribution in tomato plants. Later, Hattori et al. (2008) described FDG translocation in intact sorghum plants and suggested that it could be used as a tracer for photoassimilate translocation in plants. These findings raised interest among other plant scientists, which has resulted in a recent surge of articles involving the use of FDG as a tracer in plants. There have been seven studies describing FDG-imaging applications in plants. These studies describe FDG applications ranging from monitoring radiotracer translocation to analyzing solute transport, root uptake, photoassimilate tracing, carbon allocation, and glycoside biosynthesis. Fatangare et al. (2015) recently characterized FDG metabolism in plants; such knowledge is crucial to understanding and validating the application of FDG in plant imaging research. Recent FDG studies significantly advance our understanding of FDG translocation and metabolism in plants but also raise new questions. Here, we take a look at all the previous results to form a comprehensive picture of FDG translocation, metabolism, and applications in plants. In conclusion, we summarize current knowledge, discuss possible implications and limitations of previous studies, point to open questions in the field, and comment on the outlook for FDG applications in plant imaging. PMID:27242806

Applications of 2-deoxy-2-fluoro-D-glucose (FDG) in Plant Imaging: Past, Present, and Future.

PubMed

Fatangare, Amol; Svatoš, Aleš

2016-01-01

The aim of this review article is to explore and establish the current status of 2-deoxy-2-fluoro-D-glucose (FDG) applications in plant imaging. In the present article, we review the previous literature on its experimental merits to formulate a consistent and inclusive picture of FDG applications in plant-imaging research. 2-deoxy-2-fluoro-D-glucose is a [(18)F]fluorine-labeled glucose analog in which C-2 hydroxyl group has been replaced by a positron-emitting [(18)F] radioisotope. As FDG is a positron-emitting radiotracer, it could be used in in vivo imaging studies. FDG mimics glucose chemically and structurally. Its uptake and distribution are found to be similar to those of glucose in animal models. FDG is commonly used as a radiotracer for glucose in medical diagnostics and in vivo animal imaging studies but rarely in plant imaging. Tsuji et al. (2002) first reported FDG uptake and distribution in tomato plants. Later, Hattori et al. (2008) described FDG translocation in intact sorghum plants and suggested that it could be used as a tracer for photoassimilate translocation in plants. These findings raised interest among other plant scientists, which has resulted in a recent surge of articles involving the use of FDG as a tracer in plants. There have been seven studies describing FDG-imaging applications in plants. These studies describe FDG applications ranging from monitoring radiotracer translocation to analyzing solute transport, root uptake, photoassimilate tracing, carbon allocation, and glycoside biosynthesis. Fatangare et al. (2015) recently characterized FDG metabolism in plants; such knowledge is crucial to understanding and validating the application of FDG in plant imaging research. Recent FDG studies significantly advance our understanding of FDG translocation and metabolism in plants but also raise new questions. Here, we take a look at all the previous results to form a comprehensive picture of FDG translocation, metabolism, and applications in plants. In conclusion, we summarize current knowledge, discuss possible implications and limitations of previous studies, point to open questions in the field, and comment on the outlook for FDG applications in plant imaging.

Flow enthalpimetric determination of glucose, based on oxidation by 1,4-benzoquinone and use of an immobilized glucose oxidase column.

PubMed

Kiba, N; Tomiyasu, T; Furusawa, M

1984-02-01

A flow enthalpimetric method for the determination of glucose is presented. The method is based on the reaction of glucose with 1,4-benzoquinone in the presence of immobilized glucose oxidase. d-Glucose concentrations ranging from 0.02 to 75mM can be determined. The method is applicable to the determination of glucose in soft drinks, wines, beers, jams and serum.

High glucose induces inflammatory cytokine through protein kinase C-induced toll-like receptor 2 pathway in gingival fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Shao-Yun, E-mail: jiangshaoyun@yahoo.com; Wei, Cong-Cong; Shang, Ting-Ting

2012-10-26

Highlights: Black-Right-Pointing-Pointer High glucose significantly induced TLR2 expression in gingival fibroblasts. Black-Right-Pointing-Pointer High glucose increased NF-{kappa}B p65 nuclear activity, IL-1{beta} and TNF-{alpha} levels. Black-Right-Pointing-Pointer PKC-{alpha}/{delta}-TLR2 pathway is involved in periodontal inflammation under high glucose. -- Abstract: Toll-like receptors (TLRs) play a key role in innate immune response and inflammation, especially in periodontitis. Meanwhile, hyperglycemia can induce inflammation in diabetes complications. However, the activity of TLRs in periodontitis complicated with hyperglycemia is still unclear. In the present study, high glucose (25 mmol/l) significantly induced TLR2 expression in gingival fibroblasts (p < 0.05). Also, high glucose increased nuclear factor kappa B (NF-{kappa}B)more » p65 nuclear activity, tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-l{beta} (IL-1{beta}) levels. Protein kinase C (PKC)-{alpha} and {delta} knockdown with siRNA significantly decreased TLR2 and NF-{kappa}B p65 expression (p < 0.05), whereas inhibition of PKC-{beta} had no effect on TLR2 and NF-{kappa}B p65 under high glucose (p < 0.05). Additional studies revealed that TLR2 knockdown significantly abrogated high-glucose-induced NF-{kappa}B expression and inflammatory cytokine secretion. Collectively, these data suggest that high glucose stimulates TNF-{alpha} and IL-1{beta} secretion via inducing TLR2 through PKC-{alpha} and PKC-{delta} in human gingival fibroblasts.« less

Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes.

PubMed

Winter, Theresa; Hannemann, Anke; Suchsland, Juliane; Nauck, Matthias; Petersmann, Astrid

2018-03-12

Measuring the glucose concentration in whole blood samples is critical due to unsatisfactory glycolysis inhibition. Previous studies showed that Terumo tubes were superior, but they were taken off the European market in 2016 and alternatives were required. This initiated the present evaluation of glucose stability in five available tube types. Venous blood samples were collected from 61 healthy volunteers to test tubes supplied by Terumo (two sets), Greiner FC-Mix, BD FX-Mixture and BD serum. After sampling, the contents were thoroughly mixed and centrifuged within an hour. The glucose concentrations were determined and the samples resuspended except for BD serum tubes (gel barrier). The first 30 samples were stored at room temperature and the remaining 31 at 4°C. After 24, 48, 72 and 96 h, all tubes were (re)centrifuged, and glucose concentration measurements were repeated. Changes in glucose concentrations over time differed significantly between the investigated tube types and to a certain extent between the two storing conditions. Glycolysis was most evident in the BD FX-mixture tubes. Good glucose stability was observed in samples retrieved form BD serum and Greiner tubes. The stability in both Terumo tubes was comparable to that in other studies. Although Greiner and both Terumo tubes are supposed to contain the same glycolysis inhibitor, glucose stability differed between these tubes. We showed that Greiner is an acceptable alternative to Terumo and that glucose in serum that was rapidly separated from corpuscles by a gel barrier is stable for an extended time.

In Vivo and Ex Vivo Transcutaneous Glucose Detection Using Surface-Enhanced Raman Spectroscopy

NASA Astrophysics Data System (ADS)

Ma, Ke

Diabetes mellitus is widely acknowledged as a large and growing health concern. The lack of practical methods for continuously monitoring glucose levels causes significant difficulties in successful diabetes management. Extensive validation work has been carried out using surface-enhanced Raman spectroscopy (SERS) for in vivo glucose sensing. This dissertation details progress made towards a Raman-based glucose sensor for in vivo, transcutaneous glucose detection. The first presented study combines spatially offset Raman spectroscopy (SORS) with SERS (SESORS) to explore the possibility of in vivo, transcutaneous glucose sensing. A SERS-based glucose sensor was implanted subcutaneously in Sprague-Dawley rats. SERS spectra were acquired transcutaneously and analyzed using partial least-squares (PLS). Highly accurate and consistent results were obtained, especially in the hypoglycemic range. Additionally, the sensor demonstrated functionality at least17 days after implantation. A subsequent study further extends the application of SESORS to the possibility of in vivo detection of glucose in brain through skull. Specifically, SERS nanoantennas were buried in an ovine tissue behind a bone with 8 mm thickness and detected by using SESORS. In addition, quantitative detection through bones by using SESORS was also demonstrated. A device that could measure glucose continuously as well as noninvasively would be of great use to patients with diabetes. The inherent limitation of the SESORS approach may prevent this technique from becoming a noninvasive method. Therefore, the prospect of using normal Raman spectroscopy for glucose detection was re-examined. Quantitative detection of glucose and lactate in the clinically relevant range was demonstrated by using normal Raman spectroscopy with low power and short acquisition time. Finally, a nonlinear calibration method called least-squares support vector machine regression (LS-SVR) was investigated for analyzing spectroscopic data sets of glucose detection. Comparison studies were demonstrated between LS-SVR and PLS. LS-SVR demonstrated significant improvements in accuracy over PLS for glucose detection, especially when a global calibration model was required. The improvements imparted by LS-SVR open up the possibility of developing an accurate prediction algorithm for Raman-based glucose sensing applicable to a large human population. Overall, these studies show the high promise held by the Raman-based sensor for the challenge of optimal glycemic control.

Metabolism of D-[1-3H]glucose, D-[2-3H]glucose, D-[5-3H]glucose, D-[6-3H]glucose and D-[U-14C]glucose by rat and human erythrocytes incubated in the presence of H2O or D2O.

PubMed

Conget, I; Malaisse, W J

1995-02-01

The present study investigates whether heavy water affects the efficiency of 3HOH production from D-[1-3H]glucose, D-[2-3H]glucose, D-[5-3H]glucose and D-[6-3H]glucose relative to the total generation of tritiated metabolites produced by either rat or human erythrocytes. The relative 3HOH yield was close to 95% with D-[5-3H]glucose, 72% with D-[2-3H]glucose, 22-32% with D-[1-3H]glucose, and only 12% with D-[6-3H]glucose. In the latter case, the comparison of the specific radioactivity of intracellular and extracellular acidic metabolites, expressed relative to that of 14C-labelled metabolites produced from D-[U-14C]glucose, indicated that the generation of 3HOH from D-[6-3H]glucose occurs at distal metabolic steps, such as the partial reversion of the pyruvate kinase reaction or the interconversion of pyruvate and L-alanine in the reaction catalysed by glutamate-pyruvate transaminase. As a rule, the substitution of H2O by D2O only caused minor to negligible changes in the relative 3HOH yield. This implies that the unexpectedly high deuteration of 13C-labelled D-glucose metabolites recently documented in erythrocytes exposed to D2O cannot be attributed to any major interference of heavy water with factors regulating both the deuteration and detritiation efficiency, such as the enzyme-to-enzyme tunnelling of specific glycolytic intermediates.

Simultaneous measurement of glucose transport and utilization in the human brain.

PubMed

Shestov, Alexander A; Emir, Uzay E; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R; Öz, Gülin

2011-11-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, K(M)(t) and V(max)(t), in humans have so far been obtained by measuring steady-state brain glucose levels by proton ((1)H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMR(glc)) obtained from other tracer studies, such as (13)C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state (1)H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMR(glc), this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain.

Gender Differences of Brain Glucose Metabolic Networks Revealed by FDG-PET: Evidence from a Large Cohort of 400 Young Adults

PubMed Central

Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Background Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. Materials and Methods FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25∼45 years, mean age±SD: 40.9±3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Results Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. Conclusion This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients. PMID:24358312

Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

PubMed

Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

Glucose-6-phosphate dehydrogenase deficiency presented with convulsion: a rare case.

PubMed

Merdin, Alparslan; Avci, Fatma; Guzelay, Nihal

2014-01-29

Red blood cells carry oxygen in the body and Glucose-6-Phosphate Dehydrogenase protects these cells from oxidative chemicals. If there is a lack of Glucose-6-Phosphate Dehydrogenase, red blood cells can go acute hemolysis. Convulsion is a rare presentation for acute hemolysis due to Glucose-6-Phosphate Dehydrogenase deficiency. Herein, we report a case report of a Glucose-6-Phosphate Dehydrogenase deficiency diagnosed patient after presentation with convulsion. A 70 year-old woman patient had been hospitalized because of convulsion and fatigue. She has not had similar symptoms before. She had ingested fava beans in the last two days. Her hypophyseal and brain magnetic resonance imaging were normal. Blood transfusion was performed and the patient recovered.

Metabolic and hormonal responses of growing modern meat type chickens to fasting

USDA-ARS?s Scientific Manuscript database

The present study compared the effects of fasting on circulating concentrations of glucose, insulin and glucagon in male and female modern meat-type chickens (Ross 708) at three ages (19 d, 33 d and 47 d). Plasma concentrations of glucose were reduced by fasting with reductions of 24.9% (19-d-old),...

Suspected hypoglycaemia in out patient practice: accuracy of dried blood spot analysis.

PubMed

Parker, D R; Bargiota, A; Cowan, F J; Corrall, R J

1997-12-01

The assay of dried blood spots on filter paper to determine blood glucose concentration has been used to detect hypoglycaemia in out patients. We assessed the accuracy of this approach in assaying blood glucose concentrations in the hypoglycaemic range. Volunteers were rendered hypoglycaemic by intravenous infusion of insulin. The glucose concentration in simultaneously taken blood samples was measured either fresh or after drying on filter paper. Twenty-four healthy young volunteers and 9 patients with insulin-dependent diabetes were studied. Plasma glucose concentrations were measured using a standard auto analyser glucose oxidase method. Whole blood taken simultaneously was placed on prepared filter paper and allowed to dry; glucose concentration was then measured using a well-established technique. A correction factor was applied to convert the glucose concentration of plasma to that of whole blood. The relationship between glucose concentrations measured by the two methods was determined by regression coefficient. In the unequivocally hypoglycaemic range (plasma < or = 2.5 mmol/l), corrected dried blood spot glucose concentrations significantly correlated with standard plasma glucose concentrations (r = 0.81; P < 0.001). The dried blood spot method had a sensitivity of 91%. In the range designated probable hypoglycaemia (plasma < or = 3.3 mmol/l), there was also significant correlation (r = 0.90; P < 0.001) and the sensitivity was 96%. The specificity of the dried blood spot method was 100% in both ranges. Measurement of glucose concentrations in dried blood spots is specific and sensitive in the hypoglycaemic range. The present study indicates that hypoglycaemia may be excluded or confirmed respectively when levels in excess of 3.7 or below 2.8 mmol/l are found in uncorrected dried blood spot analysis.

Diffusion of D-glucose measured in the cytosol of a single astrocyte.

PubMed

Kreft, Marko; Lukšič, Miha; Zorec, Tomaž M; Prebil, Mateja; Zorec, Robert

2013-04-01

Astrocytes interact with neurons and endothelial cells and may mediate exchange of metabolites between capillaries and nerve terminals. In the present study, we investigated intracellular glucose diffusion in purified astrocytes after local glucose uptake. We used a fluorescence resonance energy transfer (FRET)-based nano sensor to monitor the time dependence of the intracellular glucose concentration at specific positions within the cell. We observed a delay in onset and kinetics in regions away from the glucose uptake compared with the region where we locally super-fused astrocytes with the D-glucose-rich solution. We propose a mathematical model of glucose diffusion in astrocytes. The analysis showed that after gradual uptake of glucose, the locally increased intracellular glucose concentration is rapidly spread throughout the cytosol with an apparent diffusion coefficient (D app) of (2.38 ± 0.41) × 10(-10) m(2) s(-1) (at 22-24 °C). Considering that the diffusion coefficient of D-glucose in water is D = 6.7 × 10(-10) m(2) s(-1) (at 24 °C), D app determined in astrocytes indicates that the cytosolic tortuosity, which hinders glucose molecules, is approximately three times higher than in aqueous solution. We conclude that the value of D app for glucose measured in purified rat astrocytes is consistent with the view that cytosolic diffusion may allow glucose and glucose metabolites to traverse from the endothelial cells at the blood-brain barrier to neurons and neighboring astrocytes.

Corticosterone alters materno-fetal glucose partitioning and insulin signalling in pregnant mice

PubMed Central

Vaughan, O R; Fisher, H M; Dionelis, K N; Jefferies, E C; Higgins, J S; Musial, B; Sferruzzi-Perri, A N; Fowden, A L

2015-01-01

Glucocorticoids affect glucose metabolism in adults and fetuses, although their effects on materno-fetal glucose partitioning remain unknown. The present study measured maternal hepatic glucose handling and placental glucose transport together with insulin signalling in these tissues in mice drinking corticosterone either from day (D) 11 to D16 or D14 to D19 of pregnancy (term = D21). On the final day of administration, corticosterone-treated mice were hyperinsulinaemic (P < 0.05) but normoglycaemic compared to untreated controls. In maternal liver, there was no change in glycogen content or glucose 6-phosphatase activity but increased Slc2a2 glucose transporter expression in corticosterone-treated mice, on D16 only (P < 0.05). On D19, but not D16, transplacental 3H-methyl-d-glucose clearance was reduced by 33% in corticosterone-treated dams (P < 0.05). However, when corticosterone-treated animals were pair-fed to control intake, aiming to prevent the corticosterone-induced increase in food consumption, 3H-methyl-d-glucose clearance was similar to the controls. Depending upon gestational age, corticosterone treatment increased phosphorylation of the insulin-signalling proteins, protein kinase B (Akt) and glycogen synthase-kinase 3β, in maternal liver (P < 0.05) but not placenta (P > 0.05). Insulin receptor and insulin-like growth factor type I receptor abundance did not differ with treatment in either tissue. Corticosterone upregulated the stress-inducible mechanistic target of rapamycin (mTOR) suppressor, Redd1, in liver (D16 and D19) and placenta (D19), in ad libitum fed animals (P < 0.05). Concomitantly, hepatic protein content and placental weight were reduced on D19 (P < 0.05), in association with altered abundance and/or phosphorylation of signalling proteins downstream of mTOR. Taken together, the data indicate that maternal glucocorticoid excess reduces fetal growth partially by altering placental glucose transport and mTOR signalling. Key points Glucocorticoids regulate fetal and adult glucose metabolism, in part by influencing the actions of insulin. However, their effects on materno-fetal glucose partitioning remain largely unknown. In the present study, when pregnant mice were given the natural glucocorticoid, corticosterone, plasma insulin concentrations and liver insulin-signalling increased but the blood glucose concentration remained normal. However, in the placenta, glucose transport was reduced in association with the lower activity of some insulin signalling proteins, depending on the day of pregnancy and maternal food intake. In both liver and placenta, there was increased expression of the Redd1 (Ddit4) gene when the plasma corticosterone concentration was raised. The results show that maternal glucocorticoids interact with signalling pathways in the placenta to limit materno-fetal glucose partitioning. PMID:25625347

Fever is not responsible for the elevated glucose kinetics in sepsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lang, C.H.; Bagby, G.J.; Blakesley, H.L.

Previous studies have suggested that alterations in the classical neuroendocrine system may not be responsible for the increased glucose metabolism observed during hypermetabolic sepsis. The purpose of the present study was to determine whether inhibition of the cyclooxygenase pathway with indomethacin, which prevents the production of arachidonic acid metabolites by this pathway and the sepsis-induced increase in body temperature, would abolish the increases in glucose appearance (Ra), recycling, and hyperlactacidemia. Sepsis was induced in chronically catheterized conscious rats by multiple injections of live Escherichia coli via a subcutaneous catheter. Septic animals received iv injections of indomethacin every 6-8 hr tomore » block the cyclooxygenase pathway. Glucose kinetics were assessed in 24-hr fasted rats using a constant iv infusion of (6-/sup 3/H)- and (U-/sup 14/C) glucose. Treatment with indomethacin prevented the 1-2/sup 0/C increase in body temperature observed in septic animals. Septic rats exhibited an elevated plasma lactate concentration and increased rates of glucose appearance and recycling. The sepsis-induced alterations in these variables were not attenuated by indomethacin. These results suggest that neither elevated body temperature nor the generation of arachidonic acid metabolites of the cyclooxygenase pathway is responsible for increasing glucose production in hypermetabolic septic rats.« less

Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome.

PubMed

Yilmaz, Murat; Bukan, Neslihan; Ersoy, Reyhan; Karakoç, Ayhan; Yetkin, Ilhan; Ayvaz, Göksun; Cakir, Nuri; Arslan, Metin

2005-09-01

The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.

Stable isotope probing reveals the importance of Comamonas and Pseudomonadaceae in RDX degradation in samples from a Navy detonation site.

PubMed

Jayamani, Indumathy; Cupples, Alison M

2015-07-01

This study investigated the microorganisms involved in hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) degradation from a detonation area at a Navy base. Using Illumina sequencing, microbial communities were compared between the initial sample, samples following RDX degradation, and controls not amended with RDX to determine which phylotypes increased in abundance following RDX degradation. The effect of glucose on these communities was also examined. In addition, stable isotope probing (SIP) using labeled ((13)C3, (15)N3-ring) RDX was performed. Illumina sequencing revealed that several phylotypes were more abundant following RDX degradation compared to the initial soil and the no-RDX controls. For the glucose-amended samples, this trend was strong for an unclassified Pseudomonadaceae phylotype and for Comamonas. Without glucose, Acinetobacter exhibited the greatest increase following RDX degradation compared to the initial soil and no-RDX controls. Rhodococcus, a known RDX degrader, also increased in abundance following RDX degradation. For the SIP study, unclassified Pseudomonadaceae was the most abundant phylotype in the heavy fractions in both the presence and absence of glucose. In the glucose-amended heavy fractions, the 16S ribosomal RNA (rRNA) genes of Comamonas and Anaeromxyobacter were also present. Without glucose, the heavy fractions also contained the 16S rRNA genes of Azohydromonas and Rhodococcus. However, all four phylotypes were present at a much lower level compared to unclassified Pseudomonadaceae. Overall, these data indicate that unclassified Pseudomonadaceae was primarily responsible for label uptake in both treatments. This study indicates, for the first time, the importance of Comamonas for RDX removal.

The metabolic impact of β-hydroxybutyrate on neurotransmission: Reduced glycolysis mediates changes in calcium responses and KATP channel receptor sensitivity.

PubMed

Lund, Trine M; Ploug, Kenneth B; Iversen, Anne; Jensen, Anders A; Jansen-Olesen, Inger

2015-03-01

Glucose is the main energy substrate for neurons, and ketone bodies are known to be alternative substrates. However, the capacity of ketone bodies to support different neuronal functions is still unknown. Thus, a change in energy substrate from glucose alone to a combination of glucose and β-hydroxybutyrate might change neuronal function as there is a known coupling between metabolism and neurotransmission. The purpose of this study was to shed light on the effects of the ketone body β-hydroxybutyrate on glycolysis and neurotransmission in cultured murine glutamatergic neurons. Previous studies have shown an effect of β-hydroxybutyrate on glucose metabolism, and the present study further specified this by showing attenuation of glycolysis when β-hydroxybutyrate was present in these neurons. In addition, the NMDA receptor-induced calcium responses in the neurons were diminished in the presence of β-hydroxybutyrate, whereas a direct effect of the ketone body on transmitter release was absent. However, the presence of β-hydroxybutyrate augmented transmitter release induced by the KATP channel blocker glibenclamide, thus giving an indirect indication of the involvement of KATP channels in the effects of ketone bodies on transmitter release. Energy metabolism and neurotransmission are linked and involve ATP-sensitive potassium (KATP ) channels. However, it is still unclear how and to what degree available energy substrate affects this link. We investigated the effect of changing energy substrate from only glucose to a combination of glucose and R-β-hydroxybutyrate in cultured neurons. Using the latter combination, glycolysis was diminished, NMDA receptor-induced calcium responses were lower, and the KATP channel blocker glibenclamide caused a higher transmitter release. © 2014 International Society for Neurochemistry.

Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au; De Souza, David P.; Burch, Micah L.

Rationale: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). Methods and results: In vivo muscle glucose andmore » intermediary metabolism was investigated following oral administration of [U-{sup 13}C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography–mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. Conclusions: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle. - Highlights: • Dynamic metabolomics was used to investigate muscle glucose metabolism in vivo. • Mitochondrial TCA cycle metabolism is altered in muscle of HFD mice. • This defect was not pyruvate dehydrogenase mediated, as has been previously thought. • Mitochondrial TCA cycle anaplerosis in muscle is virtually absent during the OGTT.« less

Determinants of hemoglobin A1c level in patients with type 2 diabetes after in-hospital diabetes education: A study based on continuous glucose monitoring.

PubMed

Torimoto, Keiichi; Okada, Yosuke; Sugino, Sachiko; Tanaka, Yoshiya

2017-05-01

We investigated the relationship between blood glucose profile at hospital discharge, evaluated by continuous glucose monitoring (CGM), and hemoglobin A1c (HbA1c) level at 12 weeks after discharge in patients with type 2 diabetes who received inpatient diabetes education. This was a retrospective study. The participants were 54 patients with type 2 diabetes who did not change their medication after discharge. The mean blood glucose (MBG), standard deviation, coefficient of variation, mean postprandial glucose excursion, maximum blood glucose, minimum blood glucose, percentage of time with blood glucose at ≥180 mg/dL (time at ≥180), percentage of time with blood glucose at ≥140 mg/dL, and percentage of time with blood glucose at <70 mg/dL were measured at admission and discharge using CGM. The primary end-point was the relationship between CGM parameters and HbA1c level at 12 weeks after discharge. The HbA1c level at 12 weeks after discharge correlated with MBG level (r = 0.30, P = 0.029). Multivariate analysis showed that MBG level and disease duration were predictors of 12-week HbA1c level. Multivariate logistic regression analysis was carried out considering goal achievement as a HbA1c level <7.0% 12 weeks after discharge. Disease duration and time at ≥180 were associated with goal achievement. The present results suggested that blood glucose profile at discharge using CGM seems useful to predict HbA1c level after discharge in patients with type 2 diabetes who received inpatient diabetes education. Early treatment to improve MBG level, as well as postprandial hyperglycemia, is important to achieve strict glycemic control. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Evidence for the absence of cerebral glucose-6-phosphatase activity in glycogen storage disease type I (Von Gierke's disease)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, M.E.; Mazziotta, J.C.; Hawkins, R.A.

1981-01-01

Glycogen storage disease type I (GSD-I) is characterized by a functional deficit in glucose-6-phosphatase that normally hydrolyzes glucose-6-PO/sub 4/ to glucose. This enzyme is primarily found in liver, kidney, and muscle but it is also present in brain, where it appears to participate in the regulation of cerebral tissue glucose. Since most neurological symptoms in GSD-I patients involve systemic hypoglycemia, previous reports have not examined possible deficiencies in phosphatase activity in the brain. Positron computed tomography, F-18-labeled 2-fluorodeoxyglucose (FDG) and a tracer kinetic model for FDG were used to measure the cortical plasma/tissue forward and reverse transport, phosphorylation and dephosphorylationmore » rate constants, tissue/plasma concentration gradient, tissue concentration turnover rate for this competitive analog of glucose, and the cortical metabolic rates for glucose. Studies were carried out in age-matched normals (N = 13) and a single GSD-I patient. The dephosphorylation rate constant in the GSD-I patient was about one tenth the normal value indicating a low level of cerebral phosphatase activity. The other measured parameters were within normal limits except for the rate of glucose phosphorylation which reflected a cortical glucose metabolic rate one half the normal value. Since glucose transport and tissue glucose concentration was normal, the reduced cortical glucose metabolism probably results from the use of alternative substrates (..beta..-hydroxybutyrate and acetoacetate) which are consistently elevated in the plasma of GSD-I patients.« less

Influence of low glucose supply on the regulation of gene expression by nucleus pulposus cells and their responsiveness to mechanical loading.

PubMed

Rinkler, Christina; Heuer, Frank; Pedro, Maria Teresa; Mauer, Uwe Max; Ignatius, Anita; Neidlinger-Wilke, Cornelia

2010-10-01

Environmental alterations resulting in a decrease in the nutrient supply have been associated with intervertebral disc (IVD) degeneration, particularly of the nucleus pulposus (NP). The goal of the present study was to examine the hypothesis that glucose deprivation alters the metabolism of NP cells and their responsiveness to mechanical loading. A possible interaction of glucose supply and hydrostatic pressure (HP) with gene expression by NP cells has not been investigated. The influence of glucose supply (physiological concentration: 5 mM, reduction: 0 or 0.5 mM) and cyclic HP loading (2.5 MPa, 0.1 Hz, 30 minutes) on bovine and human NP cell matrix turnover was analyzed by quantitative real-time reverse transcriptase–polymerase chain reaction. Glucose-dependent effects on cell viability were determined by trypan blue exclusion. A glycosaminoglycan (GAG) assay was performed to determine nutritional effects on the protein level. Glucose reduction resulted in significant downregulations (p < 0.05) of aggrecan, collagen-I, and collagen-II gene expression by bovine NP cells. Exemplary human donors also displayed a similar trend for aggrecan and collagen-II, whereas matrix metalloproteinases (MMPs) tended to be upregulated under glucose deprivation. After HP loading, human NP cells showed individual upregulations of collagen-I and collagen-II expression, while MMP expression tended to be downregulated under glucose reduction relative to a normal glucose supply. Cell viability decreased with glucose deprivation. The GAG content was similar in all groups at Day 1, whereas at Day 3 there was a significant increase under physiological conditions. Glucose deprivation strongly affected NP cell metabolism. The effects of an altered glucose supply on gene expression were more pronounced than the mechanically induced effects. Data in this study demonstrate that the glucose environment is more critical for disc cell metabolism than mechanical loads. In individual human donors, however, adequate mechanical stimuli might have a beneficial effect on matrix turnover during IVD degeneration.

Saccharomyces cerevisiae and metabolic activators: HXT3 gene expression and fructose/glucose discrepancy in sluggish fermentation conditions.

PubMed

Díaz-Hellín, Patricia; Naranjo, Victoria; Úbeda, Juan; Briones, Ana

2016-12-01

When exposed to mixtures of glucose and fructose, as occurs during the fermentation of grape juice into wine, Saccharomyces cerevisiae uses these sugars at different rates. Moreover, glucose and fructose are transported by the same hexose transporters (HXT), which present a greater affinity for glucose, so that late in fermentation, fructose becomes the predominant sugar. Only a few commercial fermentation activators are available to optimally solve the problems this entails. The aim of this study was to investigate the relation between HXT3 gene expression and fructose/glucose discrepancy in two different media inoculated with a commercial wine strain of S. cerevisiae in the presence of three metabolic activators. Fermentation kinetics, vitality and major metabolites were also measured. Rehydration with ergosterol improved the area under the curve and the growth rate (µ max ) in both studied media. Also, the fructose/glucose discrepancy values were improved with all activator treatments, highlighting rehydration in the presence of ascorbic acid. The yeast rehydration process was demonstrated to influence HXT3 expression under the studied conditions. Tetrahydrofolic acid treatment greatly influenced HXT3 gene expression, especially on the 12th day of the fermentation process. To a lesser extent, ergosterol and ascorbic acid also improved this parameter.

Type 2 diabetes mellitus and impaired glucose regulation in overweight and obese children and adolescents living in Serbia.

PubMed

Vukovic, R; Mitrovic, K; Milenkovic, T; Todorovic, S; Zdravkovic, D

2012-11-01

An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.2-18.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n=1) and impaired glucose regulation in 15.9% (n=48) of the subjects. Isolated IFG was detected in 4.3% (n=13), isolated IGT in 8.3% (n=25) and combined IFG and IGT in 3.3% (n=10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity.

In Vitro Study on Glucose Utilization Capacity of Bioactive Fractions of Houttuynia cordata in Isolated Rat Hemidiaphragm and Its Major Phytoconstituent

PubMed Central

Kumar, Manish; Prasad, Satyendra K.; Hemalatha, Siva

2016-01-01

Objective. The whole plant of Houttuynia cordata has been reported to have potent antihyperglycemic activity. Therefore, the present study was undertaken to investigate the glucose utilization capacity of bioactive fractions of ethanol extract of Houttuynia cordata (HC) in isolated rat hemidiaphragm. Methods. All the fractions, that is, aqueous (AQ), hexane (HEX), chloroform (CHL), and ethyl acetate (EA), obtained from ethanol extract of H. cordata were subjected to phytochemical standardization use in quercetin as a marker with the help of HPTLC. Further, glucose utilization capacity by rat hemidiaphragm was evaluated in 12 different sets of in vitro experiments. In the study, different fractions from H. cordata as mentioned above were evaluated, where insulin was used as standard and quercetin as a biological standard. Results. Among all the tested fractions, AQ and EA significantly increased glucose uptake by isolated rat hemidiaphragm compared to negative control. Moreover, AQ fractions enhanced the uptake of glucose significantly (p < 0.05) and was found to be more effective than insulin. Conclusions. The augmentation in glucose uptake by hemidiaphragm in presence of AQ and EA fractions may be attributed to the presence of quercetin, which was found to be 7.1 and 3.2% w/w, respectively, in both the fractions. PMID:26925100

In Vitro Study on Glucose Utilization Capacity of Bioactive Fractions of Houttuynia cordata in Isolated Rat Hemidiaphragm and Its Major Phytoconstituent.

PubMed

Kumar, Manish; Prasad, Satyendra K; Hemalatha, Siva

2016-01-01

Objective. The whole plant of Houttuynia cordata has been reported to have potent antihyperglycemic activity. Therefore, the present study was undertaken to investigate the glucose utilization capacity of bioactive fractions of ethanol extract of Houttuynia cordata (HC) in isolated rat hemidiaphragm. Methods. All the fractions, that is, aqueous (AQ), hexane (HEX), chloroform (CHL), and ethyl acetate (EA), obtained from ethanol extract of H. cordata were subjected to phytochemical standardization use in quercetin as a marker with the help of HPTLC. Further, glucose utilization capacity by rat hemidiaphragm was evaluated in 12 different sets of in vitro experiments. In the study, different fractions from H. cordata as mentioned above were evaluated, where insulin was used as standard and quercetin as a biological standard. Results. Among all the tested fractions, AQ and EA significantly increased glucose uptake by isolated rat hemidiaphragm compared to negative control. Moreover, AQ fractions enhanced the uptake of glucose significantly (p < 0.05) and was found to be more effective than insulin. Conclusions. The augmentation in glucose uptake by hemidiaphragm in presence of AQ and EA fractions may be attributed to the presence of quercetin, which was found to be 7.1 and 3.2% w/w, respectively, in both the fractions.

Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

NASA Astrophysics Data System (ADS)

Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

2016-03-01

Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

Ghrelin administered spinally increases the blood glucose level in mice.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-04-01

Ghrelin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of ghrelin located in the spinal cord in the regulation of the blood glucose level were investigated in ICR mice. We found that intrathecal (i.t.) injection with ghrelin (from 1 to 10 μg) caused an elevation of the blood glucose level. In addition, i.t. pretreatment with YIL781 (ghrelin receptor antagonist; from 0.1 to 5 μg) markedly attenuated ghrelin-induced hyperglycemic effect. The plasma insulin level was increased by ghrelin. The enhanced plasma insulin level by ghrelin was reduced by i.t. pretreatment with YIL781. However, i.t. pretreatment with glucagon-like peptide-1 (GLP-1; 5 μg) did not affect the ghrelin-induced hyperglycemia. Furthermore, i.t. administration with ghrelin also elevated the blood glucose level, but in an additive manner, in d-glucose-fed model. Our results suggest that the activation of ghrelin receptors located in the spinal cord plays important roles for the elevation of the blood glucose level. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to 2,4-dichlorophenoxyacetic acid induced PPARβ-dependent disruption of glucose metabolism in HepG2 cells.

PubMed

Sun, Haidong; Shao, Wentao; Liu, Hui; Jiang, Zhaoyan

2018-04-09

2,4-Dichlorophenoxyacetic acid is one of the most widely used herbicides. Its impact on health is increasingly attracting great attentions. This study aimed to investigate the effect of 2,4-dichlorophenoxyacetic acid on glucose metabolism in HepG2 cells and the underlying mechanism. After 24 h exposure to 2,4-dichlorophenoxyacetic acid, glycogen was measured by PAS staining and glucose by ELISA in HepG2 cells. The expression of genes involved in glucose metabolism was measured by real-time PCR, Western blotting, and immunofluorescence. HepG2 cells presented more extracellular glucose consumption and glycogen content after exposed to 2,4-dichlorophenoxyacetic acid. Expression of gluconeogenesis-related genes, FoxO1, and CREB is significantly elevated. Moreover, PPARβ was up-regulated dose-dependently. SiRNA knockdown of PPARβ completely rescued the increase of glycogen accumulation and glucose uptake, and the up-regulation of FOXO1 and CREB expression. Our findings propose novel mechanisms that 2,4-dichlorophenoxyacetic acid causes glucose metabolism dysfunction through PPARβ in HepG2 cells.

Ability of higenamine and related compounds to enhance glucose uptake in L6 cells.

PubMed

Kato, Eisuke; Kimura, Shunsuke; Kawabata, Jun

2017-12-15

β2-Adrenergic receptor (β2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has β2AR agonist activity, but the involvement of each functional groups in β2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through β2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 4'-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer. Copyright © 2017 Elsevier Ltd. All rights reserved.

A systematic review and meta-analyses of nonsucrose sweet solutions for pain relief in neonates.

PubMed

Bueno, Mariana; Yamada, Janet; Harrison, Denise; Khan, Sobia; Ohlsson, Arne; Adams-Webber, Thomasin; Beyene, Joseph; Stevens, Bonnie

2013-01-01

Sucrose has been demonstrated to provide analgesia for minor painful procedures in infants. However, results of trials investigating other sweet solutions for neonatal pain relief have not yet been synthesized. To establish the efficacy of nonsucrose sweet-tasting solutions for pain relief during painful procedures in neonates. The present article is a systematic review and meta-analyses of the literature. Standard methods of the Cochrane Neonatal Collaborative Review Group were used. Literature searches were reviewed for randomized controlled trials investigating the use of sweet solutions, except sucrose, for procedural pain management in neonates. Outcomes assessed included validated pain measures and behavioural and physiological indicators. Thirty-eight studies (3785 neonates) were included, 35 of which investigated glucose. Heel lancing was performed in 21⁄38 studies and venipuncture in 11⁄38 studies. A 3.6-point reduction in Premature Infant Pain Profile scores during heel lances was observed in studies comparing 20% to 30% glucose with no intervention (two studies, 124 neonates; mean difference -3.6 [95% CI -4.6 to -2.6]; P<0.001; I2=54%). A significant reduction in the incidence of cry after venipuncture for infants receiving 25% to 30% glucose versus water or no intervention was observed (three studies, 130 infants; risk difference -0.18 [95% CI -0.31 to -0.05]; P=0.008, number needed to treat = 6 [95% CI 3 to 20]; I2=63%). The present systematic review and meta-analyses demonstrate that glucose reduces pain scores and crying during single heel lances and venipunctures. Results indicate that 20% to 30% glucose solutions have analgesic effects and can be recommended as an alternative to sucrose for procedural pain reduction in healthy term and preterm neonates.

Design, development, and evaluation of a novel microneedle array-based continuous glucose monitor.

PubMed

Jina, Arvind; Tierney, Michael J; Tamada, Janet A; McGill, Scott; Desai, Shashi; Chua, Beelee; Chang, Anna; Christiansen, Mark

2014-05-01

The development of accurate, minimally invasive continuous glucose monitoring (CGM) devices has been the subject of much work by several groups, as it is believed that a less invasive and more user-friendly device will result in greater adoption of CGM by persons with insulin-dependent diabetes. This article presents the results of preliminary clinical studies in subjects with diabetes of a novel prototype microneedle-based continuous glucose monitor. In this device, an array of tiny hollow microneedles is applied into the epidermis from where glucose in interstitial fluid (ISF) is transported via passive diffusion to an amperometric glucose sensor external to the body. Comparison of 1396 paired device glucose measurements and fingerstick blood glucose readings for up to 72-hour wear in 10 diabetic subjects shows the device to be accurate and well tolerated by the subjects. Overall mean absolute relative difference (MARD) is 15% with 98.4% of paired points in the A+B region of the Clarke error grid. The prototype device has demonstrated clinically accurate glucose readings over 72 hours, the first time a microneedle-based device has achieved such performance. © 2014 Diabetes Technology Society.

A CuNi/C Nanosheet Array Based on a Metal-Organic Framework Derivate as a Supersensitive Non-Enzymatic Glucose Sensor

NASA Astrophysics Data System (ADS)

Zhang, Li; Ye, Chen; Li, Xu; Ding, Yaru; Liang, Hongbo; Zhao, Guangyu; Wang, Yan

2018-06-01

Bimetal catalysts are good alternatives for non-enzymatic glucose sensors owing to their low cost, high activity, good conductivity, and ease of fabrication. In the present study, a self-supported CuNi/C electrode prepared by electrodepositing Cu nanoparticles on a Ni-based metal-organic framework (MOF) derivate was used as a non-enzymatic glucose sensor. The porous construction and carbon scaffold inherited from the Ni-MOF guarantee good kinetics of the electrode process in electrochemical glucose detection. Furthermore, Cu nanoparticles disturb the array structure of MOF derived films and evidently enhance their electrochemical performances in glucose detection. Electrochemical measurements indicate that the CuNi/C electrode possesses a high sensitivity of 17.12 mA mM-1 cm-2, a low detection limit of 66.67 nM, and a wider linearity range from 0.20 to 2.72 mM. Additionally, the electrode exhibits good reusability, reproducibility, and stability, thereby catering to the practical use of glucose sensors. Similar values of glucose concentrations in human blood serum samples are detected with our electrode and with the method involving glucose-6-phosphate dehydrogenase; the results further demonstrate the practical feasibility of our electrode.

Approach to Assessing Determinants of Glucose Homeostasis in the Conscious Mouse

PubMed Central

Hughey, Curtis C.; Wasserman, David H.; Lee-Young, Robert S.; Lantier, Louise

2014-01-01

Obesity and type 2 diabetes lessen the quality of life of those afflicted and place considerable burden on the healthcare system. Furthermore, the detrimental impact of these pathologies is expected to persist or even worsen. Diabetes is characterized by impaired insulin action and glucose homeostasis. This has led to a rapid increase in the number of mouse models of metabolic disease being used in the basic sciences to assist in facilitating a greater understanding of the metabolic dysregulation associated with obesity and diabetes, the identification of therapeutic targets, and the discovery of effective treatments. This review briefly describes the most frequently utilized models of metabolic disease. A presentation of standard methods and technologies on the horizon for assessing metabolic phenotypes in mice, with particular emphasis on glucose handling and energy balance, is provided. The article also addresses issues related to study design, selection and execution of metabolic tests of glucose metabolism, the presentation of data, and interpretation of results. PMID:25074441

The effect of an instant hand sanitizer on blood glucose monitoring results.

PubMed

Mahoney, John J; Ellison, John M; Glaeser, Danielle; Price, David

2011-11-01

People with diabetes mellitus are instructed to clean their skin prior to self-monitoring of blood glucose to remove any dirt or food residue that might affect the reading. Alcohol-based hand sanitizers have become popular when soap and water are not available. The aim of this study was to determine whether a hand sanitizer is compatible with glucose meter testing and effective for the removal of exogenous glucose. We enrolled 34 nonfasting subjects [14 male/20 female, mean ages 45 (standard deviation, 9.4)] years, 2 with diagnosed diabetes/32 without known diabetes]. Laboratory personnel prepared four separate fingers on one hand of each subject by (1) cleaning the second finger with soap and water and towel drying (i.e., control finger), (2) cleaning the third finger with an alcohol-based hand sanitizer, (3) coating the fourth finger with cola and allowing it to air dry, and (4) coating the fifth finger with cola and then cleaning it with the instant hand sanitizer after the cola had dried. Finger sticks were performed on each prepared finger and blood glucose was measured. Several in vitro studies were also performed to investigate the effectiveness of the hand sanitizer for removal of exogenous glucose.z Mean blood glucose values from fingers cleaned with instant hand sanitizer did not differ significantly from the control finger (p = .07 and .08, respectively) and resulted in 100% accurate results. Blood glucose data from the fourth (cola-coated) finger were substantially higher on average compared with the other finger conditions, but glucose data from the fifth finger (cola-coated then cleaned with hand sanitizer) was similar to the control finger. The data from in vitro experiments showed that the hand sanitizer did not adversely affect glucose meter results, but when an exogenous glucose interference was present, the effectiveness of the hand sanitizer on glucose bias (range: 6% to 212%) depended on the surface area and degree of dilution. In our study, use of an instant hand sanitizer was compatible with the results of a blood glucose monitor and did not affect finger stick blood glucose results. However, depending on surface area, hand sanitizers may not be adequate for cleaning the skin prior to glucose meter testing. © 2011 Diabetes Technology Society.

The Effect of an Instant Hand Sanitizer on Blood Glucose Monitoring Results

PubMed Central

Mahoney, John J; Ellison, John M; Glaeser, Danielle; Price, David

2011-01-01

Background People with diabetes mellitus are instructed to clean their skin prior to self-monitoring of blood glucose to remove any dirt or food residue that might affect the reading. Alcohol-based hand sanitizers have become popular when soap and water are not available. The aim of this study was to determine whether a hand sanitizer is compatible with glucose meter testing and effective for the removal of exogenous glucose. Methods We enrolled 34 nonfasting subjects [14 male/20 female, mean ages 45 (standard deviation, 9.4)] years, 2 with diagnosed diabetes/32 without known diabetes]. Laboratory personnel prepared four separate fingers on one hand of each subject by (1) cleaning the second finger with soap and water and towel drying (i.e., control finger), (2) cleaning the third finger with an alcohol-based hand sanitizer, (3) coating the fourth finger with cola and allowing it to air dry, and (4) coating the fifth finger with cola and then cleaning it with the instant hand sanitizer after the cola had dried. Finger sticks were performed on each prepared finger and blood glucose was measured. Several in vitro studies were also performed to investigate the effectiveness of the hand sanitizer for removal of exogenous glucose.z Results Mean blood glucose values from fingers cleaned with instant hand sanitizer did not differ significantly from the control finger (p = .07 and .08, respectively) and resulted in 100% accurate results. Blood glucose data from the fourth (cola-coated) finger were substantially higher on average compared with the other finger conditions, but glucose data from the fifth finger (cola-coated then cleaned with hand sanitizer) was similar to the control finger. The data from in vitro experiments showed that the hand sanitizer did not adversely affect glucose meter results, but when an exogenous glucose interference was present, the effectiveness of the hand sanitizer on glucose bias (range: 6% to 212%) depended on the surface area and degree of dilution. Conclusions In our study, use of an instant hand sanitizer was compatible with the results of a blood glucose monitor and did not affect finger stick blood glucose results. However, depending on surface area, hand sanitizers may not be adequate for cleaning the skin prior to glucose meter testing. PMID:22226262

Immediate effect of passive static stretching versus resistance exercises on postprandial blood sugar levels in type 2 diabetes mellitus: a randomized clinical trial.

PubMed

Gurudut, Peeyoosha; Rajan, Abey P

2017-10-01

The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. In India, more than 61.3 million people have been presently diagnosed with type 2 diabetes mellitus. It is possible to control the circulating blood glucose levels by reducing life style risk factors through physical activities comprising of muscle stretches, aerobic training, resistance exercises (REs), yoga, etc. The aim of this study is to identify and compare the immediate effect of passive static stretching (PSS) versus RE on blood glucose level in individuals with type 2 diabetes mellitus. The present study included 51 participants between the age of 40-65 years with type 2 diabetes mellitus, to study the immediate effect of 60-min PSS (n=25) and 60-min RE (n=26). The outcome measure was blood glucose level which was checked by glucometer (free-style neo). Blood sugar was assessed at 3 points of time that included fasting blood sugar level, 2 hr after the meal and immediately after the exercise regimen. Results of this study showed significant reduction in blood glucose level in subjects according to glucometer with PSS ( P =0.000) and RE ( P =0.00). However, both groups demonstrated equal effect in terms of lowering blood sugar level immediately after the exercise. The conclusion is both PSS and RE are effective in reducing postprandial blood glucose level in type 2 diabetes mellitus and must be prescribed for the patients who demonstrate difficulty in controlling post prandial spike.

Changes in blood glucose and salivary cortisol are not necessary for arousal to enhance memory in young or older adults.

PubMed

Gore, Jane B; Krebs, Desiree L; Parent, Marise B

2006-06-01

Emotional arousal enhances memory, and this memory-enhancing effect may involve neurochemicals released by arousal, such as glucose and cortisol. Physiological consequences of arousal change with age, and these changes may contribute to age-related memory decline. The present study examined whether emotionally arousing pictures would affect glucose and cortisol levels and enhance memory in young and older adults. Blood glucose and salivary cortisol were measured once before and six times after young and old adults viewed either 60 highly arousing or 60 relatively neutral pictures. Recall for the stimuli was measured 75 min later. The results indicated that recall was impaired in older adults. Arousal as measured by self-report enhanced recall in both young and older adults. However, arousal did not affect glucose or cortisol levels in either group. These findings demonstrate that changes in blood glucose or salivary cortisol levels are not necessary for arousal to enhance memory.

How to Design a Biosensor

PubMed Central

Ward, W. Kenneth

2007-01-01

Amperometric sensors for continuous glucose monitoring could prevent acute and chronic complications of diabetes, but research is needed to improve accuracy and stability. In designing sensors, interference from non-glucose analytes can be minimized by use of filtration membranes or electron transfer mediators that allow polarization at low potentials. If oxygen is required for the enzymatic reaction with glucose, then the outer permselective membrane must have substantial oxygen permeability. For this reason, during development of permselective membranes, permeability studies (such as performed by Tipnis and colleagues in this issue) can be used to measure transport of glucose and oxygen and optimize membrane structure. Tipnis and colleagues present a novel biosensor based with separate layers for glucose-oxygen permselectivity, enzymatic conversion, and avoidance of interference. They also address sensor stability, in part by comparing sensor function during ascending vs descending glucose levels. By measuring the difference, they were able to minimize this aspect of instability (hysterisis), which assisted them in selecting a promising permselective membrane based on iron and humic acid. PMID:19888407

Glucose biosensor based on immobilization of glucose oxidase on a carbon paste electrode modified with microsphere-attached l-glycine.

PubMed

Donmez, Soner; Arslan, Fatma; Sarı, Nurşen; Hasanoğlu Özkan, Elvan; Arslan, Halit

2017-09-01

In the present study, a novel biosensor that is sensitive to glucose was prepared using the microspheres modified with (4-formyl-3-methoxyphenoxymethyl)polystyrene (FMPS) with l-glycine. Polymeric microspheres having Schiff bases were prepared from FMPS using the glycine condensation method. Glucose oxidase enzyme was immobilized onto modified carbon paste electrode by cross-linking with glutaraldehyde. Oxidation of enzymatically produced H 2 O 2 (+0.5 V vs. Ag/AgCl) was used for determination of glucose. Optimal temperature and pH were found as 50 °C and 8.0, respectively. The glucose biosensor showed a linear working range from 5.0 × 10 -4 to 1.0 × 10 -2 M, R 2 = 0.999. Storage and operational stability of the biosensor were also investigated. The biosensor gave perfect reproducible results after 20 measurements with 3.3% relative standard deviation. It also had good storage stability. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Insulin-coated gold nanoparticles as a new concept for personalized and adjustable glucose regulation.

PubMed

Shilo, Malka; Berenstein, Peter; Dreifuss, Tamar; Nash, Yuval; Goldsmith, Guy; Kazimirsky, Gila; Motiei, Menachem; Frenkel, Dan; Brodie, Chaya; Popovtzer, Rachela

2015-12-28

Diabetes mellitus is a chronic metabolic disease, characterized by high blood glucose levels, affecting millions of people around the world. Currently, the main treatment for diabetes requires multiple daily injections of insulin and self-monitoring of blood glucose levels, which markedly affect patients' quality of life. In this study we present a novel strategy for controlled and prolonged glucose regulation, based on the administration of insulin-coated gold nanoparticles (INS-GNPs). We show that both intravenous and subcutaneous injection of INS-GNPs into a mouse model of type 1 diabetes decreases blood glucose levels for periods over 3 times longer than free insulin. We further showed that conjugation of insulin to GNPs prevented its rapid degradation by the insulin-degrading-enzyme, and thus allows controlled and adjustable bio-activity. Moreover, we assessed different sizes and concentrations of INS-GNPs, and found that both parameters have a critical effect in vivo, enabling specific adjustment of blood glucose levels. These findings have the potential to improve patient compliance in diabetes mellitus.

Insulin-coated gold nanoparticles as a new concept for personalized and adjustable glucose regulation

NASA Astrophysics Data System (ADS)

Shilo, Malka; Berenstein, Peter; Dreifuss, Tamar; Nash, Yuval; Goldsmith, Guy; Kazimirsky, Gila; Motiei, Menachem; Frenkel, Dan; Brodie, Chaya; Popovtzer, Rachela

2015-12-01

Diabetes mellitus is a chronic metabolic disease, characterized by high blood glucose levels, affecting millions of people around the world. Currently, the main treatment for diabetes requires multiple daily injections of insulin and self-monitoring of blood glucose levels, which markedly affect patients' quality of life. In this study we present a novel strategy for controlled and prolonged glucose regulation, based on the administration of insulin-coated gold nanoparticles (INS-GNPs). We show that both intravenous and subcutaneous injection of INS-GNPs into a mouse model of type 1 diabetes decreases blood glucose levels for periods over 3 times longer than free insulin. We further showed that conjugation of insulin to GNPs prevented its rapid degradation by the insulin-degrading-enzyme, and thus allows controlled and adjustable bio-activity. Moreover, we assessed different sizes and concentrations of INS-GNPs, and found that both parameters have a critical effect in vivo, enabling specific adjustment of blood glucose levels. These findings have the potential to improve patient compliance in diabetes mellitus.

How to design a biosensor.

PubMed

Ward, W Kenneth

2007-03-01

Amperometric sensors for continuous glucose monitoring could prevent acute and chronic complications of diabetes, but research is needed to improve accuracy and stability. In designing sensors, interference from non-glucose analytes can be minimized by use of filtration membranes or electron transfer mediators that allow polarization at low potentials. If oxygen is required for the enzymatic reaction with glucose, then the outer permselective membrane must have substantial oxygen permeability. For this reason, during development of permselective membranes, permeability studies (such as performed by Tipnis and colleagues in this issue) can be used to measure transport of glucose and oxygen and optimize membrane structure. Tipnis and colleagues present a novel biosensor based with separate layers for glucose-oxygen permselectivity, enzymatic conversion, and avoidance of interference. They also address sensor stability, in part by comparing sensor function during ascending vs descending glucose levels. By measuring the difference, they were able to minimize this aspect of instability (hysterisis), which assisted them in selecting a promising permselective membrane based on iron and humic acid.

Characterization of Porous, Dexamethasone-Releasing Polyurethane Coatings for Glucose Sensors

PubMed Central

Vallejo-Heligon, Suzana G.; Klitzman, Bruce; Reichert, William M.

2014-01-01

Commercially available implantable needle-type glucose sensors for diabetes management are robust analytically but can be unreliable clinically primarily due to tissue-sensor interactions. Here, we present the physical, drug release, and bioactivity characterization of tubular, porous dexamethasone (Dex) releasing polyurethane coatings designed to attenuate local inflammation in the tissue-sensor interface. Porous polyurethane coatings were produced by the salt-leaching/gas-foaming method. Scanning electron microscopy (SEM) and Micro-computed tomography (Micro-CT) showed a controlled porosity and coating thickness. In vitro drug release from coatings monitored over two weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture. Acute animal studies were used to determine the appropriate Dex payload for the implanted porous coatings. Pilot short-term animal studies showed that Dex released from porous coatings implanted in rat subcutis attenuated the initial inflammatory response to sensor implantation. These results suggest that deploying sensors with the porous, Dex-releasing coatings is a promising strategy to improve glucose sensor performance. PMID:25065548

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain.

PubMed

Jensen, Vivi F H; Mølck, Anne-Marie; Chapman, Melissa; Alifrangis, Lene; Andersen, Lene; Lykkesfeldt, Jens; Bøgh, Ingrid B

2017-01-01

The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

Effect of aqueous extract of tops of date palm leaves on blood glucose of diabetic rats.

PubMed

Ismail, Mohamed Saleh; Abuzaid, Omar Ibrahim; El-Ashmawy, Ibrahim Mohamed

2017-09-01

Present study was carried out to examine the effect of tops of date palm leaves extract on blood glucose of streptozotocin induced diabetic rats. Forty male Sprague Dawely rats (120-130g) were housed individually and randomly allocated to two main groups; diabetic group (n=30), and normal group (n=10) in the animal lab, Faculty of Agriculture and Veterinary Medicine, Qassim University, Saudi Arabia. An aqueous extracts were prepared from tops of date palm leaves (EDPL) and were orally administered to rats. Later, the determination of glucose, BUN, creatinine, uric acid, ALT, and AST was examined. Pancreas sample were taken for histopathological examination. It was clear that the higher the concentration of EDPL the lower the weight gain (P<0.001). Glucose concentration of normal group changed by - 0.79% and decreased by -20.4% among diabetic control group, while feeding 1% and 2% EDPL had no significant effects, and the higher the amount of EDPL the higher the concentration of blood glucose. The thought that tea made from date palm leaves decrease blood glucose level has been denied by the results of this study and this tea may worsen diabetes patient's status.

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study

PubMed Central

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-01-01

Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21–64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140–187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30–120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0–2 h (AUC0–2 h) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe. PMID:27882216

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

PubMed

Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

2016-11-01

Kale ( Brassica oleracea var. acephala ), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (C max ; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0-2 h (AUC 0-2 h ) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

Central Composite Design (CCD) applied for statistical optimization of glucose and sucrose binary carbon mixture in enhancing the denitrification process

NASA Astrophysics Data System (ADS)

Lim, Jun-Wei; Beh, Hoe-Guan; Ching, Dennis Ling Chuan; Ho, Yeek-Chia; Baloo, Lavania; Bashir, Mohammed J. K.; Wee, Seng-Kew

2017-11-01

The present study provides an insight into the optimization of a glucose and sucrose mixture to enhance the denitrification process. Central Composite Design was applied to design the batch experiments with the factors of glucose and sucrose measured as carbon-to-nitrogen (C:N) ratio each and the response of percentage removal of nitrate-nitrogen (NO3 --N). Results showed that the polynomial regression model of NO3 --N removal had been successfully derived, capable of describing the interactive relationships of glucose and sucrose mixture that influenced the denitrification process. Furthermore, the presence of glucose was noticed to have more consequential effect on NO3 --N removal as opposed to sucrose. The optimum carbon sources mixture to achieve complete removal of NO3 --N required lesser glucose (C:N ratio of 1.0:1.0) than sucrose (C:N ratio of 2.4:1.0). At the optimum glucose and sucrose mixture, the activated sludge showed faster acclimation towards glucose used to perform the denitrification process. Later upon the acclimation with sucrose, the glucose uptake rate by the activated sludge abated. Therefore, it is vital to optimize the added carbon sources mixture to ensure the rapid and complete removal of NO3 --N via the denitrification process.

Glucose-dependent and Glucose-sensitizing Insulinotropic Effect of Nateglinide: Comparison to Sulfonylureas and Repaglinide

PubMed Central

Wang, Shuya; Dunning, Beth E.

2001-01-01

Nateglinide, a novel D-phenylalanine derivative, stimulates insulin release via closure of KATP channels in pancreatic β-cell, a primary mechanism of action it shares with sulfonylureas (SUs) and repaglinide. This study investigated (1) the influence of ambient glucose levels on the insulinotropic effects of nateglinide, glyburide and repaglinide, and (2) the influence of the antidiabetic agents on glucose-stimulated insulin secretion (GSIS) in vitro from isolated rat islets. The EC50 of nateglinide to stimulate insulin secretion was 14 μM in the presence of 3mM glucose and was reduced by 6-fold in 8mM glucose and by 16-fold in 16mM glucose, indicating a glucose-dependent insulinotropic effect. The actions of glyburide and repaglinide failed to demonstrate such a glucose concentration-dependent sensitization. When tested at fixed and equipotent concentrations (~2x EC50 in the presence of 8mM glucose) nateglinide and repaglinide shifted the EC50s for GSIS to the left by 1.7mM suggesting an enhancement of islet glucose sensitivity, while glimepiride and glyburide caused, respectively, no change and a right shift of the EC50. These data demonstrate that despite a common basic mechanism of action, the insulinotropic effects of different agents can be influenced differentially by ambient glucose and can differentially influence the islet responsiveness to glucose. Further, the present findings suggest that nateglinide may exert a more physiologic effect on insulin secretion than comparator agents and thereby have less propensity to elicit hypoglycemia in vivo. PMID:12369728

Study on the mechanism of human blood glucose concentration measuring using mid-infrared spectral analysis technology

NASA Astrophysics Data System (ADS)

Li, Xiang

2016-10-01

All forms of diabetes increase the risk of long-term complications. Blood glucose monitoring is of great importance for controlling diabetes procedure, preventing the complications and improving the patient's life quality. At present, the clinical blood glucose concentration measurement is invasive and could be replaced by noninvasive spectroscopy analytical techniques. The mid-infrared spectral region contains strong characteristic and well-defined absorption bands. Therefore, mid-infrared provides an opportunity for monitoring blood glucose invasively with only a few discrete bonds. Although the blood glucose concentration measurement using mid-infrared spectroscopy has a lot of advantages, the disadvantage is also obvious. The absorption in this infrared region is fundamental molecular group vibration. Absorption intensity is very strong, especially for biological molecules. In this paper, it figures out that the osmosis rate of glucose has a certain relationship with the blood glucose concentration. Therefore, blood glucose concentration could be measured indirectly by measuring the glucose exudate in epidermis layer. Human oral glucose tolerance tests were carried out to verify the correlation of glucose exudation in shallow layer of epidermis layer and blood glucose concentration. As it has been explained above, the mid-infrared spectral region contains well-defined absorption bands, the intensity of absorption peak around 1123 cm-1 was selected to measure the glucose and that around 1170 cm-1 was selected as reference. Ratio of absorption peak intensity was recorded for each set of measurement. The effect and importance of the cleaning the finger to be measured before spectrum measuring are discussed and also verified by experiment.

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conde, Vanessa R.; Oliveira, Pedro F.; Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similarmore » in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.« less

Model-Based Closed-Loop Glucose Control in Type 1 Diabetes: The DiaCon Experience

PubMed Central

Schmidt, Signe; Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Frøssing, Laurits; Skyggebjerg, Ole; Jørgensen, John Bagterp; Poulsen, Niels Kjølstad; Madsen, Henrik; Madsbad, Sten; Nørgaard, Kirsten

2013-01-01

Background To improve type 1 diabetes mellitus (T1DM) management, we developed a model predictive control (MPC) algorithm for closed-loop (CL) glucose control based on a linear second-order deterministic-stochastic model. The deterministic part of the model is specified by three patient-specific parameters: insulin sensitivity factor, insulin action time, and basal insulin infusion rate. The stochastic part is identical for all patients but identified from data from a single patient. Results of the first clinical feasibility test of the algorithm are presented. Methods We conducted two randomized crossover studies. Study 1 compared CL with open-loop (OL) control. Study 2 compared glucose control after CL initiation in the euglycemic (CL-Eu) and hyperglycemic (CL-Hyper) ranges, respectively. Patients were studied from 22:00–07:00 on two separate nights. Results Each study included six T1DM patients (hemoglobin A1c 7.2% ± 0.4%). In study 1, hypoglycemic events (plasma glucose < 54 mg/dl) occurred on two OL and one CL nights. Average glucose from 22:00–07:00 was 90 mg/dl [74–146 mg/dl; median (interquartile range)] during OL and 108 mg/dl (101–128 mg/dl) during CL (determined by continuous glucose monitoring). However, median time spent in the range 70–144 mg/dl was 67.9% (3.0–73.3%) during OL and 80.8% (70.5–89.7%) during CL. In study 2, there was one episode of hypoglycemia with plasma glucose <54 mg/dl in a CL-Eu night. Mean glucose from 22:00–07:00 and time spent in the range 70–144 mg/dl were 121 mg/dl (117–133 mg/dl) and 69.0% (30.7–77.9%) in CL-Eu and 149 mg/dl (140–193 mg/dl) and 48.2% (34.9–72.5%) in CL-Hyper, respectively. Conclusions This study suggests that our novel MPC algorithm can safely and effectively control glucose overnight, also when CL control is initiated during hyperglycemia. PMID:24124952

IR-IR Conformation Specific Spectroscopy of Na +(Glucose) Adducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voss, Jonathan M.; Kregel, Steven J.; Fischer, Kaitlyn C.

Here in this paper we report an IR-IR double resonance study of the structural landscape present in the Na +(glucose) complex. Our experimental approach involves minimal modifications to a typical IR predissociation setup, and can be carried out via ion-dip or isomer-burning methods, providing additional flexibility to suit different experimental needs. In the current study, the single-laser IR predissociation spectrum of Na +(glucose), which clearly indicates contributions from multiple structures, was experimentally disentangled to reveal the presence of three α-conformers and five β-conformers. Comparisons with calculations show that these eight conformations correspond to the lowest energy gas-phase structures with distinctivemore » Na+ coordination.« less

IR-IR Conformation Specific Spectroscopy of Na +(Glucose) Adducts

DOE PAGES

Voss, Jonathan M.; Kregel, Steven J.; Fischer, Kaitlyn C.; ...

2017-09-27

Here in this paper we report an IR-IR double resonance study of the structural landscape present in the Na +(glucose) complex. Our experimental approach involves minimal modifications to a typical IR predissociation setup, and can be carried out via ion-dip or isomer-burning methods, providing additional flexibility to suit different experimental needs. In the current study, the single-laser IR predissociation spectrum of Na +(glucose), which clearly indicates contributions from multiple structures, was experimentally disentangled to reveal the presence of three α-conformers and five β-conformers. Comparisons with calculations show that these eight conformations correspond to the lowest energy gas-phase structures with distinctivemore » Na+ coordination.« less

Circadian system and glucose metabolism: implications for physiology and disease

PubMed Central

Qian, Jingyi; Scheer, Frank AJL

2016-01-01

The circadian system serves one of the most fundamental properties present in nearly all organisms: it generates 24-hr rhythms in behavioral and physiological processes and enables anticipating and adapting to daily environmental changes. Recent studies indicate that the circadian system is important in regulating the daily rhythm in glucose metabolism. Disturbance of this circadian control or of its coordination relative to the environmental/behavioral cycle, such as in shift work, eating late or due to genetic changes, results in disturbed glucose control and increased type 2 diabetes risk. Therefore, an in-depth understanding of the mechanisms underlying glucose regulation by the circadian system and its disturbance may help in the development of therapeutic interventions against the deleterious health consequences of circadian disruption. PMID:27079518

Role of glycemic elements of Cynodon dactylon and Musa paradisiaca in diabetes management.

PubMed

Rai, Prashant Kumar; Jaiswal, Dolly; Rai, Nilesh K; Pandhija, Shiwani; Rai, A K; Watal, Geeta

2009-09-01

The study defined the scientific evaluation of glycemic elements of extracts of Cynodon dactylon and Musa paradisiaca. A dose of 500 mg/kg body weight (bw) of C. dactylon produced maximum falls of 23.2% and 22.8% in blood glucose levels of normoglycemic rats during studies of fasting blood glucose and glucose tolerance, respectively, whereas the same dose of M. paradisiaca produced a rise of 34.9% and 18.4%. In diabetic rats during glucose tolerance tests, a fall of 27.8% and a rise of 17.5% were observed with the same dose of C. dactylon and M. paradisiaca, respectively. Laser-induced breakdown spectroscopy used for detection of glycemic elements present in both the extracts indicated that C. dactylon was rich in magnesium (Mg), whereas M. paradisiaca was rich in potassium (K) and sodium (Na), comparatively, suggesting thereby the defined roles of these elements in diabetes management.

Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression.

PubMed

Serebrovska, Tetiana V; Portnychenko, Alla G; Drevytska, Tetiana I; Portnichenko, Vladimir I; Xi, Lei; Egorov, Egor; Gavalko, Anna V; Naskalova, Svitlana; Chizhova, Valentina; Shatylo, Valeriy B

2017-09-01

The present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1α (HIF-1α) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1α mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1α target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1α was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes. Impact statement The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1α mRNA expressions as well as its target genes, which were positively correlated with higher tolerance to acute hypoxia and better glucose homeostasis in both middle-aged healthy and prediabetic subjects. This small clinical trial has provided new data suggesting a potential utility of IHT for management of prediabetes patients.

Porous, Dexamethasone-loaded polyurethane coatings extend performance window of implantable glucose sensors in vivo.

PubMed

Vallejo-Heligon, Suzana G; Brown, Nga L; Reichert, William M; Klitzman, Bruce

2016-01-01

Continuous glucose sensors offer the promise of tight glycemic control for insulin dependent diabetics; however, utilization of such systems has been hindered by issues of tissue compatibility. Here we report on the in vivo performance of implanted glucose sensors coated with Dexamethasone-loaded (Dex-loaded) porous coatings employed to mediate the tissue-sensor interface. Two animal studies were conducted to (1) characterize the tissue modifying effects of the porous Dex-loaded coatings deployed on sensor surrogate implants and (2) investigate the effects of the same coatings on the in vivo performance of Medtronic MiniMed SOF-SENSOR™ glucose sensors. The tissue response to implants was evaluated by quantifying macrophage infiltration, blood vessel formation, and collagen density around implants. Sensor function was assessed by measuring changes in sensor sensitivity and time lag, calculating the Mean Absolute Relative Difference (MARD) for each sensor treatment, and performing functional glucose challenge test at relevant time points. Implants treated with porous Dex-loaded coatings diminished inflammation and enhanced vascularization of the tissue surrounding the implants. Functional sensors with Dex-loaded porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicate that Dex-loaded porous coatings were able to elicit an attenuated tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo. In the present article, a coating to extend the functionality of implantable glucose sensors in vivo was developed. Our study showed that the delivery of an anti-inflammatory agent with the presentation of micro-sized topographical cues from coatings may lead to improved long-term glucose sensor function in vivo. We believe that improved function of sensors treated with the novel coatings was a result of the observed decreases in inflammatory cell density and increases in vessel density of the tissue adjacent to the devices. Furthermore, extending the in vivo functionality of implantable glucose sensors may lead to greater adoption of these devices by diabetic patients. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Assessing the Analytical Performance of Systems for Self-Monitoring of Blood Glucose: Concepts of Performance Evaluation and Definition of Metrological Key Terms

PubMed Central

Schnell, Oliver; Hinzmann, Rolf; Kulzer, Bernd; Freckmann, Guido; Erbach, Michael; Lodwig, Volker; Heinemann, Lutz

2013-01-01

Reliability of blood glucose (BG) measurements is a prerequisite for successful diabetes management. Publications on the evaluation of self-monitored glucose values, however, are frequently characterized by a confusion in terminology. We provide an inventory of key terms such as accuracy, trueness, precision, traceability, calibration, and matrix effect to avoid future misunderstanding. Definitions are taken from the metrological literature and international norms and explained in a language intended for nonspecialists in metrology. The terms are presented in light of the need to apply generally accepted definitions. In addition, a description of requirements and components for a sound evaluation of BG measurement systems is presented. These factors will also enable improvement in future comparisons of study results. PMID:24351185

Growth yields and fermentation balance of Bacteroides fragilis cultured in glucose-enriched medium.

PubMed

Frantz, J C; McCallum, R E

1979-03-01

Bacteroides fragilis is an obligate anaerobic bacterium classified with the gram-negative, non-sporeforming bacilli and is the Bacteroides species most frequently isolated from human infections. In the present study, experiments were designed to investigate growth characteristics of B. fragilis in a complex medium. In a minimal defined medium, which was employed for comparison purposes, B. fragilis grew with a generation time of 2 h. Growth of the organism in glucose-enriched medium used in the present study was superior. Maximum generation time was 60 min. Total and viable cells (colony-forming units) were 8.9 x 10(9) and 2.1 x 10(9), respectively, at maximum measurable growth. The molar growth yield (Ym) was 51.5. Growth yields were found to reach a maximum 2 to 3 h before maximum growth and to vary with respect to the phase of growth. Estimates of the fermentation products indicated that glucose was the sole energy substrate. Major products included acetic acid, propionic acid, lactic acid, and succinic acid. Other products included ethyl alcohol, pyruvic acid, and fumaric acid. No attempt was made to recover CO2 or formic acid. The OR balances from two experiments were 0.013 and -0.093 and the respective carbon recoveries were 6.268 and 6.241. The results of the present study show that B. fragilis is capable of rapid rates of growth in vitro by using glucose as the sole energy source.

Osmoregulated periplasmic glucans synthesis gene family of Shigella flexneri

USDA-ARS?s Scientific Manuscript database

Osmoregulated periplasmic glucans (OPGs) of foodborne enteropathogen Shigella flexneri were characterized. OPGs were composed of 100 percent glucose with 2-linked glucose as the most abundant residue with terminal glucose, 2-linked and 2,6-linked glucose also present in high quantities. Most dominan...

A strategy for the highly efficient production of docosahexaenoic acid by Aurantiochytrium limacinum SR21 using glucose and glycerol as the mixed carbon sources.

PubMed

Li, Jing; Liu, Ruijie; Chang, Guifang; Li, Xiangyu; Chang, Ming; Liu, Yuanfa; Jin, Qingzhe; Wang, Xingguo

2015-02-01

Glucose and glycerol are useful carbon sources for the cultivation of Aurantiochytrium limacinum SR21. Glucose facilitates rapid growth and lipid synthesis, and glycerol promotes the accumulation of docosahexaenoic acid (DHA) in A. limacinum SR21. To improve the DHA productivity of A. limacinum SR21, shake flask and fed-batch cultures were performed using glucose and glycerol as mixed carbon sources (MCSs). Along with optimization of the MCSs, the best DHA yield and productivity (32.36 g/L and 337.1 mg/L/h) were obtained via fed-batch fermentation with maintenance of a constant air supply. The DHA productivity was 15.24% higher than that obtained using glucose as single carbon source (SCS). This study presents a highly efficient and economic strategy for the production of DHA by A. limacinum SR21. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Luffa aegyptiaca (seeds) and Carissa edulis (leaves) extracts on blood glucose level of normal and streptozotocin diabetic rats.

PubMed

El-Fiky, F K; Abou-Karam, M A; Afify, E A

1996-01-01

The present study investigates the effect of oral administration of the ethanolic extracts of Luffa aegyptiaca (seeds) and Carissa edulis (leaves) on blood glucose levels both in normal and streptozotocin (STZ) diabetic rats. Treatment with both extracts significantly reduced the blood glucose level in STZ diabetic rats during the first three hours of treatment. L. aegyptiaca extract decreased blood glucose level with a potency similar to that of the biguanide, metformin. The total glycaemic areas were 589.61 +/- 45.62 mg/dl/3 h and 660.38 +/- 64.44 mg/dl/3 h for L. aegyptiaca and metformin, respectively, vs. 816.73 +/- 43.21 mg/dl/3 h for the control (P < 0.05). On the other hand, in normal rats, both treatments produced insignificant changes in blood glucose levels compared to glibenclamide treatment.

Proportional Insulin Infusion in Closed-Loop Control of Blood Glucose

PubMed Central

Grasman, Johan

2017-01-01

A differential equation model is formulated that describes the dynamics of glucose concentration in blood circulation. The model accounts for the intake of food, expenditure of calories and the control of glucose levels by insulin and glucagon. These and other hormones affect the blood glucose level in various ways. In this study only main effects are taken into consideration. Moreover, by making a quasi-steady state approximation the model is reduced to a single nonlinear differential equation of which parameters are fit to data from healthy subjects. Feedback provided by insulin plays a key role in the control of the blood glucose level. Reduced β-cell function and insulin resistance may hamper this process. With the present model it is shown how by closed-loop control these defects, in an organic way, can be compensated with continuous infusion of exogenous insulin. PMID:28060898

Substance P enhances the activation of AMPK and cellular lipid accumulation in 3T3‑L1 cells in response to high levels of glucose.

PubMed

Dubon, Maria Jose; Byeon, Yeji; Park, Ki-Sook

2015-12-01

The rescue of glucose tolerance and insulin‑sensitivity in peripheral tissues, including adipose tissue, is essential in therapeutic strategies for diabetes. The present study demonstrated that substance P (SP) increases the accumulation of lipids in 3T3‑L1 cells during their differentiation into adipocytes in response to a high concentration of glucose. SP reciprocally regulated the activities of AMP‑activated protein kinase (AMPK) and Akt: SP enhanced the activation of AMPK, although the activity of Akt was downregulated. Notably, SP induced an increase in the expression level of glucose transporter 4 in the 3T3‑L1 adipocytes. Therefore, it is possible that SP leads to an increase in glucose uptake and the accumulation of lipids in adipocytes, and may contribute towards the rescue of insulin‑sensitivity in diabetes.

Nickel-Cobalt Oxide Decorated Three-Dimensional Graphene as an Enzyme Mimic for Glucose and Calcium Detection.

PubMed

Wu, Meiyan; Meng, Shangjun; Wang, Qian; Si, Weili; Huang, Wei; Dong, Xiaochen

2015-09-30

Glucose and calcium ion play key roles in human bodies. The needlelike NiCo2O4 nanostructures are in situ deposited on three-dimensional graphene foam (3DGF) by a facile hydrothermal procedure. The structure and morphology of the hierarchical NiCo2O4/3DGF are characterized by scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. With the self-standing NiCo2O4/3DGF as electrochemical electrode, it can realize the high-sensitivity detections for glucose and calcium ion. The limit of detection can reach 0.38 and 4.45 μM, respectively. In addition, the electrochemical electrode presents excellent selectivity for glucose and calcium ion. This study demonstrates that NiCo2O4/3DGF is a unique and promising material for practical application in both glucose and calcium ion sensing.

Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

PubMed

Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

2005-10-01

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

Stimulation of glucose uptake by Musa sp. (cv. elakki bale) flower and pseudostem extracts in Ehrlich ascites tumor cells.

PubMed

Bhaskar, Jamuna J; Salimath, Paramahans V; Nandini, Chilkunda D

2011-06-01

Glucose uptake study plays a major role in diabetes research. Impaired glucose uptake has been implicated in the development of hyperglycemia during diabetes. Banana plant is known for its anti-diabetic properties and our earlier report revealed that banana flower and pseudostem of Musa sp. cv. elakki bale is beneficial during diabetes in rat models. The present study was designed to evaluate the potential effect of banana flower and pseudostem extracts on glucose uptake in Ehrlich ascites tumor (EAT) cells using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a fluorescent analogue of 2-deoxyglucose. Methanol and aqueous extracts of banana flower and pseudostem were more potent in promoting glucose uptake in EAT cells, in comparison to acetone and ethanol extracts. At 20 µg dosage, highest net glucose uptake was observed in aqueous extracts of banana flower (18.17 ± 0.43 nmol L⁻¹) and pseudostem (19.69 ± 0.41 nmol L⁻¹). Total polyphenol content was higher in methanol (9.031 ± 0.036 g kg⁻¹) and aqueous (6.862 ± 0.024 g kg⁻¹) extracts of banana flower compared to pseudostem, which were 0.442 ± 0.006 and 0.811 ± 0.011 g kg⁻¹, respectively. Banana flower and pseudostem extracts are able to promote glucose uptake into the cells, presumably through glucose transporters 1 and 3, which could be beneficial in diabetes. Glucose uptake is likely promoted by phenolic acids besides other bioactives. It can be hypothesized that consumption of nutraceutical-rich extract of banana flower and pseudostem could replace some amount of insulin being taken for diabetes. Copyright © 2011 Society of Chemical Industry.

Structural Explanation for Allolactose (lac Operon Inducer) Synthesis by lacZ β-Galactosidase and the Evolutionary Relationship between Allolactose Synthesis and the lac Repressor

PubMed Central

Wheatley, Robert W.; Lo, Summie; Jancewicz, Larisa J.; Dugdale, Megan L.; Huber, Reuben E.

2013-01-01

β-Galactosidase (lacZ) has bifunctional activity. It hydrolyzes lactose to galactose and glucose and catalyzes the intramolecular isomerization of lactose to allolactose, the lac operon inducer. β-Galactosidase promotes the isomerization by means of an acceptor site that binds glucose after its cleavage from lactose and thus delays its exit from the site. However, because of its relatively low affinity for glucose, details of this site have remained elusive. We present structural data mapping the glucose site based on a substituted enzyme (G794A-β-galactosidase) that traps allolactose. Various lines of evidence indicate that the glucose of the trapped allolactose is in the acceptor position. The evidence includes structures with Bis-Tris (2,2-bis(hydroxymethyl)-2,2′,2″-nitrilotriethanol) and l-ribose in the site and kinetic binding studies with substituted β-galactosidases. The site is composed of Asn-102, His-418, Lys-517, Ser-796, Glu-797, and Trp-999. Ser-796 and Glu-797 are part of a loop (residues 795–803) that closes over the active site. This loop appears essential for the bifunctional nature of the enzyme because it helps form the glucose binding site. In addition, because the loop is mobile, glucose binding is transient, allowing the release of some glucose. Bioinformatics studies showed that the residues important for interacting with glucose are only conserved in a subset of related enzymes. Thus, intramolecular isomerization is not a universal feature of β-galactosidases. Genomic analyses indicated that lac repressors were co-selected only within the conserved subset. This shows that the glucose binding site of β-galactosidase played an important role in lac operon evolution. PMID:23486479

Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Jing; Gupta, Ramesh C.; Goad, John T.

2007-03-15

Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with nomore » significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation.« less

Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway.

PubMed

Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

2016-12-09

Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na⁺-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C ) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway

PubMed Central

Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

2016-01-01

Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na+-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway. PMID:27941667

Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeltchan, R., E-mail: r.zelchan@yandex.ru; Medvedeva, A.; Sinilkin, I.

Purpose: to study the potential utility of 1-thio-D-glucose labeled with {sup 99m}Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of {sup 99m}Tc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with {sup 99m}Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normalmore » and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of {sup 99m}Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with {sup 99m}Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of {sup 99m}Tc-1-thio-D-glucose at the tumor site. The accumulation of {sup 99m}Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that {sup 99m}Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of {sup 99m}Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.« less

Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.

2016-06-01

Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

2016-08-01

Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

Short-term effects of replacing milk with cola beverages on insulin-like growth factor-I and insulin-glucose metabolism: a 10 d interventional study in young men.

PubMed

Hoppe, Camilla; Kristensen, Mette; Boiesen, Marlene; Kudsk, Jane; Fleischer Michaelsen, Kim; Mølgaard, Christian

2009-10-01

In the Western world, a trend towards increased consumption of carbonated soft drinks combined with a decreasing intake of milk is observed. This may affect circulating insulin-like growth factor I (IGF-I) and fasting insulin, as seen in pre-pubertal children. The present study was designed to reflect the trend of replacing milk with carbonated beverages in young men and to study the effects of this replacement on IGF-I, IGF-binding protein 3 (IGFBP-3), IGF-I:IGFBP-3 and glucose-insulin metabolism. A randomised, controlled crossover intervention study, in which eleven men aged 22-29 years were given a low-Ca diet in two 10 d periods with 10 d washout in between. In one period, they drank 2.5 litres of Coca Cola(R) per day and the other period 2.5 litres of semi-skimmed milk. Serum IGF-I, IGFBP-3 (RIA), insulin (fluoro immunoassay) and glucose (Cobas) were determined at baseline and end point of each intervention period. Insulin resistance and beta-cell function were calculated with the homeostasis model assessment. A decrease in serum IGF-I was observed in the cola period compared with the milk period (P < 0.05). No effects of treatment were observed on IGFBP-3, IGF-I:IGFBP-3, insulin, glucose, insulin resistance or beta-cell function. The present study demonstrates that high intake of cola over a 10 d period decreases total IGF-I compared with a high intake of milk, with no effect on glucose-insulin metabolism in adult men. It is unknown whether this is a transient phenomenon or whether it has long-term consequences.

Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study

PubMed Central

Yellapu, Nanda Kumar; Kandlapalli, Kalpana; Valasani, Koteswara Rao; Sarma, P. V. G. K.; Matcha, Bhaskar

2013-01-01

Glucokinase (GK) is the predominant hexokinase that acts as glucose sensor and catalyses the formation of Glucose-6-phosphate. The mutations in GK gene influence the affinity for glucose and lead to altered glucose levels in blood causing maturity onset diabetes of the young type 2 (MODY2) condition, which is one of the prominent reasons of type 2 diabetic condition. In view of the importance of mutated GK resulting in hyperglycemic condition, in the present study, molecular dynamics simulations were carried out in intact and 256 E-K mutated GK structures and their energy values and conformational variations were correlated. Energy variations were observed in mutated GK (3500 Kcal/mol) structure with respect to intact GK (5000 Kcal/mol), and it showed increased γ-turns, decreased β-turns, and more helix-helix interactions that affected substrate binding region where its volume increased from 1089.152 Å2 to 1246.353 Å2. Molecular docking study revealed variation in docking scores (intact = −12.199 and mutated = −8.383) and binding mode of glucose in the active site of mutated GK where the involvement of A53, S54, K56, K256, D262 and Q286 has resulted in poor glucose binding which probably explains the loss of catalytic activity and the consequent prevailing of high glucose levels in MODY2 condition. PMID:23476789

NMR analyses of complex d-glucose anomerization.

PubMed

Kaufmann, Martin; Mügge, Clemens; Kroh, Lothar W

2018-11-01

Analyzing the 1 H NMR spectrum of d-glucose, the resonance frequencies of the anomeric protons of five d-glucose anomers could be determined in dependence on temperature. Besides, the relative concentrations of all cyclic d-glucose anomers could be quantified. Based on that, thermodynamic parameters were calculated. In addition, ring opening rate constants of all cyclic d-glucose anomers were measured for the first time using 1 H selective blind saturation transfer NMR spectroscopy. The results presented here give rise to the assumption that furanoid anomers highly influence the reactivity of total d-glucose. Finally, the complex anomeric equilibration curves for a freshly prepared solution of crystalline α-d-glucopyranose are presented. Based on that, it is hypothesized that the reactivity of a solution of a reducing sugar in general and d-glucose in particular depends on time until the thermodynamic equilibrium state is reached. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fructose utilization during exercise in men: rapid conversion of ingested fructose to circulating glucose.

PubMed

Jandrain, B J; Pallikarakis, N; Normand, S; Pirnay, F; Lacroix, M; Mosora, F; Pachiaudi, C; Gautier, J F; Scheen, A J; Riou, J P

1993-05-01

The aim of the present study was to compare the metabolic fate of repeated doses of fructose or glucose ingested every 30 min during long-duration moderate-intensity exercise in men. Healthy volunteers exercised for 3 h on a treadmill at 45% of their maximal oxygen consumption rate. "Naturally labeled" [13C]glucose or [13C]fructose was given orally at 25-g doses every 30 min (total feeding: 150 g; n = 6 in each group). Substrate utilization was evaluated by indirect calorimetry, and exogenous sugar oxidation was measured by isotope ratio mass spectrometry on expired CO2. Results were corrected for baseline drift in 13C/12C ratio in expired air due to exercise alone. Fructose conversion to plasma glucose was measured combining gas chromatography and isotope ratio mass spectrometry. Most of the ingested glucose was oxidized: 81 +/- 4 vs. 57 +/- 2 g/3 h for fructose (2P < 0.005). Exogenous glucose covered 20.8 +/- 1.4% of the total energy need (+/- 6.7 MJ) compared with 14.0 +/- 0.6% for fructose (2P < 0.005). The contribution of total carbohydrates was significantly higher and that of lipids significantly lower with glucose than with fructose. The blood glucose response was similar in both protocols. From 90 to 180 min, 55-60% of circulating glucose was derived from ingested fructose. In conclusion, when ingested repeatedly during moderate-intensity prolonged exercise, fructose is metabolically less available than glucose, despite a high rate of conversion to circulating glucose.

Educational intervention together with an on-line quality control program achieve recommended analytical goals for bedside blood glucose monitoring in a 1200-bed university hospital.

PubMed

Sánchez-Margalet, Víctor; Rodriguez-Oliva, Manuel; Sánchez-Pozo, Cristina; Fernández-Gallardo, María Francisca; Goberna, Raimundo

2005-01-01

Portable meters for blood glucose concentrations are used at the patients bedside, as well as by patients for self-monitoring of blood glucose. Even though most devices have important technological advances that decrease operator error, the analytical goals proposed for the performance of glucose meters have been recently changed by the American Diabetes Association (ADA) to reach <5% analytical error and <7.9% total error. We studied 80 meters throughout the Virgen Macarena Hospital and we found most devices with performance error higher than 10%. The aim of the present study was to establish a new system to control portable glucose meters together with an educational program for nurses in a 1200-bed University Hospital to achieve recommended analytical goals, so that we could improve the quality of diabetes care. We used portable glucose meters connected on-line to the laboratory after an educational program for nurses with responsibilities in point-of-care testing. We evaluated the system by assessing total error of the glucometers using high- and low-level glucose control solutions. In a period of 6 months, we collected data from 5642 control samples obtained by 14 devices (Precision PCx) directly from the control program (QC manager). The average total error for the low-level glucose control (2.77 mmol/l) was 6.3% (range 5.5-7.6%), and even lower for the high-level glucose control (16.66 mmol/l), at 4.8% (range 4.1-6.5%). In conclusion, the performance of glucose meters used in our University Hospital with more than 1000 beds not only improved after the intervention, but the meters achieved the analytical goals of the suggested ADA/National Academy of Clinical Biochemistry criteria for total error (<7.9% in the range 2.77-16.66 mmol/l glucose) and optimal total error for high glucose concentrations of <5%, which will improve the quality of care of our patients.

New aspects in pathogenesis of konzo: neural cell damage directly caused by linamarin contained in cassava (Manihot esculenta Crantz).

PubMed

Sreeja, V G; Nagahara, N; Li, Q; Minami, M

2003-08-01

Epidemic spastic paraparesis (konzo) found in tropical and subtropical countries is known to be caused by long-term intake of cassava (Manihot esculenta Crantz), which contains a cyanoglucoside linamarin (alpha-hydroxyisobutyronitrile-beta-d-glucopyranoside). It has been reported that linamarin is enzymatically converted to cyanide by bacteria in the intestine, and this is absorbed into the blood and then damages neural cells. However, unmetabolized linamarin was found in the urine after oral administration of cassava; thus, we hypothesized that konzo could be caused by direct toxicity of the unmetabolized linamarin that was transferred to the brain and could be transported into neural cells via a glucose transporter. In the present study it was confirmed that linamarin directly damaged neural culture pheochromocytoma cell (PC) 12 cells; 0.10 mm-linamarin caused cell death at 13.31 (SD 2.07) %, which was significantly different from that of control group (3.18 (SD 0.92) %, P=0.0004). Additional 10 microM-cytochalasin B, an inhibitor of a glucose transporter, prevented cell death: the percentage of dead cells significantly decreased to 6.06 (SD 1.98), P=0.0088). Furthermore, glucose also prevented cell death. These present results strongly suggest that linamarin competes with cytochalasin B and glucose for binding to a glucose transporter and enters into cells via glucose transporter.

Institutional blood glucose monitoring system for hospitalized patients: an integral component of the inpatient glucose control program.

PubMed

Boaz, Mona; Landau, Zohar; Matas, Zipora; Wainstein, Julio

2009-09-01

The ability to measure patient blood glucose levels at bedside in hospitalized patients and to transmit those values to a central database enables and facilitates glucose control and follow-up and is an integral component in the care of the hospitalized diabetic patient. The goal of this study was to evaluate the performance of an institutional glucometer employed in the framework of the Program for the Treatment of the Hospitalized Diabetic Patient (PTHDP) at E. Wolfson Medical Center, Holon, Israel. As part of the program to facilitate glucose control in hospitalized diabetic patients, an institutional glucometer was employed that permits uploading of data from stands located in each inpatient department and downloading of that data to a central hospital-wide database. Blood glucose values from hospitalized diabetic patients were collected from August 2007 to October 2008. The inpatient glucose control program was introduced gradually beginning January 2008. During the follow-up period, more than 150,000 blood glucose measures were taken. Mean glucose was 195.7 +/- 99.12 mg/dl during the follow-up period. Blood glucose values declined from 206 +/- 105 prior to PTHDP (August 2007-December 2007) to 186 +/- 92 after its inception (January 2008-October 2008). The decline was associated significantly with time (r = 0.11, p < 0.0001). The prevalence of blood glucose values lower than 60 mg/dl was 1.48% [95% confidence interval (CI) 0.36%] prior to vs 1.55% (95% CI 0.37%) following implementation of the PTHDP. Concomitantly, a significant increase in the proportion of blood glucose values between 80 and 200 mg/dl was observed, from 55.5% prior to program initiation vs 61.6% after program initiation (p < 0.0001). The present study was designed to observe changes in institution-wide glucose values following implementation of the PTHDP. Information was extracted from the glucometer system itself. Because the aforementioned study was not a clinical trial, we cannot rule out that factors other than introduction of the program could explain some of the variability observed. With these limitations in mind, it nevertheless appears that the PTHDP, of which the institutional glucometer is an integral, essential component, was associated with improved blood glucose values in the hospitalized diabetic patient. 2009 Diabetes Technology Society.

Fabrication of interdigitated high-performance zinc oxide nanowire modified electrodes for glucose sensing.

PubMed

Haarindraprasad, R; Hashim, Uda; Gopinath, Subash C B; Perumal, Veeradasan; Liu, Wei-Wen; Balakrishnan, S R

2016-06-21

Diabetes is a metabolic disease with a prolonged elevated level of glucose in the blood leads to long-term complications and increases the chances for cardiovascular diseases. The present study describes the fabrication of a ZnO nanowire (NW)-modified interdigitated electrode (IDE) to monitor the level of blood glucose. A silver IDE was generated by wet etching-assisted conventional lithography, with a gap between adjacent electrodes of 98.80 μm. The ZnO-based thin films and NWs were amended by sol-gel and hydrothermal routes. High-quality crystalline and c-axis orientated ZnO thin films were observed by XRD analyses. The ZnO thin film was annealed for 1, 3 and 5 h, yielding a good-quality crystallite with sizes of 50, 100 and 110 nm, and the band gaps were measured as 3.26, 3.20 and 3.17 eV, respectively. Furthermore, a flower-modeled NW was obtained with the lowest diameter of 21 nm. Our designed ZnO NW-modified IDE was shown to have a detection limit as low as 0.03 mg/dL (correlation coefficient = 0.98952) of glucose with a low response time of 3 s, perform better than commercial glucose meter, suitable to instantly monitor the glucose level of diabetes patients. This study demonstrated the high performance of NW-mediated IDEs for glucose sensing as alternative to current glucose sensors. Copyright © 2016 Elsevier B.V. All rights reserved.

Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

PubMed

Hafizur, Rahman M; Hameed, Abdul; Shukrana, Mishkat; Raza, Sayed Ali; Chishti, Sidra; Kabir, Nurul; Siddiqui, Rehan A

2015-02-15

Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro. Copyright © 2015 Elsevier GmbH. All rights reserved.

Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates insulin resistance by upregulating glucose transporter-4, peroxisome proliferator-activated receptor-gamma, adiponectin, and leptin levels in vitro.

PubMed

Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V; Manjunath, Kirangadur; Viswanatha, Gollapalle L; Ashok, Godavarthi

2016-01-01

The present study was undertaken to evaluate the effect of methanolic leaf extract of Gymnema sylvestre (MLGS) on glucose transport (GLUT) and insulin resistance in vitro. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) and GLUT-4 expression were assessed in L6 myotubes for concluding the GLUT activity, and adiponectin and leptin expression was studied in 3T3 L1 murine adipocyte cell line to determine the effect of MLGS (250-750 μg/ml) on insulin resistance. The findings of the experiments have demonstrated a significant and dose-dependent increase in glucose uptake in all the tested concentrations of MLGS, further the glucose uptake activity of MLGS (750 μg/ml) was at par with rosiglitazone (50 μg/ml). Concomitantly, MLGS has shown enhanced GLUT-4 and PPAR-γ gene expressions in L6 myotubes. Furthermore, cycloheximide (CHX) had completely abolished the glucose uptake activity of MLGS when co-incubated, which further confirmed that glucose uptake activity of MLGS was linked to enhanced expression of GLUT-4 and PPAR-γ. In addition, in another experimental set, MLGS showed enhanced expression of adiponectin and leptin, thus confirms the ameliorative effect of MLGS on insulin resistance. These findings suggest that MLGS has an enhanced glucose uptake activity in L6 myotubes, and ameliorate the insulin resistance in 3T3 L1 murine adipocyte cell line in vitro.

Glucose administration prior to a divided attention task improves tracking performance but not word recognition: evidence against differential memory enhancement?

PubMed

Scholey, Andrew B; Sünram-Lea, Sandra I; Greer, Joanna; Elliott, Jade; Kennedy, David O

2009-01-01

The cognition-enhancing effects of glucose administration to humans have been well-documented; however, it remains unclear whether this effect preferentially targets episodic memory or other cognitive domains. The effect of glucose on the allocation of attentional resources during memory encoding was assessed using a sensitive dual-attention paradigm. One hundred and twenty volunteers (mean age 21.60, SD 4.89, 77 females) took part in this randomised, double-blind, placebo-controlled, parallel groups study where each consumed a 25-g glucose drink or a placebo. Half of the participants in each drink condition attempted to track a moving on-screen target during auditory word presentation. The distance between the cursor and the tracking target was used as an index of attentional cost during encoding. Effects of drink and tracking on recognition memory and drink on tracking performance were assessed. Self-rated appetite and mood were co-monitored. Co-performing the tracking task significantly impaired memory performance irrespective of drink condition. In the placebo-tracking condition, there was a cost to tracking manifest as greater deviation from target during and immediately following word presentation. Compared with placebo, the glucose drink significantly improved tracking performance during encoding. There were significant time-related changes in thirst and alertness ratings but these were not differentially affected by drink or tracking conditions. Tracking but not memory was enhanced by glucose. This finding suggests that, under certain task conditions, glucose administrations does not preferentially enhance memory performance. One mechanism through which glucose acts as a cognition enhancer is through allowing greater allocation of attentional resources.

AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice

PubMed Central

Nakano, Kazuhiro; Takeshita, Sen; Kawasaki, Noriko; Miyanaga, Wataru; Okamatsu, Yoriko; Dohi, Mizuki; Nakagawa, Tadakiyo

2017-01-01

Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl) phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P). In vivo, we used ob/ob mice to evaluate the novel anti-diabetic effects of AJS1669 by measuring basal blood glucose levels, glucose tolerance and body fat mass index. Repeated administration of AJS1669 over 4 weeks reduced blood glucose and hemoglobin A1c (HbA1c) levels in ob/ob mice. AJS1669 also improved glucose tolerance in a dose-dependent manner, and decreased body fat mass. The mRNA levels of genes involved in mitochondrial fatty acid oxidation and mitochondrial biogenesis were elevated in skeletal muscle tissue following AJS1669 treatment. Hepatic tissue of treated mice also exhibited elevated expression of genes associated with fatty acid oxidation. In contrast to ob/ob mice, in C57Bl/6 mice AJS1669 administration did not alter body weight or reduce glucose levels. These results demonstrate that pharmacological agents that activate GYS1, the main GS subtype found in skeletal muscle, have potential for use as novel treatments for diabetes that improve glucose metabolism in skeletal muscle. PMID:28290602

AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice.

PubMed

Nakano, Kazuhiro; Takeshita, Sen; Kawasaki, Noriko; Miyanaga, Wataru; Okamatsu, Yoriko; Dohi, Mizuki; Nakagawa, Tadakiyo

2017-04-01

Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl)phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P). In vivo, we used ob/ob mice to evaluate the novel anti-diabetic effects of AJS1669 by measuring basal blood glucose levels, glucose tolerance and body fat mass index. Repeated administration of AJS1669 over 4 weeks reduced blood glucose and hemoglobin A1c (HbA1c) levels in ob/ob mice. AJS1669 also improved glucose tolerance in a dose-dependent manner, and decreased body fat mass. The mRNA levels of genes involved in mitochondrial fatty acid oxidation and mitochondrial biogenesis were elevated in skeletal muscle tissue following AJS1669 treatment. Hepatic tissue of treated mice also exhibited elevated expression of genes associated with fatty acid oxidation. In contrast to ob/ob mice, in C57Bl/6 mice AJS1669 administration did not alter body weight or reduce glucose levels. These results demonstrate that pharmacological agents that activate GYS1, the main GS subtype found in skeletal muscle, have potential for use as novel treatments for diabetes that improve glucose metabolism in skeletal muscle.

Kir6.2 Variant E23K Increases ATP-Sensitive K+ Channel Activity and Is Associated With Impaired Insulin Release and Enhanced Insulin Sensitivity in Adults With Normal Glucose Tolerance

PubMed Central

Villareal, Dennis T.; Koster, Joseph C.; Robertson, Heather; Akrouh, Alejandro; Miyake, Kazuaki; Bell, Graeme I.; Patterson, Bruce W.; Nichols, Colin G.; Polonsky, Kenneth S.

2009-01-01

OBJECTIVE The E23K variant in the Kir6.2 subunit of the ATP-sensitive K+ channel (KATP channel) is associated with increased risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms responsible. To avoid confounding effects of hyperglycemia, insulin secretion and action were studied in subjects with the variant who had normal glucose tolerance. RESEARCH DESIGN AND METHODS Nine subjects with the E23K genotype K/K and nine matched subjects with the E/E genotype underwent 5-h oral glucose tolerance tests (OGTTs), graded glucose infusion, and hyperinsulinemic-euglycemic clamp with stable-isotope–labeled tracer infusions to assess insulin secretion, action, and clearance. A total of 461 volunteers consecutively genotyped for the E23K variant also underwent OGTTs. Functional studies of the wild-type and E23K variant potassium channels were conducted. RESULTS Insulin secretory responses to oral and intravenous glucose were reduced by ∼40% in glucose-tolerant subjects homozygous for E23K. Normal glucose tolerance with reduced insulin secretion suggests a change in insulin sensitivity. The hyperinsulinemic-euglycemic clamp revealed that hepatic insulin sensitivity is ∼40% greater in subjects with the E23K variant, and these subjects demonstrate increased insulin sensitivity after oral glucose. The reconstituted E23K channels confirm reduced sensitivity to inhibitory ATP and increase in open probability, a direct molecular explanation for reduced insulin secretion. CONCLUSIONS The E23K variant leads to overactivity of the KATP channel, resulting in reduced insulin secretion. Initially, insulin sensitivity is enhanced, thereby maintaining normal glucose tolerance. Presumably, over time, as insulin secretion falls further or insulin resistance develops, glucose levels rise resulting in type 2 diabetes. PMID:19491206

Glucose metabolism and gene expression in juvenile zebrafish (Danio rerio) challenged with a high carbohydrate diet: effects of an acute glucose stimulus during late embryonic life.

PubMed

Rocha, Filipa; Dias, Jorge; Engrola, Sofia; Gavaia, Paulo; Geurden, Inge; Dinis, Maria Teresa; Panserat, Stephane

2015-02-14

Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 M) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP-6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [¹⁴C]glucose tracer; fish previously exposed to the stimulus showed lower retention of [¹⁴C]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles.

Quantification of β-cell insulin secretory function using a graded glucose infusion with C-peptide deconvolution in dysmetabolic, and diabetic cynomolgus monkeys.

PubMed

Wang, Xiaoli; Hansen, Barbara C; Shi, Da; Fang, Yupeng; Du, Fenglai; Wang, Bingdi; Chen, Yaxiong Michael; Gregoire, Francine M; Wang, Yi-Xin Jim

2013-07-25

Quantitation of β-cell function is critical in better understanding of the dynamic interactions of insulin secretion, clearance and action at different phases in the progression of diabetes. The present study aimed to quantify β-cell secretory function independently of insulin sensitivity in the context of differential metabolic clearance rates of insulin (MCRI) in nonhuman primates (NHPs). Insulin secretion rate (ISR) was derived from deconvolution of serial C-peptide concentrations measured during a 5 stage graded glucose infusion (GGI) in 12 nondiabetic (N), 8 prediabetic or dysmetabolic (DYS) and 4 overtly diabetic (DM) cynomolgus monkeys. The characterization of the monkeys was based on the fasting glucose and insulin concentrations, glucose clearance rate measured by intravenous glucose tolerance test, and insulin resistance indices measured in separate experiments. The molar ratio of C-peptide/insulin (C/I) was used as a surrogate index of hepatic MCRI. Compared to the N monkeys, the DYS with normal glycemia and hyperinsulinemia had significantly higher basal and GGI-induced elevation of insulin and C-peptide concentrations and lower C/I, however, each unit of glucose-stimulated ISR increment was not significantly different from that in the N monkeys. In contrast, the DM monkeys with β-cell failure and hyperglycemia had a depressed GGI-stimulated ISR response and elevated C/I. The present data demonstrated that in addition to β-cell hypersecretion of insulin, reduced hepatic MCRI may also contribute to the development of hyperinsulinemia in the DYS monkeys. On the other hand, hyperinsulinemia may cause the saturation of hepatic insulin extraction capacity, which in turn reduced MCRI in the DYS monkeys. The differential contribution of ISR and MCRI in causing hyperinsulinemia provides a new insight into the trajectory of β-cell dysfunction in the development of diabetes. The present study was the first to use the GGI and C-peptide deconvolution method to quantify the β-cell function in NHPs.

A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults.

PubMed

Vikøren, Linn A; Nygård, Ottar K; Lied, Einar; Rostrup, Espen; Gudbrandsen, Oddrun A

2013-02-28

The popularity of high-protein diets for weight reduction is immense. However, the potential benefits from altering the source of dietary protein rather than the amount is scarcely investigated. In the present study, we examined the effects of fish protein supplement on glucose and lipid metabolism in overweight adults. A total of thirty-four overweight adults were randomised to 8 weeks' supplementation with fish protein or placebo tablets (controls). The intake of fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4 weeks. In this study, 8 weeks of fish protein supplementation resulted in lower values of fasting glucose (P< 0·05), 2 h postprandial glucose (P< 0·05) and glucose-area under the curve (AUC) (five measurements over 2 h, P< 0·05) after fish protein supplementation compared to controls. Glucose-AUC was decreased after 8 weeks with fish protein supplement compared to baseline (P< 0·05), concomitant with increased 30 min and decreased 90 min and 2 h insulin C-peptide level (P< 0·05), and reduced LDL-cholesterol (P< 0·05). Body muscle % was increased (P< 0·05) and body fat % was reduced (P< 0·05) after 4 weeks' supplementation. Physical activity and energy and macronutrients intake did not change during the course of the study. In conclusion, short-term daily supplementation with a low dose of fish protein may have beneficial effects on blood levels of glucose and LDL-cholesterol as well as glucose tolerance and body composition in overweight adults. The long-term effects of fish protein supplementation is of interest in the context of using more fish as a protein source in the diet, and the effects of inclusion of fish in the diet of individuals with low glucose tolerance should be evaluated.

Prevention of hypoglycemia using risk assessment with a continuous glucose monitoring system.

PubMed

Choleau, Carine; Dokladal, Petr; Klein, Jean-Claude; Ward, W Kenneth; Wilson, George S; Reach, Gérard

2002-11-01

Due to the lag between sugar intake and the beginning of recovery from hypoglycemia, it is necessary to intervene in an anticipatory way if one wants to prevent, not only detect, hypoglycemia. This article presents the principle of a hypoglycemia prevention system based on risk assessment. The risk situation can be defined as the moment when the system estimates that the glucose concentration is expected to reach a hypoglycemia threshold in less than a given time (e.g., 20 min). Since there are well-known discrepancies between blood and interstitial glucose concentrations, the aim of this experimental study performed in nondiabetic rats was first to validate this strategy, and second to determine whether it can work when the glucose concentration is estimated by a glucose sensor in subcutaneous tissue rather than in blood. We used a model of controlled decrease in blood glucose concentration. A glucose infusion, the profile of which mimicked the appearance of glucose from an intragastric load, was administered either when hypoglycemia was detected or on the basis of risk recognition. Despite the lag between the beginning of the load and that of the increase in blood glucose concentration, which was in all experiments 15-20 min, hypoglycemia was fully prevented without overshoot hyperglycemia in the groups of rats in which the glucose load was started when the hypoglycemia risk was detected, on the basis of either blood or interstitial glucose concentration. This was, of course, not the case when the same glucose load was infused at the detection of the hypoglycemia threshold.

Effect of sulfonylureas administered centrally on the blood glucose level in immobilization stress model.

PubMed

Sharma, Naveen; Sim, Yun-Beom; Park, Soo-Hyun; Lim, Su-Min; Kim, Sung-Su; Jung, Jun-Sub; Hong, Jae-Seung; Suh, Hong-Won

2015-05-01

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

Development of an enzyme free glucose sensor based on copper oxide-graphene composite by using green reducing agent ascorbic acid

NASA Astrophysics Data System (ADS)

Palve, Yogesh Pandit; Jha, Neetu

2018-05-01

In this research work we have developed high sensitive and selective glucose sensor based on copper oxide-graphene composite which is prepared by green synthesis method and used for nonenzymatic glucose sensor. In present paper we report that present method highly selective, simple, efficient, accurate, ecofriendly, less toxic. The prepared composite were characterized by material characterization like SEM, XRD and also by electrochemical characterization like CV, chronoamperometry represents that copper oxide-graphene shows excellent electrocatalytic activity towards glucose, exhibiting a good sensitivity of 103.84 µA mM-1 cm-2, a fast response time 2s, a low detection limit 0.00033µM and linear range from 10 µM-3000 µM. The present sensor can successfully apply for determination of glucose concentration in human blood sample.

High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Wei; Department of Endocrinology, The People’s Hospital of Xindu, Xindu, Sichuang, 610500; Xu, Ling

Highlights: •The expression of SUMO1, SUMO2/3 under high glucose was obviously enhanced. •High glucose induced degradation of IκBα and activation of NF-κB pathway. •Sumoylation of IκBα in high glucose were significantly decreased. •The proteasome inhibitor MG132 could partially revert the degradation of IκBα. -- Abstract: The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation ofmore » inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p < 0.05). However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p < 0.05). The present results support the hypothesis that high glucose may activate NF-κB inflammatory signaling through IκBα sumoylation and ubiquitination.« less

Ameliorating effect of Semecarpus anacardium Linn. nut milk extract on altered glucose metabolism in high fat diet STZ induced type 2 diabetic rats.

PubMed

Khan, Haseena Banu Hedayathullah; Vinayagam, Kaladevi Siddhi; Palanivelu, Shanthi; Panchanadham, Sachdanandam

2012-12-01

To explore the protective effect of the drug Semecarpus anacardium (S. anacardium)on altered glucose metabolism in diabetic rats. Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ) (35 mg/kg b.w.). Seven days after STZ induction, diabetic rats received nut milk extract of S. anacardium Linn. nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks. The effect of nut milk extract of S. anacardium on blood glucose, plasma insulin, glucose metabolising enzymes and GSK were studied. Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA - β and decrease in HOMA -IR. The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes. The drug also effectively ameliorated the alterations in GSK-3 mRNA expression. Overall, the present study demonstrates the possible mechanism of glucose regulation of S. anacardium suggestive of its therapeutic potential for the management of diabetes mellitus. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial.

PubMed

Osei, Elizabeth; Fonville, Susanne; Zandbergen, Adrienne A M; Brouwers, Paul J A M; Mulder, Laus J M M; Lingsma, Hester F; Dippel, Diederik W J; Koudstaal, Peter J; den Hertog, Heleen M

2015-08-05

Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months. This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance. NTR3196 , Date of registration: 15 December 2011.

Mesenteric blood flow, glucose absorption and blood pressure responses to small intestinal glucose in critically ill patients older than 65 years.

PubMed

Sim, Jennifer A; Horowitz, M; Summers, M J; Trahair, L G; Goud, R S; Zaknic, A V; Hausken, T; Fraser, J D; Chapman, M J; Jones, K L; Deane, A M

2013-02-01

To compare nutrient-stimulated changes in superior mesenteric artery (SMA) blood flow, glucose absorption and glycaemia in individuals older than 65 years with, and without, critical illness. Following a 1-h 'observation' period (t (0)-t (60)), 0.9 % saline and glucose (1 kcal/ml) were infused directly into the small intestine at 2 ml/min between t (60)-t (120), and t (120)-t (180), respectively. SMA blood flow was measured using Doppler ultrasonography at t (60) (fasting), t (90) and t (150) and is presented as raw values and nutrient-stimulated increment from baseline (Δ). Glucose absorption was evaluated using serum 3-O-methylglucose (3-OMG) concentrations during, and for 1 h after, the glucose infusion (i.e. t (120)-t (180) and t (120)-t (240)). Mean arterial pressure was recorded between t (60)-t (240). Data are presented as median (25th, 75th percentile). Eleven mechanically ventilated critically ill patients [age 75 (69, 79) years] and nine healthy volunteers [70 (68, 77) years] were studied. The magnitude of the nutrient-stimulated increase in SMA flow was markedly less in the critically ill when compared with healthy subjects [Δt (150): patients 115 (-138, 367) versus health 836 (618, 1,054) ml/min; P = 0.001]. In patients, glucose absorption was reduced during, and for 1 h after, the glucose infusion when compared with health [AUC(120-180): 4.571 (2.591, 6.551) versus 11.307 (8.447, 14.167) mmol/l min; P < 0.001 and AUC(120-240): 26.5 (17.7, 35.3) versus 40.6 (31.7, 49.4) mmol/l min; P = 0.031]. A close relationship between the nutrient-stimulated increment in SMA flow and glucose absorption was evident (3-OMG AUC(120-180) and ∆SMA flow at t (150): r (2) = 0.29; P < 0.05). In critically ill patients aged >65 years, stimulation of SMA flow by small intestinal glucose infusion may be attenuated, which could account for the reduction in glucose absorption.

Glucose Biosensors: An Overview of Use in Clinical Practice

PubMed Central

Yoo, Eun-Hyung; Lee, Soo-Youn

2010-01-01

Blood glucose monitoring has been established as a valuable tool in the management of diabetes. Since maintaining normal blood glucose levels is recommended, a series of suitable glucose biosensors have been developed. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. This article reviews the brief history, basic principles, analytical performance, and the present status of glucose biosensors in the clinical practice. PMID:22399892

Positive Allosteric Modulation of the Calcium-sensing Receptor by Physiological Concentrations of Glucose*

PubMed Central

Medina, Johan; Nakagawa, Yuko; Nagasawa, Masahiro; Fernandez, Anny; Sakaguchi, Kazushige; Kitaguchi, Tetsuya; Kojima, Itaru

2016-01-01

The calcium-sensing receptor (CaSR) is activated by various cations, cationic compounds, and amino acids. In the present study we investigated the effect of glucose on CaSR in HEK293 cells stably expressing human CaSR (HEK-CaSR cells). When glucose concentration in the buffer was raised from 3 to 25 mm, a rapid elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) was observed. This elevation was immediate and transient and was followed by a sustained decrease in [Ca2+]c. The effect of glucose was detected at a concentration of 4 mm and reached its maximum at 5 mm. 3-O-Methylglucose, a non-metabolizable analogue of glucose, reproduced the effect of glucose. Sucrose also induced an elevation of [Ca2+]c in HEK-CaSR cells. Similarly, sucralose was nearly as effective as glucose in inducing elevation of [Ca2+]c. Glucose was not able to increase [Ca2+]c in the absence of extracellular Ca2+. The effect of glucose on [Ca2+]c was inhibited by NPS-2143, an allosteric inhibitor of CaSR. In addition, NPS-2143 also inhibited the [Ca2+]c responses to sucralose and sucrose. Glucose as well as sucralose decreased cytoplasmic cAMP concentration in HEK-CaSR cells. The reduction of cAMP induced by glucose was blocked by pertussis toxin. Likewise, sucralose reduced [cAMP]c. Finally, glucose increased [Ca2+]c in PT-r parathyroid cells and in Madin-Darby canine kidney cells, both of which express endogenous CaSR. These results indicate that glucose acts as a positive allosteric modulator of CaSR. PMID:27613866

Role of chrysin on expression of insulin signaling molecules

PubMed Central

Satyanarayana, Kottireddy; Sravanthi, Koora; Shaker, Ivvala Anand; Ponnulakshmi, Rajagopal; Selvaraj, Jayaraman

2015-01-01

Background: Currently available drugs are unsuccessful for the treatment of tye-2 diabetes due to their adverseside-effects. Hence, a search for novel drugs, especially ofplant origin, continues. Chrysin (5,7-dihydroxyflavone) is a flavonoid, natural component of traditional medicinal herbs, present in honey, propolis and many plant extracts that hasbeen used in traditional medicine around the world to treat numerous ailments. Objective: The present study was aimed to identify the protective role of chrysin on the expression of insulin-signaling molecules in the skeletal muscle of high fat and sucrose-induced type-2 diabetic adult male rats. Materials and Methods: The oral effective dose of chrysin (100 mg/kg body weight) was given once a day until the end of the study (30 days post-induction of diabetes) to high fat diet-induced diabetic rats. At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, lipid peroxidation (LPO) and free radical generation, as well as the levels of insulin signaling molecules and tissue glycogen in the gastrocnemius muscle were assessed. Results: Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (IR, IRS-1, p-IRS-1Tyr632, p- AktThr308), glucose transporter subtype 4 [GLUT4] proteins and glycogen concentration. Serum insulin, lipid profile, LPO and free radical generation were found to be increased in diabetic control rats. The treatment with chrysin normalized the altered levels of blood glucose, serum insulin, lipid profile, LPO and insulin signaling molecules as well as GLUT4 proteins. Conclusion: Our present findings indicate that chrysin improves glycemic control through activation of insulin signal transduction in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic male rats. PMID:26834424

A disposable tear glucose biosensor--part 3: assessment of enzymatic specificity.

PubMed

Lan, Kenneth; McAferty, Kenyon; Shah, Pankti; Lieberman, Erica; Patel, Dharmendra R; Cook, Curtiss B; La Belle, Jeffrey T

2011-09-01

A concept for a tear glucose sensor based on amperometric measurement of enzymatic oxidation of glucose was previously presented, using glucose dehydrogenase flavin adenine dinucleotide (GDH-FAD) as the enzyme. Glucose dehydrogenase flavin adenine dinucleotide is further characterized in this article and evaluated for suitability in glucose-sensing applications in purified tear-like saline, with specific attention to the effect of interfering substances only. These interferents are specifically saccharides that could interact with the enzymatic activity seen in the sensor's performance. Bench top amperometric glucose assays were performed using an assay solution of GDH-FAD and ferricyanide redox mediator with samples of glucose, mannose, lactose, maltose, galactose, fructose, sucrose, and xylose at varying concentrations to evaluate specificity, linear dynamic range, signal size, and signal-to-noise ratio. A comparison study was done by substituting an equivalent activity unit concentration of glucose oxidase (GOx) for GDH-FAD. Glucose dehydrogenase flavin adenine dinucleotide was found to be more sensitive than GOx, producing larger oxidation currents than GOx on an identical glucose concentration gradient, and GDH-FAD exhibited larger slope response (-5.65 × 10(-7) versus -3.11 × 10(-7) A/mM), signal-to-noise ratio (18.04 versus 2.62), and linear dynamic range (0-30 versus 0-10 mM), and lower background signal (-7.12 versus -261.63 nA) than GOx under the same assay conditions. GDH-FAD responds equally to glucose and xylose but is otherwise specific for glucose. Glucose dehydrogenase flavin adenine dinucleotide compares favorably with GOx in many sensor-relevant attributes and may enable measurement of glucose concentrations both higher and lower than those measurable by GOx. GDH-FAD is a viable enzyme to use in the proposed amperometric tear glucose sensor system and perhaps also in detecting extreme hypoglycemia or hyperglycemia in blood. © 2011 Diabetes Technology Society.

A Disposable Tear Glucose Biosensor—Part 3: Assessment of Enzymatic Specificity

PubMed Central

Lan, Kenneth; McAferty, Kenyon; Shah, Pankti; Lieberman, Erica; Patel, Dharmendra R; Cook, Curtiss B; La Belle, Jeffrey T

2011-01-01

Background A concept for a tear glucose sensor based on amperometric measurement of enzymatic oxidation of glucose was previously presented, using glucose dehydrogenase flavin adenine dinucleotide (GDH-FAD) as the enzyme. Glucose dehydrogenase flavin adenine dinucleotide is further characterized in this article and evaluated for suitability in glucose-sensing applications in purified tear-like saline, with specific attention to the effect of interfering substances only. These interferents are specifically saccharides that could interact with the enzymatic activity seen in the sensor's performance. Methods Bench top amperometric glucose assays were performed using an assay solution of GDH-FAD and ferricyanide redox mediator with samples of glucose, mannose, lactose, maltose, galactose, fructose, sucrose, and xylose at varying concentrations to evaluate specificity, linear dynamic range, signal size, and signal-to-noise ratio. A comparison study was done by substituting an equivalent activity unit concentration of glucose oxidase (GOx) for GDH-FAD. Results Glucose dehydrogenase flavin adenine dinucleotide was found to be more sensitive than GOx, producing larger oxidation currents than GOx on an identical glucose concentration gradient, and GDH-FAD exhibited larger slope response (-5.65 × 10-7 versus -3.11 × 10-7 A/mM), signal-to-noise ratio (18.04 versus 2.62), and linear dynamic range (0–30 versus 0–10 mM), and lower background signal (-7.12 versus -261.63 nA) than GOx under the same assay conditions. GDH-FAD responds equally to glucose and xylose but is otherwise specific for glucose. Conclusion Glucose dehydrogenase flavin adenine dinucleotide compares favorably with GOx in many sensor-relevant attributes and may enable measurement of glucose concentrations both higher and lower than those measurable by GOx. GDH-FAD is a viable enzyme to use in the proposed amperometric tear glucose sensor system and perhaps also in detecting extreme hypoglycemia or hyperglycemia in blood. PMID:22027303

Effect of a Prolonged Altitude Expedition on Glucose Tolerance and Abdominal Fatness

ERIC Educational Resources Information Center

Chen, Mu-Tsung; Lee, Wen-Chih; Chen, Shih-Chang; Chen, Chiu-Chou; Chen, Chung-Yu; Lee, Shin-Da; Jensen, Jorgen; Kuo, Chia-Hua

2010-01-01

In the present study, we investigated the effect of a long-term mountain expedition on glucose tolerance and insulin action. Twelve registered mountaineers ages 31 years (SD = 1.1) participated in a 25-day expedition at a 2,200-3,800-m altitude with an average duration of 8 hr per day. Arterial oxygen saturation (SaO[subscript 2]) was…

Screening of medicinal plants for PPPAR-alpha and PPAR-gamma activation and evaluation of their effects on glucose uptake and 3T3-L1 adipogenesis

USDA-ARS?s Scientific Manuscript database

Medicinal plants are a rich source of ligands for nuclear receptors. The present study was aimed to screen a collection of plant extracts for PPAR-alpha/gamma activating properties and identify the active extract that can stimulate cellular glucose uptake without enhancing the adipogenesis. A report...

Orosomucoid binds insulin and IGF1 and reduces hormone stimulated protein synthesis and glucose metabolism in C2C12 myotubes

USDA-ARS?s Scientific Manuscript database

Previous research has indicated that orosomuciod (ORM1) may enhance insulin response in 3T3-L1 adipocytes. The present study was undertaken to determine if ORM1 can modify muscle metabolism by examining glucose oxidation and protein synthesis in the C2C12 muscle cell line. Cells were used for expe...

Detection of saliva-range glucose concentrations using organic thin-film transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elkington, D.; Belcher, W. J.; Dastoor, P. C.

We describe the development of a glucose sensor through direct incorporation of an enzyme (glucose oxidase) into the gate of an organic thin film transistor (OTFT). We show that glucose diffusion is the key determinant of the device response time and present a mechanism of glucose sensing in these devices that involves protonic doping of the transistor channel via enzymatic oxidation of glucose. The integrated OTFT sensor is sensitive across 4 decades of glucose concentration; a range that encompasses both the blood and salivary glucose concentration levels. As such, this work acts as a proof-of-concept for low-cost printed biosensors formore » salivary glucose.« less

Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition

PubMed Central

Zukerman, Steven; Ackroff, Karen

2014-01-01

Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS−) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward. PMID:25320345

The impact of blood glucose levels on stimulated adrenocorticotropin hormone and growth hormone release in healthy subjects.

PubMed

Jakobsdóttir, S; Twisk, J W R; Drent, M L

2009-12-01

In studies investigating the influence of glucose levels on the pituitary function the methods used have been variable and mainly focused on the change in function as a reaction to unphysiological low or high blood glucose levels. In the present study the impact of physiological and elevated blood glucose levels on adrenocorticotropin hormone (ACTH) and growth hormone release are investigated. The euglycaemic and hyperglycaemic clamp techniques were used to reach stable levels of 4, 8 and 12 mmol/l blood glucose levels. After a stabilization phase of 2 h, a corticotropin releasing hormone (CRH) or a growth hormone releasing hormone (GHRH) stimulation test was performed. Seven and eight healthy male volunteers, belonging to two groups, participated in this study. The area under the curve (AUC), peak values and time to peak of ACTH, cortisol and growth hormone were calculated to evaluate the response to the CRH and GHRH stimulation test. The peak values of ACTH, cortisol and growth hormone seemed to be the highest during the 4 mmol/l clamp sessions, compared with the 8 and 12 mmol/l clamps, although the differences were not statistically significant when analysed for every subject individually. The AUC and time to peak measurements were comparable during the three clamp procedures. The pituitary reaction on CRH and GHRH was not significantly changed by various blood glucose levels. © 2009 Blackwell Publishing Ltd.

Measurement of cerebral oxidative glucose consumption in patients with type 1 diabetes and hypoglycemia unawareness using 13C nuclear magnetic resonance spectroscopy

PubMed Central

Henry, Pierre-Gilles; Criego, Amy B.; Kumar, Anjali; Seaquist, Elizabeth R.

2009-01-01

The aim of the present study was to use 13C NMR to measure the cerebral oxidative metabolic rate of glucose (CMRglc(ox)) in patients with diabetes and to compare these measurements with those collected from matched controls. We elected to study a group with type 1 diabetes and hypoglycemia unawareness, since we had previously found such patients to have higher brain glucose concentrations than normal volunteers under steady state conditions. We sought to determine if this difference in steady-state brain concentrations could be explained by a difference in CMRglc(ox). Time courses of 13C label incorporation in brain amino acids were measured in occipital cortex during infusion of [1-13C]glucose. These time courses were fitted using a one-compartment metabolic model to determine CMRglc(ox). Our results show that the TCA cycle rate (VTCA, which is twice CMRglc(ox)) in subjects with type 1 diabetes was not significantly different from normal controls (0.84 ± 0.03 vs 0.79 ± 0.03 μmol/gm/min, n=5 in each group, mean ± SEM). We conclude that the changes in steady-state brain glucose concentrations that we observed in patients with type 1 diabetes in a previous study (1) cannot be explained by changes in oxidative glucose consumption PMID:19766263

Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition.

PubMed

Sclafani, Anthony; Zukerman, Steven; Ackroff, Karen

2014-12-15

Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS-) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward. Copyright © 2014 the American Physiological Society.

Application of the integrated glucose–insulin model for cross‐study characterization of T2DM patients on metformin background treatment

PubMed Central

Hamrén, Bengt; Kjellsson, Maria C.; Skrtic, Stanko

2016-01-01

Aim The integrated glucose–insulin (IGI) model is a semi‐mechanistic physiological model which can describe the glucose–insulin homeostasis system following various glucose challenge settings. The aim of the present work was to apply the model to a large and diverse population of metformin‐only‐treated type 2 diabetes mellitus (T2DM) patients and identify patient‐specific covariates. Methods Data from four clinical studies were pooled, including glucose and insulin concentration–time profiles from T2DM patients on stable treatment with metformin alone following mixed‐meal tolerance tests. The data were collected from a wide range of patients with respect to the duration of diabetes and level of glycaemic control. Results The IGI model was expanded by four patient‐specific covariates. The level of glycaemic control, represented by baseline glycosylated haemoglobin was identified as a significant covariate for steady‐state glucose, insulin‐dependent glucose clearance and the magnitude of the incretin effect, while baseline body mass index was a significant covariate for steady‐state insulin levels. In addition, glucose dose was found to have an impact on glucose absorption rate. The developed model was used to simulate glucose and insulin profiles in different groups of T2DM patients, across a range of glycaemic control, and it was found accurately to characterize their response to the standard oral glucose challenge. Conclusions The IGI model was successfully applied to characterize differences between T2DM patients across a wide range of glycaemic control. The addition of patient‐specific covariates in the IGI model might be valuable for the future development of antidiabetic treatment and for the design and simulation of clinical studies. PMID:27450071

Variants of transcription factor 7-like 2 (TCF7L2) gene and incident glucose intolerance in Japanese-Brazilians.

PubMed

Franco, L F; Crispim, F; Pereira, A C; Moisés, R S

2011-03-01

Common variants of the transcription factor 7-like 2 (TCF7L2) gene have been found to be associated with type 2 diabetes in different ethnic groups. The Japanese-Brazilian population has one of the highest prevalence rates of diabetes. Therefore, the aim of the present study was to assess whether two single-nucleotide polymorphisms (SNPs) of TCF7L2, rs7903146 and rs12255372, could predict the development of glucose intolerance in Japanese-Brazilians. In a population-based 7-year prospective study, we genotyped 222 individuals (72 males and 150 females, aged 56.2 ± 10.5 years) with normal glucose tolerance at baseline. In the study population, we found that the minor allele frequency was 0.05 for SNP rs7903146 and 0.03 for SNP rs12255372. No significant allele or genotype association with glucose intolerance incidence was found for either SNP. Haplotypes were constructed with these two SNPs and three haplotypes were defined: CG (frequency: 0.94), TT (frequency = 0.027) and TG (frequency = 0.026). None of the haplotypes provided evidence for association with the incidence of glucose intolerance. Despite no associations between incidence of glucose intolerance and SNPs of the TCF7L2 gene in Japanese-Brazilians, we found that carriers of the CT genotype for rs7903146 had significantly lower insulin levels 2 h after a 75-g glucose load than carriers of the CC genotype. In conclusion, in Japanese-Brazilians, a population with a high prevalence of type 2 diabetes, common TCF7L2 variants did not make major contributions to the incidence of glucose tolerance abnormalities.

Diurnal pattern to insulin secretion and insulin action in healthy individuals.

PubMed

Saad, Ahmed; Dalla Man, Chiara; Nandy, Debashis K; Levine, James A; Bharucha, Adil E; Rizza, Robert A; Basu, Rita; Carter, Rickey E; Cobelli, Claudio; Kudva, Yogish C; Basu, Ananda

2012-11-01

Evaluation of the existence of a diurnal pattern of glucose tolerance after mixed meals is important to inform a closed-loop system of treatment for insulin requiring diabetes. We studied 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA(1c) (5.2 ± 0.0%) to determine such a pattern in nondiabetic individuals. Identical mixed meals were ingested during breakfast, lunch, or dinner at 0700, 1300, and 1900 h in randomized Latin square order on 3 consecutive days. Physical activity was the same on all days. Postprandial glucose turnover was measured using the triple tracer technique. Postprandial glucose excursion was significantly lower (P < 0.01) at breakfast than lunch and dinner. β-Cell responsivity to glucose and disposition index was higher (P < 0.01) at breakfast than lunch and dinner. Hepatic insulin extraction was lower (P < 0.01) at breakfast than dinner. Although meal glucose appearance did not differ between meals, suppression of endogenous glucose production tended to be lower (P < 0.01) and insulin sensitivity tended to be higher (P < 0.01) at breakfast than at lunch or dinner. Our results suggest a diurnal pattern to glucose tolerance in healthy humans, and if present in type 1 diabetes, it will need to be incorporated into artificial pancreas systems.

Optical coherence tomography for blood glucose monitoring in vitro through spatial and temporal approaches

NASA Astrophysics Data System (ADS)

De Pretto, Lucas Ramos; Yoshimura, Tania Mateus; Ribeiro, Martha Simões; Zanardi de Freitas, Anderson

2016-08-01

As diabetes causes millions of deaths worldwide every year, new methods for blood glucose monitoring are in demand. Noninvasive approaches may increase patient adherence to treatment while reducing costs, and optical coherence tomography (OCT) may be a feasible alternative to current invasive diagnostics. This study presents two methods for blood sugar monitoring with OCT in vitro. The first, based on spatial statistics, exploits changes in the light total attenuation coefficient caused by different concentrations of glucose in the sample using a 930-nm commercial OCT system. The second, based on temporal analysis, calculates differences in the decorrelation time of the speckle pattern in the OCT signal due to blood viscosity variations with the addition of glucose with data acquired by a custom built Swept Source 1325-nm OCT system. Samples consisted of heparinized mouse blood, phosphate buffer saline, and glucose. Additionally, further samples were prepared by diluting mouse blood with isotonic saline solution to verify the effect of higher multiple scattering components on the ability of the methods to differentiate glucose levels. Our results suggest a direct relationship between glucose concentration and both decorrelation rate and attenuation coefficient, with our systems being able to detect changes of 65 mg/dL in glucose concentration.

Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4.

PubMed

Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V; Manjunath, Kirangadur; Viswanatha, Gollapalle L; Ashok, Godavarthi

2014-12-01

The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria (MFMC) on PPARγ (Peroxisome Proliferator Activated Receptor gamma) and GLUT-4 (Glucose transporter-4) with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL(-1) were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC (500 μg·mL(-1)) was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARγ gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide (CHX), which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARγ and GLUT-4 in vitro. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Low glucose level and low pH alter the electrochemical function of human parietal pleura.

PubMed

Kouritas, V K; Hatzoglou, C; Foroulis, C N; Hevas, A; Gourgoulianis, K I; Molyvdas, P A

2007-08-01

The aim of the present study was to investigate whether low glucose and pH level, which are usually measured in complicated pleural effusions, alter the electrochemical function of healthy human parietal pleura. Parietal pleural pieces were stripped from 66 patients during thoracic surgery and were mounted in Ussing chambers. Krebs' solutions containing different glucose levels (0, 40 and 100 mg) and balanced at different pH levels (7.4, 7.3 and 7.2) were added to the pleural cavity surface of the pieces. Transmesothelial potential difference was measured at various time-points as an electrophysiological variable and transmesothelial resistance (R(TM)) was calculated using Ohm's law. When normal-glucose Krebs at pH 7.45 was used, R(TM) remained unchanged over time, but when low-glucose Krebs was used, R(TM) decreased. Krebs without glucose caused the greatest decrease in R(TM). Use of low-pH Krebs decreased R(TM). The lower the pH of the Krebs, the faster the decrease in R(TM) and the greater the effect. The decrease in R(TM) was greater with low-pH than with low-glucose Krebs. Low glucose and low pH caused an additive decrease in R(TM). Low glucose concentration and low pH cause alteration of the electrochemical function of human parietal pleura and could act as agents that lead to further exudate progression.

Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.

PubMed

Jabbour, S A; Goldstein, B J

2008-08-01

The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR.

PubMed

Han, Liang; Ma, Qingyong; Li, Junhui; Liu, Han; Li, Wei; Ma, Guodong; Xu, Qinhong; Zhou, Shuang; Wu, Erxi

2011-01-01

Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration-dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time-dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia.

Effects of Red Wine Tannat on Oxidative Stress Induced by Glucose and Fructose in Erythrocytes in Vitro

PubMed Central

Pazzini, Camila Eliza Fernandes; Colpo, Ana Ceolin; Poetini, Márcia Rósula; Pires, Cauê Ferreira; de Camargo, Vanessa Brum; Mendez, Andreas Sebastian Loureiro; Azevedo, Miriane Lucas; Soares, Júlio César Mendes; Folmer, Vanderlei

2015-01-01

The literature indicates that red wine presents in its composition several substances that are beneficial to health. This study has investigated the antioxidant effects of Tannat red wine on oxidative stress induced by glucose and fructose in erythrocytes in vitro, with the purpose to determine some of its majoritarian phenolic compounds and its antioxidant capacity. Erythrocytes were incubated using different concentrations of glucose and fructose in the presence or absence of wine. From these erythrocytes were determined the production of thiobarbituric acid reactive species (TBARS), glucose consumption, and osmotic fragility. Moreover, quantification of total phenolic, gallic acid, caffeic acid, epicatechin, resveratrol, and DPPH scavenging activity in wine were also assessed. Red wine showed high levels of polyphenols analyzed, as well as high antioxidant potential. Erythrocytes incubated with glucose and fructose had an increase in lipid peroxidation and this was prevented by the addition of wine. The wine increased glucose uptake into erythrocytes and was able to decrease the osmotic fragility of erythrocytes incubated with fructose. Altogether, these results suggest that wine leads to a reduction of the oxidative stress induced by high concentrations of glucose and fructose. PMID:26078708

Astrocyte glycogen as an emergency fuel under conditions of glucose deprivation or intense neural activity.

PubMed

Brown, Angus M; Ransom, Bruce R

2015-02-01

Energy metabolism in the brain is a complex process that is incompletely understood. Although glucose is agreed as the main energy support of the brain, the role of glucose is not clear, which has led to controversies that can be summarized as follows: the fate of glucose, once it enters the brain is unclear. It is not known the form in which glucose enters the cells (neurons and glia) within the brain, nor the degree of metabolic shuttling of glucose derived metabolites between cells, with a key limitation in our knowledge being the extent of oxidative metabolism, and how increased tissue activity alters this. Glycogen is present within the brain and is derived from glucose. Glycogen is stored in astrocytes and acts to provide short-term delivery of substrates to neural elements, although it may also contribute an important component to astrocyte metabolism. The roles played by glycogen awaits further study, but to date its most important role is in supporting neural elements during increased firing activity, where signaling molecules, proposed to be elevated interstitial K(+), indicative of elevated neural firing rates, activate glycogen phosphorylase leading to increased production of glycogen derived substrate.

Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur

PubMed Central

Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

2015-01-01

Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months’ supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze.jlr Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. PMID:26063461

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

PubMed

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2016-01-01

Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Gemfibrozil not fenofibrate decreases systemic glucose level via PPARα.

PubMed

Song, Danjun; Chu, Zanbo; Min, Luo; Zhen, Tan; Li, Pengxu; Han, Liyuan; Bu, Shizhong; yang, Julin; Gonzale, F J; Liu, Aiming

2016-04-01

Concurrence of high glucose or diabetes in patients with dyslipidemia is presenting major challenges for clinicians. Although sporadically reported, a rational basis for the use of fibrates for the treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type (WT) and Ppara-null (KO) mice were fed a serial gemfibrozil- and fenofibrate-containing diet under the same experimental conditions for 14 days. Glucose level in the blood, glycogen storage in the liver tissues, and the potential toxic responses were assayed. Genes involved in glucose metabolism were determined by quantitative polymerase chain reaction analysis. Both the blood glucose level and the glycogen content in the liver were down-regulated by gemfibrozil but not by fenofibrate in WT mice, in a dose-dependent manner. This decrement did not occur in KO mice for either fibrate agent. Secondary regulation on the transcription of pyruvate kinase, and gluconolactonase were observed following gemfibrozil treatment, which was differential between WT mice and KO mice. Gemfibrozil, not fenofibrate, down-regulates systemic glucose level and glycogen storage in the liver dependent on PPARα, suggesting its potential value for treatment of dyslipidemia with concurrent diabetes or high glucose levels.

Hyper-G stress-induced hyperglycemia in rats mediated by glucoregulatory hormones

NASA Technical Reports Server (NTRS)

Daligcon, B. C.; Oyama, J.

1985-01-01

The present investigation is concerned with possible relations of the hyperglycemic response of rats exposed to hyper-G stress to (1) alterations in blood levels of the glucoregulatory hormones and gluconeogenic substrates, and (2) changes in insulin response on muscle glucose uptake. Male Sprague-Dawley rats weighing 250-300 g were used in the study. The results of the experiments indicate that the initial rapid rise in blood glucose of rats exposed to hyper-G stress is mediated by increases in circulating catecholamines and glucagon, both potent stimulators of hepatic gluconeogenesis. Lactate, derived from epinephrine stimulation of muscle glycogenolysis, appears to be a major precursor for the initial rise in blood glucose. The inhibition of the insulin-stimulated glucose uptake by muscle tissues may be a factor in the observed sustained hyperglycemia.

Digital Photography as an Educational Food Logging Tool in Obese Patients with Type 2 Diabetes: Lessons Learned from A Randomized, Crossover Pilot Trial

PubMed Central

Ehrmann, Brett J.; Anderson, Robert M.; Piatt, Gretchen A.; Funnell, Martha M.; Rashid, Hira; Shedden, Kerby; Douyon, Liselle

2014-01-01

Purpose The purpose of this pilot study is to investigate the utility of, and areas of refinement for, digital photography as an educational tool for food logging in obese patients with type 2 diabetes (T2DM). Methods Thirty-three patients aged 18-70 with T2DM, BMI at least 30 kg/m2, and A1C 7.5-9% were recruited from an endocrinology clinic and randomized to a week of food logging using a digital camera (DC) or paper diary (PD), crossing over for week two. Patients then viewed a presentation about dietary effects on blood glucose, using patient DC and blood glucose entries. Outcomes of adherence (based on number of weekly entries), changes in mean blood glucose and frequency of blood glucose checks, and patient satisfaction were compared between methods. Patient feedback on the DC intervention and presentation was also analyzed. Results Thirty patients completed the study. Adherence was identical across methods. The mean difference in number of entries was not significant between methods. This difference increased and neared statistical significance (favoring DC) among patients who were adherent for at least one week (21 entries, with 2 entries per day for 5 of 7 days, n=25). Mean blood glucose did not significantly decrease in either method. Patient satisfaction was similar between interventions. Feedback indicated concerns over photograph accuracy, forgetting to use the cameras, and embarrassment using them in public. Conclusion Though comparable to PD in adherence, blood glucose changes, and patient satisfaction in this pilot trial, patient feedback suggested specific areas of refinement to maximize utility of DC-based food logging as an educational tool in T2DM. PMID:24168836

Controlling type 2 diabetes mellitus with herbal medicines: A triple-blind randomized clinical trial of efficacy and safety.

PubMed

Mirfeizi, Mani; Mehdizadeh Tourzani, Zahra; Mirfeizi, Seyedeh Zahra; Asghari Jafarabadi, Mohammad; Rezvani, Hamid Reza; Afzali, Monireh

2016-09-01

The use of alternative medicines is common in patients with diabetes mellitus. The primary aim of the present study was to determine the effects of cinnamon and Caucasian whortleberry (Vaccinium arctostaphylos L.) on blood glucose control, lipid profile and body mass index (BMI) in patients with type 2 diabetes (T2DM). In all, 105 T2DM patients were recruited to the present randomized triple-blinded clinical trial. Patients were randomly divided into three groups and administered either placebo, cinnamon or whortleberry supplements (1 g/day) for 90 days. Fasting blood glucose (FBG), serum insulin, lipid profiles, and HbA1c were measured before and after the study. There were no significant differences in baseline characteristics among the three groups. After treatment, FBG, 2-h blood postprandial glucose and homeostasis model assessment of insulin resistance (HOMA-IR) scores were significantly reduced in patients in the whortleberry group, but not in the placebo group. After treatment, there was a significant difference in BMI between the cinnamon and control groups (P = 0.02). There were no significant differences in any variables between the cinnamon and whortleberry groups (P>0.05 for all). In addition, there was a significant decrease in all indices of glucose control in all the cinnamon and whortleberry groups (P < 0.05). There were no significant differences in blood glucose levels, insulin sensitivity or lipid profile among the three groups. However, the use of cinnamon and whortleberry in addition to conventional medical treatment is recommended to adjust weight and blood glucose levels in patients with T2DM, respectively. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Continuous Glucose Monitoring (CGM) or Blood Glucose Monitoring (BGM): Interactions and Implications.

PubMed

Heinemann, Lutz

2018-04-01

At the 2017 10th annual International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) in Paris, France, four speakers presented their perspectives on the roles of continuous glucose monitoring (CGM) and of blood glucose monitoring (BGM) in patient management within one symposium. These presentations included discussions of the differences in the accuracy of CGM and BGM, a clinical perspective on the physiological reasons behind differences in CGM and BGM values, and an overview of the impact of variations in device accuracy on patients with diabetes. Subsequently a short summary of these presentations is given, highlighting the value of good accuracy of BGM or CGM systems and the ongoing need for standardization. The important role of both BGM and CGM in patient management was a theme across all presentations.

Investigating the Mechanisms Underlying Neuronal Death in Ischemia Using In Vitro Oxygen-Glucose Deprivation: Potential Involvement of Protein SUMOylation

PubMed Central

CIMAROSTI, HELENA; HENLEY, JEREMY M.

2012-01-01

It is well established that brain ischemia can cause neuronal death via different signaling cascades. The relative importance and interrelationships between these pathways, however, remain poorly understood. Here is presented an overview of studies using oxygen-glucose deprivation of organotypic hippocampal slice cultures to investigate the molecular mechanisms involved in ischemia. The culturing techniques, setup of the oxygen-glucose deprivation model, and analytical tools are reviewed. The authors focus on SUMOylation, a posttranslational protein modification that has recently been implicated in ischemia from whole animal studies as an example of how these powerful tools can be applied and could be of interest to investigate the molecular pathways underlying ischemic cell death. PMID:19029060

Interrelations between glucose-induced insulin response, metabolic indicators, and time of first ovulation in high-yielding dairy cows.

PubMed

Bossaert, P; Leroy, J L M R; De Vliegher, S; Opsomer, G

2008-09-01

High-yielding dairy cows are more susceptible to metabolic and reproductive disorders than low-yielding cows. Insulin plays a pivotal role in the development of both problems. In the present study, we aimed to assess the glucose-induced insulin responses of dairy cows at different time points relative to calving and to relate this to the metabolic status and the time of first ovulation. Twenty-three healthy, multiparous Holstein-Friesian cows with a high genetic merit for milk yield were studied from 14 d prepartum to 42 d postpartum. Intravenous glucose tolerance tests were performed on -14, 14, and 42 d relative to calving to evaluate the plasma insulin and glucose responses to a glucose load, as estimated by the peak concentration, the area under the curve (AUC), and the clearance rates of insulin and glucose. Blood samples were obtained at 3-d intervals and analyzed for glucose, insulin, and nonesterified fatty acids (NEFA). The time of first ovulation was defined by transrectal ultrasonography and plasma progesterone analysis. Glucose-induced insulin AUC and peak concentration decreased and glucose clearance increased during lactation compared with the dry period. Plasma NEFA concentrations were negatively related to insulin AUC and peak concentrations. Fourteen cows ovulated within 42 d postpartum, and the remaining 9 cows suffered from delayed resumption of ovarian function. Survival analysis demonstrated that cows with lower NEFA concentrations during the dry period tended to have earlier resumption of ovarian activity. In conclusion, our data suggest a decreased plasma insulin response to glucose postpartum in high-yielding dairy cows, possibly contributing to metabolic stress during the early postpartum period. It is hypothesized that NEFA impair glucose-induced insulin secretion in dairy cows. Additionally, our results suggest the importance of lipolysis during the transition period as a risk factor for delayed ovulation.

Brain Activation in Response to Personalized Behavioral and Physiological Feedback From Self-Monitoring Technology: Pilot Study

PubMed Central

Morgan, Paul S; Sherar, Lauren B; Kingsnorth, Andrew P; Magistro, Daniele; Esliger, Dale W

2017-01-01

Background The recent surge in commercially available wearable technology has allowed real-time self-monitoring of behavior (eg, physical activity) and physiology (eg, glucose levels). However, there is limited neuroimaging work (ie, functional magnetic resonance imaging [fMRI]) to identify how people’s brains respond to receiving this personalized health feedback and how this impacts subsequent behavior. Objective Identify regions of the brain activated and examine associations between activation and behavior. Methods This was a pilot study to assess physical activity, sedentary time, and glucose levels over 14 days in 33 adults (aged 30 to 60 years). Extracted accelerometry, inclinometry, and interstitial glucose data informed the construction of personalized feedback messages (eg, average number of steps per day). These messages were subsequently presented visually to participants during fMRI. Participant physical activity levels and sedentary time were assessed again for 8 days following exposure to this personalized feedback. Results Independent tests identified significant activations within the prefrontal cortex in response to glucose feedback compared with behavioral feedback (P<.001). Reductions in mean sedentary time (589.0 vs 560.0 minutes per day, P=.014) were observed. Activation in the subgyral area had a moderate correlation with minutes of moderate-to-vigorous physical activity (r=0.392, P=.043). Conclusion Presenting personalized glucose feedback resulted in significantly more brain activation when compared with behavior. Participants reduced time spent sedentary at follow-up. Research on deploying behavioral and physiological feedback warrants further investigation. PMID:29117928

Interruptin B induces brown adipocyte differentiation and glucose consumption in adipose-derived stem cells

PubMed Central

KAEWSUWAN, SIREEWAN; PLUBRUKARN, ANUCHIT; UTSINTONG, MALEERUK; KIM, SEOK-HO; JEONG, JIN-HYUN; CHO, JIN GU; PARK, SANG GYU; SUNG, JONG-HYUK

2016-01-01

Interruptin B has been isolated from Cyclosorus terminans, however, its pharamcological effect has not been fully identified. In the present study, the effects of interruptin B, from C. terminans, on brown adipocyte differentiation and glucose uptake in adipose-derived stem cells (ASCs) were investigated. The results revealed that interruptin B dose-dependently enhanced the adipogenic differentiation of ASCs, with an induction in the mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. In addition, interruptin B efficiently increased the number and the membrane potential of mitochondria and upregulated the mRNA expression levels of uncoupling protein (UCP)-1 and cyclooxygenase (COX)-2, which are all predominantly expressed in brown adipocytes. Interruptin B increased glucose consumption in differentiated ASCs, accompanied by the upregulation in the mRNA expression levels of glucose transporter (GLUT)-1 and GLUT-4. The computational analysis of molecular docking, a luciferase reporter assay and surface plasmon resonance confirmed the marked binding affinity of interruptin B to PPAR-α and PPAR-γ (KD values of 5.32 and 0.10 µM, respectively). To the best of our knowledge, the present study is the first report to show the stimulatory effects of interruptin B on brown adipocyte differentiation and glucose uptake in ASCs, through its role as a dual PPAR-α and PPAR-γ ligand. Therefore, interruptin B could be further developed as a therapeutic agent for the treatment of diabetes. PMID:26781331

Clinical usefulness of the thickness of preperitoneal and subcutaneous fat layer in the abdomen estimated by ultrasonography for diagnosing abdominal obesity in each type of impaired glucose tolerance in man.

PubMed

Soyama, Akiko; Nishikawa, Tetsuo; Ishizuka, Toshiharu; Ito, Hiroko; Saito, Jun; Yagi, Kazuo; Saito, Yasushi

2005-04-01

For this study we enrolled 1,615 males who were admitted to our hospital for a general health check-up. Plasma glucose (PG) and insulin were measured during 75 g OGTT, and abdominal obesity was assessed by ultrasonography in all subjects. We divided them into several groups: normal glucose tolerance (NGT), high-normal glucose tolerance (h-NGT) who showed >10.0 nmol/l at 1 hr PG among those with NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and DM, according to the results of 75 g OGTT. The aim of the present study was to clarify the clinical characteristics of pre-diabetic disorders relating to metabolic syndrome by comparing various parameters including body mass index (BMI), blood levels of various lipids and abdominal wall fat index (AFI) calculated from the thickness of preperitoneal (Pmax) and subcutaneous (Smin) fat layer in the abdomen estimated by ultrasonography with insulin sensitivity determined by homeostatic model assessment (HOMA-IR) in each type of abnormal glucose regulation as classified by PG changes in 75 g OGTT. We also investigated the relationship between insulin secretion capability and insulin sensitivity to delineate the characteristics of each type of abnormal glucose regulation, and compared the area under the insulin curve (AUCins) and the time axis, and the ability of early insulin secretion by glucose loading (insulinogenic index: I.I.) in each type of abnormal glucose regulation. There was a significant positive correlation between HOMA-IR and Smin or Pmax, suggesting that Smin and Pmax may reflect insulin sensitivity. Abdominal obesity, which was diagnosed from the data of AFI, was present in the h-NGT and IFG + IGT groups, suggesting that those groups belong to the clinical entity of metabolic syndrome. HOMA-IR was higher in IFG than in IGT, although I.I. was reduced and AUCins was increased in IFG as well as in IGT. h-NGT demonstrated a slightly lower I.I. and higher AUCins, compared with IGT. IFG demonstrated much stronger insulin resistance than IGT, although I.I. was reduced and AUCins was increased in IFG and IGT. Thus, it is suggested that insulin sensitivity may partly account for the difference in pathogenesis between IFG and IGT; and that h-NGT, which showed abdominal obesity assessed as AFI by ultrasonography, should be recognized as a disease state of metabolic syndrome with impaired glucose regulation.

Variable classifications of glycemic index determined by glucose meters.

PubMed

Lin, Meng-Hsueh Amanda; Wu, Ming-Chang; Lin, Jenshinn

2010-07-01

THE STUDY EVALUATED AND COMPARED THE DIFFERENCES OF GLUCOSE RESPONSES, INCREMENTAL AREA UNDER CURVE (IAUC), GLYCEMIC INDEX (GI) AND THE CLASSIFICATION OF GI VALUES BETWEEN MEASURED BY BIOCHEMICAL ANALYZER (FUJI AUTOMATIC BIOCHEMISTRY ANALYZER (FAA)) AND THREE GLUCOSE METERS: Accue Chek Advantage (AGM), BREEZE 2 (BGM), and Optimum Xceed (OGM). Ten healthy subjects were recruited for the study. The results showed OGM yield highest postprandial glucose responses of 119.6 +/- 1.5, followed by FAA, 118.4 +/- 1.2, BGM, 117.4 +/- 1.4 and AGM, 112.6 +/- 1.3 mg/dl respectively. FAA reached highest mean IAUC of 4156 +/- 208 mg x min/dl, followed by OGM (3835 +/- 270 mg x min/dl), BGM (3730 +/- 241 mg x min/dl) and AGM (3394 +/- 253 mg x min/dl). Among four methods, OGM produced highest mean GI value than FAA (87 +/- 5) than FAA, followed by BGM and AGM (77 +/- 1, 68 +/- 4 and 63 +/- 5, p<0.05). The results suggested that the AGM, BGM and OGM are more variable methods to determine IAUC, GI and rank GI value of food than FAA. The present result does not necessarily apply to other glucose meters. The performance of glucose meter to determine GI value of food should be evaluated and calibrated before use.

Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose, lipid profiles and insulin sensitivity in high-fat diet-fed mice by modulating expression of genes in peroxisome proliferator-activated receptor signaling pathway.

PubMed

Zhou, Mei-Cen; Yu, Ping; Sun, Qi; Li, Yu-Xiu

2016-03-01

Uncoupling protein 2 (UCP2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver-associated signaling pathway by expression profiling analysis. Four-week-old male UCP2-/- mice and UCP2+/+ mice were randomly assigned to four groups: UCP2-/- on a high-fat diet, UCP2-/- on a normal chow diet, UCP2+/+ on a high-fat diet and UCP2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array. The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β-cell function were improved in the UCP2-/- group on high-fat diet. Enhanced insulin sensitivity was observed in the UCP2-/- group. The differentially expressed genes were mapped to 23 pathways (P < 0.05). We concentrated on the 'peroxisome proliferator-activated receptor (PPAR) signaling pathway' (P = 3.19 × 10(-11)), because it is closely associated with the regulation of glucose and lipid profiles. In the PPAR signaling pathway, seven genes (PPARγ, Dbi, Acsl3, Lpl, Me1, Scd1, Fads2) in the UCP2-/- mice were significantly upregulated. The present study used gene arrays to show that activity of the PPAR signaling pathway involved in the improvement of glucose and lipid metabolism in the liver of UCP2-deficient mice on a long-term high-fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The manipulation of UCP2 protein expression could represent a new strategy for the prevention and treatment of diabetes.

Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat.

PubMed

Sampath, Sathish; Karundevi, Balasubramanian

2014-10-01

Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150 mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1(Tyr632), p-Akt(Ser473), β-arrestin-2, c-Src, p-AS160(Thr642), and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.

Aqueous glucose measurement using differential absorption-based frequency domain optical coherence tomography at wavelengths of 1310 nm and 1625 nm

NASA Astrophysics Data System (ADS)

John, Pauline; Manoj, Murali; Sujatha, N.; Vasa, Nilesh J.; Rao, Suresh R.

2015-07-01

This work presents a combination of differential absorption technique and frequency domain optical coherence tomography for detection of glucose, which is an important analyte in medical diagnosis of diabetes. Differential absorption technique is used to detect glucose selectively in the presence of interfering species especially water and frequency domain optical coherence tomography (FDOCT) helps to obtain faster acquisition of depth information. Two broadband super-luminescent diode (SLED) sources with centre wavelengths 1586 nm (wavelength range of 1540 to 1640 nm) and 1312 nm (wavelength range of 1240 to 1380 nm) and a spectral width of ≍ 60 nm (FWHM) are used. Preliminary studies on absorption spectroscopy using various concentrations of aqueous glucose solution gave promising results to distinguish the absorption characteristics of glucose at two wavelengths 1310 nm (outside the absorption band of glucose) and 1625 nm (within the absorption band of glucose). In order to mimic the optical properties of biological skin tissue, 2% and 10% of 20% intralipid with various concentrations of glucose (0 to 4000 mg/dL) was prepared and used as sample. Using OCT technique, interference spectra were obtained using an optical spectrum analyzer with a resolution of 0.5 nm. Further processing of the interference spectra provided information on reflections from the surfaces of the cuvette containing the aqueous glucose sample. Due to the absorption of glucose in the wavelength range of 1540 nm to 1640 nm, a trend of reduction in the intensity of the back reflected light was observed with increase in the concentration of glucose.

Influence of insulin on glucose metabolism and energy expenditure in septic patients

PubMed Central

Rusavy, Zdenek; Sramek, Vladimir; Lacigova, Silvie; Novak, Ivan; Tesinsky, Pavel; Macdonald, Ian A

2004-01-01

Introduction It is recognized that administration of insulin with glucose decreases catabolic response in sepsis. The aim of the present study was to compare the effects of two levels of insulinaemia on glucose metabolism and energy expenditure in septic patients and volunteers. Methods Glucose uptake, oxidation and storage, and energy expenditure were measured, using indirect calorimetry, in 20 stable septic patients and 10 volunteers in a two-step hyperinsulinaemic (serum insulin levels 250 and 1250 mIU/l), euglycaemic (blood glucose concentration 5 mmol/l) clamp. Differences between steps of the clamp (from serum insulin 1250 to 250 mIU/l) for all parameters were calculated for each individual, and compared between septic patients and volunteers using the Wilcoxon nonpaired test. Results Differences in glucose uptake and storage were significantly less in septic patients. The differences in glucose oxidation between the groups were not statistically significant. Baseline energy expenditure was significantly higher in septic patients, and there was no significant increase in either step of the clamp in this group; when comparing the two groups, the differences between steps were significantly greater in volunteers. Conclusion A hyperdynamic state of sepsis leads to a decrease in glucose uptake and storage in comparison with healthy volunteers. An increase in insulinaemia leads to an increase in all parameters of glucose metabolism, but the increases in glucose uptake and storage are significantly lower in septic patients. A high level of insulinaemia in sepsis increases glucose uptake and oxidation significantly, but not energy expenditure, in comparison with volunteers. PMID:15312220

Optical monitoring of glucose demand and vascular delivery in a preclinical murine model

NASA Astrophysics Data System (ADS)

Frees, Amy; Rajaram, Narasimhan; McCachren, Sam; Vaz, Alex; Dewhirst, Mark; Ramanujam, Nimmi

2014-03-01

Targeted therapies such as PI3K inhibition can affect tumor vasculature, and hence delivery of imaging agents like FDG, while independently modifying intrinsic glucose demand. Therefore, it is important to identify whether perceived changes in glucose uptake are caused by vascular or true metabolic changes. This study sought to develop an optical strategy for quantifying tissue glucose uptake free of cross-talk from tracer delivery effects. Glucose uptake kinetics were measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-Dglucose (2-NBDG), and 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-L-glucose (2-NBDLG) was used as a control to report on non-specific uptake. Vascular oxygenation (SO2) was calculated from wavelength-dependent hemoglobin absorption. We have previously shown that the rate of 2-NBDG delivery in vivo profoundly affects perceived demand. In this study, we investigated the potential of the ratio of 2-NBDG uptake to the rate of delivery (2-NBDG60/RD) to report on 2-NBDG demand in vivo free from confounding delivery effects. In normal murine tissue, we show that 2-NBDG60/RD can distinguish specific uptake from non-specific cell membrane binding, whereas fluorescence intensity alone cannot. The ratio 2-NBDG60/RD also correlates with blood glucose more strongly than 2-NBDG60 does in normal murine tissue. Additionally, 2-NBDG60/RD can distinguish normal murine tissue from a murine metastatic tumor across a range of SO2 values. The results presented here indicate that the ratio of 2-NBDG uptake to the rate of 2-NBDG delivery (2- NBDG60/RD) is superior to 2-NBDG intensity alone for quantifying changes in glucose demand.

Metabolic and hemodynamic effects of sodium-dependent glucose cotransporter 2 inhibitors on cardio-renal protection in the treatment of patients with type 2 diabetes mellitus.

PubMed

Kashiwagi, Atsunori; Maegawa, Hiroshi

2017-07-01

The specific sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease because of urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole-body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors. In addition, SGLT2 inhibitors have profound hemodynamic effects including diuresis, dehydration, weight loss and lowering blood pressure. The most recent findings on SGLT2 inhibitors come from results of the Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial. SGLT2 inhibitors exert extremely unique and cardio-renal protection through metabolic and hemodynamic effects, with long-term durability on the reduction of blood glucose, bodyweight and blood pressure. Although a site of action of SGLT2 inhibitors is highly specific to inhibit renal glucose reabsorption, whole-body energy metabolism, and hemodynamic and renal functions are profoundly modulated during the treatment of SGLT2 inhibitors. Previous studies suggest multifactorial clinical benefits and safety concerns of SGLT2 inhibitors. Although ambivalent clinical results of this drug are still under active discussion, the present review summarizes promising recent evidence on the cardio-renal and metabolic benefits of SGLT2 inhibitors in the treatment of type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Citral, A Monoterpene Protect Against High Glucose Induced Oxidative Injury in HepG2 Cell In Vitro-An Experimental Study.

PubMed

Subramaniyan, Sri Devi; Natarajan, Ashok Kumar

2017-08-01

Diabetes mellitus, a major metabolic disorder associated with hyperglycaemia is one of the leading cause of death in many developed countries. However, use of natural phytochemicals have been proved to have a protective effect against oxidative damage. To investigate the effect of citral, a monoterpene on high glucose induced cytotoxicity and oxidative stress in human hepatocellular liver carcinoma (Hep G2) cell line. Cells were treated with 50 mM concentration of glucose for 24 hours incubation following citral (30 μM) was added to confluent HepG2 cells. Cell viability, Reactive Oxygen Species (ROS) generation, DNA damage, lipid peroxidation, antioxidants and Mitogen Activated Protein Kinases (MAPKs) signaling were assessed in citral and/or high glucose induced HepG2 cells. Cells treated with glucose (50 mM), resulted in increased cytotoxicity, ROS generation, DNA damage, lipid peroxidation and depletion of enzymatic and non enzymatic antioxidants. In contrast, treatment with citral (30 μM) significantly decreased cell cytotoxicity, ROS generation, DNA damage, lipid peroxidation and increased antioxidants enzymes in high glucose induced HepG2 cells. In addition, the present study highlighted that high glucose treated cells showed increased expression of Extracellular Signal Regulated Protein Kinase-1 (ERK-1), c-Jun N-terminal Kinase (JNK) and p38 in HepG2 cells. On the other hand treatment with citral significantly suppressed the expression of ERK-1, JNK and p38 in high glucose induced HepG2 cells. Citral protects against high glucose induced oxidative stress through inhibiting ROS activated MAPK signaling pathway in HepG2 cells.

Association of late-night carbohydrate intake with glucose tolerance among pregnant African American women.

PubMed

Chandler-Laney, Paula C; Schneider, Camille R; Gower, Barbara A; Granger, Wesley M; Mancuso, Melissa S; Biggio, Joseph R

2016-10-01

Obesity and late-night food consumption are associated with impaired glucose tolerance. Late-night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night-time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non-diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m(-2) ; Ob, ≥30 kg m(-2) ). Third trimester free-living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75-g oral glucose tolerance test. Women in the Ob group reported greater average 24-h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late-night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night-time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late-night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy. © 2015 John Wiley & Sons Ltd.

Mitochondrial dysfunction precedes depression of AMPK/AKT signaling in insulin resistance induced by high glucose in primary cortical neurons.

PubMed

Peng, Yunhua; Liu, Jing; Shi, Le; Tang, Ying; Gao, Dan; Long, Jiangang; Liu, Jiankang

2016-06-01

Recent studies have demonstrated brain insulin signaling impairment and mitochondrial dysfunction in diabetes. Hyperinsulinemia and hyperlipidemia arising from diabetes have been linked to neuronal insulin resistance, and hyperglycemia induces peripheral sensory neuronal impairment and mitochondrial dysfunction. However, how brain glucose at diabetic conditions elicits cortical neuronal insulin signaling impairment and mitochondrial dysfunction remains unknown. In the present study, we cultured primary cortical neurons with high glucose levels and investigated the neuronal mitochondrial function and insulin response. We found that mitochondrial function was declined in presence of 10 mmol/L glucose, prior to the depression of AKT signaling in primary cortical neurons. We further demonstrated that the cerebral cortex of db/db mice exhibited both insulin resistance and loss of mitochondrial complex components. Moreover, we found that adenosine monophosphate-activated protein kinase (AMPK) inactivation is involved in high glucose-induced mitochondrial dysfunction and insulin resistance in primary cortical neurons and neuroblastoma cells, as well as in cerebral cortex of db/db mice, and all these impairments can be rescued by mitochondrial activator, resveratrol. Taken together, our results extend the finding that high glucose (≥10 mmol/L) comparable to diabetic brain extracellular glucose level leads to neuronal mitochondrial dysfunction and resultant insulin resistance, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. We found that high glucose (≥10 mmol/L), comparable to diabetic brain extracellular glucose level, leads to neuronal mitochondrial dysfunction and resultant insulin resistance in an AMPK-dependent manner, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. © 2016 International Society for Neurochemistry.

Effects of intravenous glucose on dopaminergic function in the human brain in vivo.

PubMed

Haltia, Lauri T; Rinne, Juha O; Merisaari, Harri; Maguire, Ralph P; Savontaus, Eriika; Helin, Semi; Någren, Kjell; Kaasinen, Valtteri

2007-09-01

Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that glucose would induce dopamine release and positive ratings (e.g., satiety) in Behavioral Analog Scales, particularly in food-deprived lean subjects. [(11)C]raclopride PET was performed for 12 lean (mean BMI = 22 kg/m(2)) and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects. Each subject was imaged twice in a blinded counter-balanced setting, after 300 mg/kg i.v. glucose and after i.v. placebo. Dopamine D2 receptor binding potentials (BPs) were estimated. The voxel-based analysis of the baseline scans indicated lower striatal BPs in the overweight group and a negative correlation between BMIs and BPs. Intravenous glucose did not have a significant effect on BPs in overweight or lean subjects (male and female groups combined). However, BP changes were opposite in the two gender groups. In male subjects, significant BP reductions after glucose were seen in the right and left caudate nucleus, left putamen, and right thalamus. In female subjects, increases in BP secondary to glucose were seen in the right caudate nucleus and right and left putamen. The sexually dimorphic effect of glucose was seen in both overweight and lean subjects. Although gender differences were not among the a priori hypotheses of the present study and, therefore, they must be considered to be preliminary findings, we postulate that this observation is a reflection of an interaction between glucose, sex steroids (estrogen), leptin, and dopamine.

Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study ("Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo").

PubMed

Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle-Pascual, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

2011-05-01

Hyperglycaemia has been associated with increased platelet reactivity and impaired prognosis in patients with acute coronary syndrome (ACS). Whether platelet reactivity can be reduced by lowering glucose in this setting is unknown. The aim of this study was to assess the functional impact of intensive glucose control with insulin on platelet reactivity in patients admitted with ACS and hyperglycaemia. This is a prospective, randomised trial evaluating the effects of either intensive glucose control (target glucose 80-120 mg/dl) or conventional control (target glucose 180 mg/dl or less) with insulin on platelet reactivity in patients with ACS and hyperglycaemia. The primary endpoint was platelet aggregation following stimuli with 20 μM ADP at 24 h and at hospital discharge. Aggregation following collagen, epinephrine and thrombin receptor-activated peptide, as well as P2Y₁₂ reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin were also measured. Of the 115 patients who underwent random assignment, 59 were assigned to intensive and 56 to conventional glucose control. Baseline platelet functions and inhospital management were similar in both groups. Maximal aggregation after ADP stimulation at hospital discharge was lower in the intensive group (47.9 ± 13.2% vs 59.1 ± 17.3%; p=0.002), whereas no differences were found at 24 h. Similarly all other parameters of platelet reactivity measured at hospital discharge were significantly reduced in the intensive glucose control group. In this randomised trial, early intensive glucose control with insulin in patients with ACS presenting with hyperglycaemia was found to decrease platelet reactivity. Clinical Trial Registration Number http://www.controlledtrials.com/ISRCTN35708451/ISRCTN35708451.

Placebo expectancy effects in the relationship between glucose and cognition.

PubMed

Green, M W; Taylor, M A; Elliman, N A; Rhodes, O

2001-08-01

The present study investigated the extent of expectancy in the ability of glucose to affect cognitive performance. Using a within-subjects design, subjects (n 26) completed four experimental sessions (in counterbalanced order and after an initial practice session) during which they were given a 500 ml drink 30 min prior to completing a cognitive assessment battery. In addition, all subjects completed a baseline practice session during which they were given no drink. During two of the sessions, subjects were given a drink containing 50 g glucose and on the other two they were given a drink containing aspartame. A balanced placebo design was used, such that for half the sessions subjects were accurately informed as to the content of the drink (glucose or aspartame), whereas in the other two sessions they were misinformed as to the content of the drink. The task battery comprised a 6 min visual analogue of the Bakan vigilance task, an immediate verbal free-recall task, an immediate verbal recognition memory task and a measure of motor speed (two-finger tapping). Blood glucose and self-reported mood were also recorded at several time points during each session. Glucose administration was found to improve recognition memory times, in direct contrast to previous findings in the literature. Glucose administration also improved performance on the Bakan task (relative to the control drink), but only in sessions where subjects were informed that they would receive glucose and not when they were told that they would receive aspartame. There were no effects either of the nature of the drink or expectancy on the other measures. These results are interpreted in terms of there being some contribution of expectancy concerning the positive effects of glucose on cognition in studies which have not used an equi-sweet dose of aspartame as a control drink.

Monoterpenes: Novel insights into their biological effects and roles on glucose uptake and lipid metabolism in 3T3-L1 adipocytes.

PubMed

Tan, X C; Chua, K H; Ravishankar Ram, M; Kuppusamy, U R

2016-04-01

Various strategies have been adopted to combat complications caused by Type 2 diabetes mellitus and controlled diet is one of them. Monoterpenes, major constituents of essential oils, are synthesized and widely used as artificial food flavors. A series of twelve monoterpenes were assessed in the present study. Monoterpenes, exhibited low 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity even at high concentrations. Some monoterpenes inhibited α-amylase and α-glucosidase activity and stimulated glucose uptake and lipolysis. Monoterpenes such as (R)-(+)-limonene stimulated both glucose uptake (17.4%) and lipolysis (17.7%); the mRNA expression of glucose transporter 1 (GLUT1) was upregulated but glucose transporter 4 (GLUT4) was unaffected, and adipose triglyceride lipase (ATGL) was suppressed. Taken together, the selected monoterpenes may not confer strong protection against free radicals but nevertheless, their positive influence on lipid and glucose metabolism may have potential in the control of obesity and Type 2 diabetes mellitus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Decrease of Plasma Glucose by Hibiscus taiwanensis in Type-1-Like Diabetic Rats

PubMed Central

Wang, Lin-Yu; Chung, Hsien-Hui

2013-01-01

Hibiscus taiwanensis (Malvaceae) is widely used as an alternative herb to treat disorders in Taiwan. In the present study, it is used to screen the effect on diabetic hyperglycemia in streptozotocin-induced diabetic rats (STZ-diabetic rats). The extract of Hibiscus taiwanensis showed a significant plasma glucose-lowering action in STZ-diabetic rats. Stems of Hibiscus taiwanensis are more effective than other parts to decrease the plasma glucose in a dose-dependent manner. Oral administration of Hibiscus taiwanensis three times daily for 3 days into STZ-diabetic rats increased the sensitivity to exogenous insulin showing an increase in insulin sensitivity. Moreover, similar repeated administration of Hibiscus taiwanensis for 3 days in STZ-diabetic rats produced a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Taken together, our results suggest that Hibiscus taiwanensis has the ability to lower plasma glucose through an increase in glucose utilization via elevation of skeletal GLUT 4 and decrease of hepatic PEPCK in STZ-diabetic rats. PMID:23690841

A NMR study of parasitized Tenebrio molitor and Hymenolepis diminuta cysticercoids.

PubMed

Schoen, J; Modha, A; Maslow, K; Novak, M; Blackburn, B J

1996-07-01

In vivo NMR spectra of uninfected and Hymenolepis diminuta-infected Tenebrio molitor fed D-(1-13C)glucose showed that infected beetles of both sexes had a significantly higher ratio for (glycogen C1/lipid (CH2)n) than the corresponding controls. Quantitative metabolic profiles and the per cent 13C-label in metabolites, based on NMR of perchloric acid extracts, are presented for control and infected beetles fed D-(1-13C)glucose and for H. diminuta cysticercoids. Female beetles, both control and infected, contained more glycogen than their male counterparts and infected beetles of both sexes possessed less glycerophos-phocholine, but more glycogen and a higher percentage label in glucose and trehalose than their respective controls. Label was also incorporated into glycogen, succinate, acetate, alanine and lactate. Extracts of cysticercoids from beetles fed D-(1-13C)glucose contained the following labelled compounds, in order of decreasing per cent 13C label: glucose, trehalose, alanine, succinate, lactate, glycogen and acetate. In vitro cultivation experiments, employing D-(1-13C)glucose, revealed that trehalose found in cysticercoids was of parasite, and not beetle, origin.

Rapid quantitative detection of glucose content in glucose injection by reaction headspace gas chromatography.

PubMed

Xie, Wei-Qi; Gong, Yi-Xian; Yu, Kong-Xian

2017-10-20

This work investigates an automated technique for rapid detecting the glucose content in glucose injection by reaction headspace gas chromatography (HS-GC). This method is based on the oxidation reaction of glucose in glucose injection with potassium dichromate. The carbon dioxide (CO 2 ) formed from the oxidation reaction can be quantitatively detected by GC. The results show that the relative standard deviation (RSD) of the present method was within 2.91%, and the measured glucose contents in glucose injection closely match those quantified by the reference method (relative differences <6.45%). The new HS-GC technique is rapid, practical and can be used to the batch detection of the glucose content in glucose injection related applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of protein phase diagrams by microbatch experiments: exploring the influence of precipitants and pH.

PubMed

Baumgartner, Kai; Galm, Lara; Nötzold, Juliane; Sigloch, Heike; Morgenstern, Josefine; Schleining, Kristina; Suhm, Susanna; Oelmeier, Stefan A; Hubbuch, Jürgen

2015-02-01

Knowledge of protein phase behavior is essential for downstream process design in the biopharmaceutical industry. Proteins can either be soluble, crystalline or precipitated. Additionally liquid-liquid phase separation, gelation and skin formation can occur. A method to generate phase diagrams in high throughput on an automated liquid handling station in microbatch scale was developed. For lysozyme from chicken egg white, human lysozyme, glucose oxidase and glucose isomerase phase diagrams were generated at four different pH values – pH 3, 5, 7 and 9. Sodium chloride, ammonium sulfate, polyethylene glycol 300 and polyethylene glycol 1000 were used as precipitants. Crystallizing conditions could be found for lysozyme from chicken egg white using sodium chloride, for human lysozyme using sodium chloride or ammonium sulfate and glucose isomerase using ammonium sulfate. PEG caused destabilization of human lysozyme and glucose oxidase solutions or a balance of stabilizing and destabilizing effects for glucose isomerase near the isoelectric point. This work presents a systematic generation and extensive study of phase diagrams of proteins. Thus, it adds to the general understanding of protein behavior in liquid formulation and presents a convenient methodology applicable to any protein solution. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparative influence of propranolol and verapamil on glycemic control and histamine sensitivity associated with L-thyroxine-induced hyperthyroidism - an experimental study.

PubMed

Bhatt, Parloop A; Makwana, Dharmesh

2008-02-01

The present investigation was undertaken to study the comparative effectiveness of beta-adrenergic antagonist propranolol and calcium channel blocker verapamil on L-thyroxine-induced alteration on glycemic control and histamine sensitivity on rats and guinea pigs, respectively. Injection of L-thyroxine sodium every alternate day for 3 weeks in guinea pigs (75 microg/kg, i.p.) and rats (75 mg/kg, s.c.) produced a condition similar to thyrotoxicosis. Verapamil and propranolol administered daily in the third week along with L-thyroxine to two separate groups of hyperthyroid animals reversed thyroxine-induced loss in body weight, reduction in serum TSH levels, and rise in body temperature. Effect on glucose metabolism and insulin sensitivity was studied on rats. Compared to normal rats, L-thyroxine-treated animals showed a state of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. Propranolol (10 mg/kg, i.p.) treatment significantly decreased fasting serum glucose levels without affecting serum insulin levels, AUC glucose, and K(ITT) values. Treatment with verapamil (5 mg/kg, i.p.) significantly reduced fasting serum glucose and insulin levels, AUC glucose, and significantly increased K(ITT) values. Effect of propranolol (15 mg/kg, orally) and verapamil (20 mg/kg, orally) treatment on histamine sensitivity was studied on L-thyroxine-treated guinea pigs. Compared to normal guinea pigs, L-thyroxine-treated guinea pigs showed an increased sensitivity to histamine-induced asphyxia. Verapamil treatment reversed this increased histamine sensitivity while propranolol aggravated it. In conclusion, compared to propranolol, verapamil has advantageous effects on glucose metabolism, insulin and histamine sensitivity and could therefore be a valuable addition as an adjunctive therapy option currently available for thyrotoxicosis associated with diabetes and/or anaphylaxis.

Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.

PubMed

Vickers, Steven P; Cheetham, Sharon C; Headland, Katie R; Dickinson, Keith; Grempler, Rolf; Mayoux, Eric; Mark, Michael; Klein, Thomas

2014-01-01

The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.

Nutritional implications of olives and sugar: attenuation of post-prandial glucose spikes in healthy volunteers by inhibition of sucrose hydrolysis and glucose transport by oleuropein.

PubMed

Kerimi, Asimina; Nyambe-Silavwe, Hilda; Pyner, Alison; Oladele, Ebun; Gauer, Julia S; Stevens, Yala; Williamson, Gary

2018-03-09

The secoiridoid oleuropein, as found in olives and olive leaves, modulates some biomarkers of diabetes risk in vivo. A possible mechanism may be to attenuate sugar digestion and absorption. We explored the potential of oleuropein, prepared from olive leaves in a water soluble form (OLE), to inhibit digestive enzymes (α-amylase, maltase, sucrase), and lower [ 14 C(U)]-glucose uptake in Xenopus oocytes expressing human GLUT2 and [ 14 C(U)]-glucose transport across differentiated Caco-2 cell monolayers. We conducted 7 separate crossover, controlled, randomised intervention studies on healthy volunteers (double-blinded and placebo-controlled for the OLE supplement) to assess the effect of OLE on post-prandial blood glucose after consumption of bread, glucose or sucrose. OLE inhibited intestinal maltase, human sucrase, glucose transport across Caco-2 monolayers, and uptake of glucose by GLUT2 in Xenopus oocytes, but was a weak inhibitor of human α-amylase. OLE, in capsules, in solution or as naturally present in olives, did not affect post-prandial glucose derived from bread, while OLE in solution attenuated post-prandial blood glucose after consumption of 25 g sucrose, but had no effect when consumed with 50 g of sucrose or glucose. The combined inhibition of sucrase activity and of glucose transport observed in vitro was sufficient to modify digestion of low doses of sucrose in healthy volunteers. In comparison, the weak inhibition of α-amylase by OLE was not enough to modify blood sugar when consumed with a starch-rich food, suggesting that a threshold potency is required for inhibition of digestive enzymes in order to translate into in vivo effects.

Single-Walled Carbon Nanotube-Based Near-Infrared Optical Glucose Sensors toward In Vivo Continuous Glucose Monitoring

PubMed Central

Yum, Kyungsuk; McNicholas, Thomas P.; Mu, Bin; Strano, Michael S.

2013-01-01

This article reviews research efforts on developing single-walled carbon nanotube (SWNT)-based near-infrared (NIR) optical glucose sensors toward long-term in vivo continuous glucose monitoring (CGM). We first discuss the unique optical properties of SWNTs and compare SWNTs with traditional organic and nanoparticle fluorophores regarding in vivo glucose-sensing applications. We then present our development of SWNT-based glucose sensors that use glucose-binding proteins and boronic acids as a high-affinity molecular receptor for glucose and transduce binding events on the receptors to modulate SWNT fluorescence. Finally, we discuss opportunities and challenges in translating the emerging technology of SWNT-based NIR optical glucose sensors into in vivo CGM for practical clinical use. PMID:23439162

Neuroprotective effects of ginsenoside Rb1 on high glucose-induced neurotoxicity in primary cultured rat hippocampal neurons.

PubMed

Liu, Di; Zhang, Hong; Gu, Wenjuan; Liu, Yuqin; Zhang, Mengren

2013-01-01

Ginsenoside Rb1 is one of the main active principles in traditional herb ginseng and has been reported to have a wide variety of neuroprotective effects. Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, so the present study aimed to observe the effects of ginsenoside Rb1 on ER stress signaling pathways in high glucose-treated hippocampal neurons. The results from MTT, TUNEL labeling and Annexin V-FITC/PI/Hoechst assays showed that incubating neurons with 50 mM high glucose for 72 h decreased cell viability and increased the number of apoptotic cells whereas treating neurons with 1 μM Rb1 for 72 h protected the neurons against high glucose-induced cell damage. Further molecular mechanism study demonstrated that Rb1 suppressed the activation of ER stress-associated proteins including protein kinase RNA (PKR)-like ER kinase (PERK) and C/EBP homology protein (CHOP) and downregulation of Bcl-2 induced by high glucose. Moreover, Rb1 inhibited both the elevation of intracellular reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential induced by high glucose. In addition, the high glucose-induced cell apoptosis, activation of ER stress, ROS accumulation and mitochondrial dysfunction can also be attenuated by the inhibitor of ER stress 4-phenylbutyric acid (4-PBA) and anti-oxidant N-acetylcysteine(NAC). In conclusion, these results suggest that Rb1 may protect neurons against high glucose-induced cell injury through inhibiting CHOP signaling pathway as well as oxidative stress and mitochondrial dysfunction.

Effects of glucose, insulin and triiodothyroxine on leptin and leptin receptor expression and the effects of leptin on activities of enzymes related to glucose metabolism in grass carp (Ctenopharyngodon idella) hepatocytes.

PubMed

Lu, Rong-Hua; Zhou, Yi; Yuan, Xiao-Chen; Liang, Xu-Fang; Fang, Liu; Bai, Xiao-Li; Wang, Min; Zhao, Yu-Hua

2015-08-01

Leptin is an important regulator of appetite and energy expenditure in mammals, but its role in fish metabolism control is poorly understood. Our previous studies demonstrated that leptin has an effect on the regulation of food intake and energy expenditure as well as lipid metabolism (stimulation of lipolysis and inhibition of adipogenesis) in the grass carp Ctenopharyngodon idella. To further investigate the role of leptin in fish, the effects of glucose, insulin and triiodothyroxine (T3) on the expression levels of leptin and leptin receptor (Lepr) and the effects of leptin on the activities of critical glucose metabolism enzymes in grass carp hepatocytes were evaluated in the present study. Our data indicated that leptin gene expression was induced by glucose in a dose-dependent manner, while Lepr gene expression exhibited a biphasic change. A high dose of insulin (100 ng/mL) significantly up-regulated the expression of leptin and Lepr. Leptin expression was markedly up-regulated by a low concentration of T3 but inhibited by a high concentration of T3. T3 up-regulated Lepr expression in a dose-dependent manner. Together, these data suggest that leptin had a close relationship with three factors (glucose, insulin and T3) and might participate in the regulation of glucose metabolism in grass carp. In addition, we also found that leptin affected the activities of key enzymes that are involved in glucose metabolism, which might be mediated by insulin receptor substrate-phosphoinositol 3-kinase signaling.

Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates insulin resistance by upregulating glucose transporter-4, peroxisome proliferator-activated receptor-gamma, adiponectin, and leptin levels in vitro

PubMed Central

Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V.; Manjunath, Kirangadur; Viswanatha, Gollapalle L.; Ashok, Godavarthi

2016-01-01

Aims: The present study was undertaken to evaluate the effect of methanolic leaf extract of Gymnema sylvestre (MLGS) on glucose transport (GLUT) and insulin resistance in vitro. Materials and Methods: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) and GLUT-4 expression were assessed in L6 myotubes for concluding the GLUT activity, and adiponectin and leptin expression was studied in 3T3 L1 murine adipocyte cell line to determine the effect of MLGS (250-750 μg/ml) on insulin resistance. Results: The findings of the experiments have demonstrated a significant and dose-dependent increase in glucose uptake in all the tested concentrations of MLGS, further the glucose uptake activity of MLGS (750 μg/ml) was at par with rosiglitazone (50 μg/ml). Concomitantly, MLGS has shown enhanced GLUT-4 and PPAR-γ gene expressions in L6 myotubes. Furthermore, cycloheximide (CHX) had completely abolished the glucose uptake activity of MLGS when co-incubated, which further confirmed that glucose uptake activity of MLGS was linked to enhanced expression of GLUT-4 and PPAR-γ. In addition, in another experimental set, MLGS showed enhanced expression of adiponectin and leptin, thus confirms the ameliorative effect of MLGS on insulin resistance. Conclusion: These findings suggest that MLGS has an enhanced glucose uptake activity in L6 myotubes, and ameliorate the insulin resistance in 3T3 L1 murine adipocyte cell line in vitro. PMID:27104035

Anti-prediabetic effect of rose hip (Rosa canina) extract in spontaneously diabetic Torii rats.

PubMed

Chen, Si Jing; Aikawa, Chiwa; Yoshida, Risa; Kawaguchi, Tomoaki; Matsui, Toshiro

2017-09-01

Prediabetes, a high-risk state for developing diabetes showing impaired glucose tolerance but a normal fasting blood glucose level, has an increasing prevalence worldwide. However, no study investigating the prevention of impaired glucose tolerance at the prediabetic stage by anti-diabetic functional foods has been reported. Thus, the present study aimed to evaluate the anti-prediabetic effect of rose hip in a prediabetic rat model. Spontaneously diabetic Torii (SDT) rats were supplemented with hot-water extract of rose hip at a dose of 100 mg kg -1 body weight day -1 for 12 weeks. The results obtained showed that the supplementation of rose hip extract improved impaired glucose tolerance, promoted insulin secretion, preserved pancreatic beta-cell function and suppressed plasma advanced glycation end-products formation of methylglyoxal-derived hydroimidazolone (MG-H1) residue and N ϵ -carboxymethyl-lysine residues (e.g. MG-H1, control: 465.5 ± 43.8 versus rose hip: 59.1 ± 13.0 pmol mg protein -1 , P < 0.05) in SDT rats at the prediabetic stage (12-20 weeks old). The present study provides the first evidence showing that a hot-water extract of rose hip could exert an anti-prediabetic effect in a rat model. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes.

PubMed

Pentassuglia, Laura; Heim, Philippe; Lebboukh, Sonia; Morandi, Christian; Xu, Lifen; Brink, Marijke

2016-05-01

Nrg1β is critically involved in cardiac development and also maintains function of the adult heart. Studies conducted in animal models showed that it improves cardiac performance under a range of pathological conditions, which led to its introduction in clinical trials to treat heart failure. Recent work also implicated Nrg1β in the regenerative potential of neonatal and adult hearts. The molecular mechanisms whereby Nrg1β acts in cardiac cells are still poorly understood. In the present study, we analyzed the effects of Nrg1β on glucose uptake in neonatal rat ventricular myocytes and investigated to what extent mTOR/Akt signaling pathways are implicated. We show that Nrg1β enhances glucose uptake in cardiomyocytes as efficiently as IGF-I and insulin. Nrg1β causes phosphorylation of ErbB2 and ErbB4 and rapidly induces the phosphorylation of FAK (Tyr(861)), Akt (Thr(308) and Ser(473)), and its effector AS160 (Thr(642)). Knockdown of ErbB2 or ErbB4 reduces Akt phosphorylation and blocks the glucose uptake. The Akt inhibitor VIII and the PI3K inhibitors LY-294002 and Byl-719 abolish Nrg1β-induced phosphorylation and glucose uptake. Finally, specific mTORC2 inactivation after knockdown of rictor blocks the Nrg1β-induced increases in Akt-p-Ser(473) but does not modify AS160-p-Thr(642) or the glucose uptake responses to Nrg1β. In conclusion, our study demonstrates that Nrg1β enhances glucose uptake in cardiomyocytes via ErbB2/ErbB4 heterodimers, PI3Kα, and Akt. Furthermore, although Nrg1β activates mTORC2, the resulting Akt-Ser(473) phosphorylation is not essential for glucose uptake induction. These new insights into pathways whereby Nrg1β regulates glucose uptake in cardiomyocytes may contribute to the understanding of its regenerative capacity and protective function in heart failure. Copyright © 2016 the American Physiological Society.

Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis.

PubMed

Prévost, Gaëtan; Jeandel, Lydie; Arabo, Arnaud; Coëffier, Moïse; El Ouahli, Mariama; Picot, Marie; Alexandre, David; Gobet, Françoise; Leprince, Jérôme; Berrahmoune, Hind; Déchelotte, Pierre; Malagon, Maria; Bonner, Caroline; Kerr-Conte, Julie; Chigr, Fatiha; Lefebvre, Hervé; Anouar, Youssef; Chartrel, Nicolas

2015-08-01

26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a high-fat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic β-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Electrochemical characterization of the pyranose 2-oxidase variant N593C shows a complete loss of the oxidase function with full preservation of substrate (dehydrogenase) activity† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6cp06009a Click here for additional data file.

PubMed Central

Brugger, Dagmar; Sützl, Leander; Zahma, Kawah; Haltrich, Dietmar; Peterbauer, Clemens K.

2016-01-01

This study presents the first electrochemical characterization of the pyranose oxidase (POx) variant N593C (herein called POx-C), which is considered a promising candidate for future glucose-sensing applications. The resulting cyclic voltammograms obtained in the presence of various concentrations of glucose and mediator (1,4-benzoquinone, BQ), as well as the control experiments by addition of catalase, support the conclusion of a complete suppression of the oxidase function and oxygen reactivity at POx-C. Additionally, these electrochemical experiments demonstrate, contrary to previous biochemical studies, that POx-C has a fully retained enzymatic activity towards glucose. POx-C was immobilized on a special screen-printed electrode (SPE) based on carbon ink and grafted with gold-nanoparticles (GNP). Suppression of the oxygen reactivity at N593C-POx variant is a prerequisite for utilizing POx in electrochemical applications for glucose sensing. To our knowledge, this is the first report presented in the literature showing an absolute conversion of an oxidase into a fully active equivalent dehydrogenase via a single residue exchange. PMID:27808302

Effects of different levels of coconut fiber on blood glucose, serum insulin and minerals in rats.

PubMed

Sindurani, J A; Rajamohan, T

2000-01-01

The effect of neutral detergent fiber (NDF) from coconut kernel (Cocos nucifera L) in rats fed 5%, 15% and 30% level on the concentration of blood glucose, serum insulin and excretion of minerals was studied. Increase in the intake of fiber resulted in significant decrease in the level of blood glucose and serum insulin. Faecal excretion of Cu, Cr, Mn, Mg, Zn and Ca was found to increase in rats fed different levels of coconut fiber when compared to fiber free group. The result of the present investigation suggest that inclusion of coconut fiber in the diet results in significant hypoglycemic action.

Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling Pathway.

PubMed

Wang, Caijuan; Deng, Yujiao; Yue, Yenan; Chen, Wenting; Zhang, Yu; Shi, Guifang; Wu, Zhongming

2018-03-01

BACKGROUND Diabetes mellitus (DM) is characterized by a decreased blood level of glutamine (Gln), which may contribute to the disturbance in the effect of insulin on skeletal muscle. Therefore, it is crucial to study how to improve the effect of insulin on skeletal muscle by increasing Gln. In the present study, we investigated the effect of Gln on the hypoglycemic action of insulin in skeletal muscle L6 cells at high glucose levels through the insulin signaling pathway and glycogen synthesis pathway. MATERIAL AND METHODS The L6 cells were cultured in and stimulated by Gln and insulin. The glutamine analogue, L-Gamma-Glutamyl-p-nitroanilide (GPNA), was used for verifying the effect of Gln. The expression of insulin signaling molecules, including phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B (AKT), protein kinase C zeta (PKCz), and glucose transporter 4 (GLUT4), were detected by real-time PCR and Western blot analysis, GLUT4 translocation was observed by immunofluorescence staining, glycogen synthase kinase (GSK) was analyzed by Western blotting, and glucose uptake was measured by glucose oxidase method (GOD). RESULTS The results demonstrated that Gln combined with insulin remarkably up-regulated PI3K and PDK1 and also increased AKT and PKCz phosphorylation. The present study shows that Gln enhanced the impact of insulin on GLUT4 and its translocation. The results of glucose uptake and GSK phosphorylation further confirmed the hypoglycemic effect of Gln accompanied with insulin. The hypoglycemic effect of Gln was reversed by GPNA. CONCLUSIONS These findings suggest that Gln enhances the hypoglycemic role of insulin through the PI3K/AKT/GLUT4 signaling pathway and glycogen synthesis pathway.

Polarimetric glucose sensing using Brewster reflection applying a rotating retarder analyzer

NASA Astrophysics Data System (ADS)

Boeckle, Stefan; Rovati, Luigi L.; Ansari, Rafat R.

2003-10-01

Previously, we proposed a polarimetric method, that exploits the Brewster-reflection with the final goal of application to the human eye (reflection off the eye lens) for non-invasive glucose sensing. The linearly polarized reflected light of this optical scheme is rotated by the glucose molecules present in the aqueous humor, thus carries the blood glucose concentration information. A proof-of-concept experimental bench-top setup is presented, applying a multi-wavelength true phase measurement approach and a rotating phase retarder as an analyzer to measure the very small rotation angles and the complete polarization state of the measurement light.

The flavonoid-rich fraction of Coreopsis tinctoria promotes glucose tolerance regain through pancreatic function recovery in streptozotocin-induced glucose-intolerant rats.

PubMed

Dias, Teresa; Bronze, Maria Rosário; Houghton, Peter J; Mota-Filipe, Hélder; Paulo, Alexandra

2010-11-11

Infusions of Coreopsis tinctoria Nutt. flowering tops have been used traditionally in Portugal to control hyperglycaemia and a previous study revealed that daily administration of the infusion during a 3-week period promoted the recovery of glucose tolerance by a mechanism different from inhibition of glucose absorption and direct promotion of insulin secretion. We know report the study of the ethyl acetate fraction of Coreopsis tinctoria flowers infusion aiming to confirm flavonoids as bioactive metabolites. To give one step forward into the antihyperglycaemic mechanism of action of this traditionally used plant we also studied the activity of Coreopsis tinctoria flavonoids on the pancreatic function of glucose-intolerant rats. A standard antioxidant, Trolox, was also studied for comparative purposes as the antioxidant mechanism has been frequently purposed as one of the mechanisms mediating antihyperglycaemic effects of flavonoid-rich extracts. Thirteen compounds, mainly of flavanone and chalcone flavonoidal type, have been identified in this fraction by HPLC-DAD-ESI-MS/MS, and the major one (marein) quantified by HPLC-UV. The fraction (125 mg containing 20 mg of marein/kg b.w.) and Trolox (50 mg/kg b.w.) were administered daily by oral gavage to normal and STZ (40 mg/kg b.w.)-induced glucose-intolerant Wistar rats for 3 weeks. Blood glucose levels were measured weekly by Oral Glucose Tolerance Test. Pancreatic function was evaluated by plasma lipase of treated and non-treated glucose-tolerant and- intolerant rats after the 3-week treatment period. After 2 weeks oral treatment with Coreopsis tinctoria AcOEt fraction the animals were no longer glucose-intolerant, an effect maintained over the remaining experimental period. Additionally, plasma lipase values of glucose-intolerant animals treated with the AcOEt fraction (13.5 ± 0.84 U/L) showed a clear reduction when compared with the glucose-intolerant group (34.60 ± 1.76 U/L; P<0.001) and normoglycaemic control (8.35 ± 0.69 U/L) demonstrating recovery of pancreatic function. On the other hand, treatment with standard antioxidant Trolox had no effect on glucose homeostasis of glucose-intolerant rats. The oral treatment with Coreopsis tinctoria fraction caused no hepatotoxicity, as determined by blood alanine and aspartate transaminases, and had also no effect on glucose homeostasis and pancreatic function of normal rats. AcOEt fraction, containing the same amount of marein as the infusion, promoted glucose tolerance regain in the rats more quickly, which means that the bioactivity is probably due to the several flavonoids present in Coreopsis tinctoria extracts and not to marein alone. The results also strongly suggest that these compounds act by promoting pancreatic cell function recovery from STZ-induced injury, possibly through a mechanism of action other than merely antioxidant mediated. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses.

PubMed

Teff, Karen L; Grudziak, Joanne; Townsend, Raymond R; Dunn, Tamara N; Grant, Ryan W; Adams, Sean H; Keim, Nancy L; Cummings, Bethany P; Stanhope, Kimber L; Havel, Peter J

2009-05-01

Compared with glucose-sweetened beverages, consumption of fructose-sweetened beverages with meals elevates postprandial plasma triglycerides and lowers 24-h insulin and leptin profiles in normal-weight women. The effects of fructose, compared with glucose, ingestion on metabolic profiles in obese subjects has not been studied. The objective of the study was to compare the effects of fructose- and glucose-sweetened beverages consumed with meals on hormones and metabolic substrates in obese subjects. The study had a within-subject design conducted in the clinical and translational research center. Participants included 17 obese men (n = 9) and women (n = 8), with a body mass index greater than 30 kg/m(2). Subjects were studied under two conditions involving ingestion of mixed nutrient meals with either glucose-sweetened beverages or fructose-sweetened beverages. The beverages provided 30% of total kilocalories. Blood samples were collected over 24 h. Area under the curve (24 h AUC) for glucose, lactate, insulin, leptin, ghrelin, uric acid, triglycerides (TGs), and free fatty acids was measured. Compared with glucose-sweetened beverages, fructose consumption was associated with lower AUCs for insulin (1052.6 +/- 135.1 vs. 549.2 +/- 79.7 muU/ml per 23 h, P < 0.001) and leptin (151.9 +/- 22.7 vs. 107.0 +/- 15.0 ng/ml per 24 h, P < 0.03) and increased AUC for TG (242.3 +/- 96.8 vs. 704.3 +/- 124.4 mg/dl per 24 h, P < 0.0001). Insulin-resistant subjects exhibited larger 24-h TG profiles (P < 0.03). In obese subjects, consumption of fructose-sweetened beverages with meals was associated with less insulin secretion, blunted diurnal leptin profiles, and increased postprandial TG concentrations compared with glucose consumption. Increases of TGs were augmented in obese subjects with insulin resistance, suggesting that fructose consumption may exacerbate an already adverse metabolic profile present in many obese subjects.

Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro

PubMed Central

Lv, Zhimei; Hu, Mengsi; Ren, Xiaoxu; Fan, Minghua; Zhen, Junhui; Chen, Liqun; Lin, Jiangong; Ding, Nannan; Wang, Qun; Wang, Rong

2016-01-01

Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation. PMID:26881253

Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels across dementia staging in Alzheimer's disease: a clinical setting-based retrospective study.

PubMed

Ramdane, Said; Daoudi-Gueddah, Doria

2011-08-01

We examined retrospectively the concurrent relationships between fasting plasma total cholesterol, triglycerides, and glucose levels, and Alzheimer's disease (AD), in a clinical setting-based study. Total cholesterol level was higher in patients with AD compared to elderly controls; triglycerides or glucose levels did not significantly differ between the 2 groups. Respective plotted trajectories of change in cholesterol level across age were fairly parallel. No significant difference in total cholesterol levels was recorded between patients with AD classified by the Clinical Dementia Rating (CDR) score subgroups. These results suggest that patients with AD have relative mild total hypercholesterolemia, normal triglyceridemia, and normal fasting plasma glucose level. Mild total hypercholesterolemia seems to be permanent across age, and across dementia severity staging, and fairly parallels the trajectory of age-related change in total cholesterolemia of healthy controls. We speculate that these biochemical parameters pattern may be present long before-a decade at least-the symptomatic onset of the disease.

Immobilized glucose oxidase--catalase and their deactivation in a differential-bed loop reactor.

PubMed

Prenosil, J E

1979-01-01

Glucose oxidase containing catalase was immobilized with a copolymer of phenylenediamine and glutaraldehyde on pumice and titania carrier to study the enzymatic oxidation of glucose in a differential-bed loop reactor. The reaction rate was found to be first order with respect to the concentration of limiting oxygen substrate, suggesting a strong external mass-transfer resistance for all the flow rates used. The partial pressure of oxygen was varied from 21.3 up to 202.6 kPa. The use of a differential-bed loop reactor for the determination of the active enzyme concentration in the catalyst with negligible internal pore diffusion resistance is shown. Catalyst deactivation was studied, especially with respect to the presence of catalase. It is believed that the hydrogen peroxide formed in the oxidation reaction deactivates catalase first; if an excess of catalase is present, the deactivation of glucose oxidase remains small. The mathematical model subsequently developed adequately describes the experimental results.

Further optimization of culture method for rat keratinocytes: titration of glucose and sodium chloride.

PubMed

Oku, H; Yamashita, M; Iwasaki, H; Chinen, I

1999-02-01

The present study further improved the serum-free method of culturing rat keratinocytes. To obtain the best growth of rat keratinocytes, we modified our previous serum-free medium (MCDB153 based medium), particularly the amounts of glucose and sodium chloride (NaCl). Titration experiments showed the optimal concentration to be 0.8 mM for glucose and 100 mM for NaCl. This modification eliminated the requirement for albumin, which had been essential for colony formation when our previous medium was used. Titration of glucose and NaCl, followed by adjustment of essential amino acids and growth factors, produced a new formulation. More satisfactory and better growth was achieved with the new medium than with the previous medium. Accumulation of monoalkyldiacylglycerol (MADAG) was consistently noted in this study, representing the unusual lipid profile. A tendency toward normalization was, however, noted with the neutral lipid profile of keratinocytes cultivated in the new medium: lower production of MADAG was obtained with the new formulation, rather than the previous one.

Hyperglycaemia does not affect antigen-specific activation and cytolytic killing by CD8+ T cells in vivo.

PubMed

Recino, Asha; Barkan, Kerry; Wong, F Susan; Ladds, Graham; Cooke, Anne; Wallberg, Maja

2017-08-31

Metabolism is of central importance for T cell survival and differentiation. It is well known that T cells cannot function in the absence of glucose, but it is less clear how they respond to excessive levels of glucose. In the present study, we investigated how increasing levels of glucose affect T-cell-mediated immune responses. We examined the effects of increased levels of glucose on CD8 + T-cell behaviour in vitro by assessing activation and cytokine production, as well as oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and intracellular signalling. In addition, we assessed in vivo proliferation, cytokine production and cytolytic activity of cells in chemically induced diabetic C57BL/6 mice. Elevated levels of glucose in in vitro cultures had modest effects on proliferation and cytokine production, while in vivo hyperglycaemia had no effect on CD8 + T-cell proliferation, interferon γ (IFNγ) production or cytolytic killing. © 2017 The Author(s).

Electrochemical Performance of Glucose/Oxygen Biofuel Cells Based on Carbon Nanostructures.

PubMed

Koo, Min-Hye; Das, Gautam; Yoon, Hyon Hee

2016-03-01

The electrochemical performance of glucose/oxygen biofuel cells based on carbon nanostructures was investigated in the present study. Different types of carbon nanomaterials, including multi-walled carbon nanotubes (MWCNT), functionalized MWCNT (f-MWCNT), carbon nanofibers (CNF), and functionalized CNF (f-CNF) were examined for electrode fabrications. The anode for glucose/oxygen biofuel cells were prepared by sequential coating of carbon nanomaterials, charge transfer complex (CTC), glucose oxidase (GOx) and nafion membrane. The anode was then integrated with a bilirubin oxidase-immobilized cathode for the biofuel cell test. It was found that the electrochemical performance of the enzyme electrodes was remarkably enhanced by the amalgamation of carbon nanomaterials with the CTC. The biofuel cell with anode comprising of f-CNF and the cathode with MWCNT exhibited the best electrochemical performance with a maximum power density of 210 μW/cm2 at a cell voltage of 0.44 V for 20 mM glucose concentration, which is comparable with the best power density value reported earlier.

Effects of dietary traditional fermented soybean on reproductive hormones, lipids, and glucose among postmenopausal women in northern Thailand.

PubMed

Sapbamrer, Ratana; Visavarungroj, Nuwat; Suttajit, Maitree

2013-01-01

Isoflavone in soybean and its products have numerous beneficial health effects. A number of clinical studies have demonstrated that dietary soy isoflavone can relieve menopausal symptoms, lower risks of breast cancer, and lower cholesterol and glucose. Among the various effects of isoflavone, the role of cholesterol and glucose reduction seems to be well documented; however, other effects such as reproductive hormones were inconclusive and inconsistent. The main objective of the present study was to investigate the effects of six-month dietary traditional fermented soybean intake on BMI, reproductive hormones, lipids, and glucose among postmenopausal women. Subjects were women with their last menstrual period occurring at least 12 months prior to selection by interview and health screening from Baan Tham Village, Phayao Province, Thailand. A total of 60 women were divided into 2 groups: experimental group (n=31) and reference group (n=29). The experimental group was permitted to continue their usual diet, and supplemented with fermented soybean for 6 months. The fermented soybean provided approximately 60 mg of isoflavone per day. The remarkable findings were that dietary fermented soybean had favorable effects on progesterone and cholesterol, but had no effects on estradiol, glucose, and triglycerides. Although estradiol and glucose in the experimental group did not change, a decrease of estradiol and an increase of glucose were found in the reference group. Our results, therefore, suggest that fermented soybean may have beneficial effects on reproductive hormones and cholesterol, and they would be warrant further detail investigations.

Effect of GABA receptor agonists or antagonists injected spinally on the blood glucose level in mice.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

2013-05-01

The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.

[Monolayer culture of pancreatic islet cells of the adult rat: effect of 2-deoxy-2-fluoroglucose].

PubMed

Aoki, M; Kagawa, S; Yamamura, T; Matsuoka, A; Utsunomiya, J

1988-02-20

In the present study, the culture system for preparing monolayer islet cells of the neonatal rat was applied and modified for use with the pancreas of the adult rat. In this procedure, whole pancreatic tissues were enzymatically dispersed and then cultured for 30 days in TCM 199 medium with either 5.5 mM glucose or 5.5 mM glucose plus 1 mM 2-deoxy-2-fluoroglucose. Under culture conditions without 2-deoxy-2-fluoroglucose, the responsiveness of B cells was totally abolished by day 20 of culture. The addition of 2-deoxy-2-fluoroglucose destroyed fibroblasts selectively in a period of 20 days, yielding the monolayers mostly consisting of islet cells, and the morphological characteristics were well preserved at the end of the culture study period. After culture for 20 days in medium with 2-deoxy-2-fluoroglucose, insulin secretion was raised in a dose-dependent fashion due to the increasing concentrations of glucose, leucine and 2-ketoisocaproate. The dose-response curve for insulin secretion evoked by glucose was sigmoid with a Km of 7 mM glucose, and the secretion threshold was observed at a concentration of between 2.8 and 5.5 mM glucose. The ratios of the maximum level to the basal were 6, 5 and 3 respectively for glucose, leucine and 2-ketoisocaproate. The secretory competence was preserved in the B cells on day 30 as well. Addition of epinephrine or clonidine inhibited the glucose-induced insulin secretion dose-dependently. At a concentration of 10(-7) M, both drugs produced an 80% drop in insulin secretion evoked by glucose. The inhibitory effect of epinephrine or clonidine was reversed by 3 X 10(-5) M yohimbine or 10(-5) M phentolamine, whereas 10(-5) M propranolol had little or no effect and alpha adrenergic blockade of prazosin (5 X 10(-5) M) was weak as compared to that of yohimbine. At a high concentration (10(-5) M) of phenylephrine, a marked drop of insulin secretion was observed. In summary, the present culture system facilitates the establishment of monolayers of adult rat pancreas that consist mostly of islet cells. In addition, it is certain that the response of the B cells in 2-deoxy-2-fluoroglucose to nutrient secretagogues and the adrenergic modulation of insulin secretion are well preserved for a long-term culture period of 30 days. These preparations may provide a useful tool not only for the in vitro study of the B-cell function, but also for use in implantation resource.

Testing the Glucose Hypothesis among Capuchin Monkeys: Does Glucose Boost Self-Control?

PubMed

Parrish, Audrey E; Emerson, Ishara D; Rossettie, Mattea S; Beran, Michael J

2016-08-03

The ego-depletion hypothesis states that self-control diminishes over time and with exertion. Accordingly, the glucose hypothesis attributes this depletion of self-control resources to decreases in blood glucose levels. Research has led to mixed findings among humans and nonhuman animals, with limited evidence for such a link between glucose and self-control among closely-related nonhuman primate species, but some evidence from more distantly related species (e.g., honeybees and dogs). We tested this hypothesis in capuchin monkeys by manipulating the sugar content of a calorie-matched breakfast meal following a nocturnal fast, and then presenting each monkey with the accumulation self-control task. Monkeys were presented with food items one-by-one until the subject retrieved and ate the accumulating items, which required continual inhibition of food retrieval in the face of an increasingly desirable reward. Results indicated no relationship between self-control performance on the accumulation task and glucose ingestion levels following a fast. These results do not provide support for the glucose hypothesis of self-control among capuchin monkeys within the presented paradigm. Further research assessing self-control and its physiological correlates among closely- and distantly-related species is warranted to shed light on the mechanisms underlying self-control behavior.

[Insulin-glucose ratio and body fat composition in patients with chronic anovulation and sterility].

PubMed

Vital Reyes, V S; Enríquez Miranda, M C; Martínez Martínez, E; Coronel, M C; Hinojosa Cruz, J C; Téllez Velasco, S

2002-02-01

A clinical, descriptive, and transversal study was conducted in a group of patients with chronic anovulation and sterility, to correlate insulin resistance, determined by the fasting glucose/insulin ratio, with body fat composition using anthropometrics parameters and the interaction of light near infrared region method, we studied 41 young patients with chronic anovulation and sterility. Based on their body mass index, all patients had obesity or overweight. Similarly, most of them presented with a percentage of body fat over the recommended limits. Forty percent of all studied patients had a fasting glucose/insulin ratio below 4.5, which corresponds to insulin resistance. The correlation between the percentage of body fat and fasting glucose/insulin ratio was significant, as was the correlation between body mass index and the percentage of body fat. We found overweight or obesity in the majority of our patients, and insulin resistance in almost half of them. Such disturbances were positively associated with the percentage of body fat and android distribution. Therefore, we recommend a routinely anthropometrics evaluation in these patients as well as fasting glucose/insulin ratio determination in order to act in an early stage over the natural history of metabolic syndrome, whose common denominator is insulin resistance.

The regulatory effects of resistant starch on glycaemic response in obese dogs.

PubMed

Kimura, Tohru

2013-12-01

The purpose of this study was to examine the inhibitory effects of resistant starch on postprandial glycaemic response in obese dogs. The changes in blood glucose concentrations and glycaemic index (GI) were chronologically determined after the administration of resistant and normal starches by nasal feeding. Resistant starch contained indigestible dextrin (IDD) and β-cyclic dextrin (β-CD). Soluble starch (SS) served as a control starch. Glucose concentrations reached their maximum 15 min after the administration of SS solutions, and decreased gradually during the experimental period. In contrast, after the administration of IDD solutions, increased glucose concentrations rapidly decreased to the initial values. After the administration of β-CD solutions, glucose concentrations remained unchanged during this study. GI levels remained constant in the following order: β-CD < IDD < SS. GI levels of dogs receiving IDD and β-CD solutions were significantly lower as compared with those animals receiving SS solutions. In this study, nasal tube feeding was an effective method for evaluating glycaemic responses to various starches accurately. The present data revealed that resistant starches were useful materials in controlling nutritionally glucose concentrations in obese dogs. These results raise the possibility that resistant starches are valuable for dietetic treatment of diabetes and obesity in dogs.

Can gingival crevicular blood be relied upon for assessment of blood glucose level?

PubMed

Dwivedi, Shivani; Verma, Sharmila J; Shah, Monali; Jain, Kapil

2014-11-01

Diabetes mellitus (DM) is undiagnosed in approximately half of the patients actually suffering from the disease. In addition, the prevalence of DM is more than twice as high as in patients with periodontitis when compared to periodontally healthy subjects. Thus, a high number of patients with periodontitis may have undiagnosed DM. The purpose of the present study was to evaluate whether blood oozing from a gingival crevice during routine periodontal examination can be used for determining glucose levels. Observational cross-sectional studies were carried out in 75 patients (43 males and 32 females) with chronic periodontitis who were divided into two groups: Group I and Group II, respectively. Blood oozing from the gingival crevices of anterior teeth following periodontal probing was collected with the stick of glucose self-monitoring device, and the blood glucose levels were measured. At the same time, finger-prick blood was taken for glucometric analysis and subsequent readings were recorded. The patient's blood glucose values ranged from 74 to 256 mg/dl. The comparison between gingival crevicular blood and finger-prick blood showed a very strong correlation, with a t value of 3.97 (at P value = 0.001). The data from this study has shown that GCB collected during diagnostic periodontal examination can be an excellent source of blood for glucometric analysis.

Relative contribution of muscle and liver insulin resistance to dysglycemia in postmenopausal overweight and obese women: A MONET group study.

PubMed

Elisha, Belinda; Disse, Emmanuel; Chabot, Katherine; Taleb, Nadine; Prud'homme, Denis; Bernard, Sophie; Rabasa-Lhoret, Rémi; Bastard, Jean-Philippe

2017-02-01

The relative contribution of muscle and liver insulin resistance (IR) in the development of dysglycemia and metabolic abnormalities is difficult to establish. The present study aimed to investigate the relative contribution of muscle IR vs. liver IR to dysglycemia in non-diabetic overweight or obese postmenopausal women and to determine differences in body composition and cardiometabolic indicators associated with hepatic or muscle IR. Secondary analysis of 156 non-diabetic overweight or obese postmenopausal women. Glucose tolerance was measured using an oral glucose tolerance test. Whole-body insulin sensitivity (IS) was determined as glucose disposal rate during a euglycemic-hyperinsulinemic clamp. Muscle and liver IR have been calculated using Abdul-Ghani et al. OGTT-derived formulas. Participant's body compositions as well as cardiometabolic risk indicators were also determined. Overall, 57 (36.5%) of patients had dysglycemia, among them 25 (16.0%); 21 (13.5%); 11 (7.1%) had impaired fasting glycemia, impaired glucose tolerance and combined glucose intolerance respectively. Fifty-three (34.0%) participants were classified as combined IS while on the opposite 51 participants (32.7%) were classified as combined IR and 26 (16.7%) participants had either muscle IR or liver IR. For similar body mass index and total fat mass, participants with liver IR were more likely to have lower whole-body IS, dysglycemia and higher visceral fat, liver fat index, triglycerides and alanine aminotransferase than participants with muscle IR. In the present study, the presence of liver IR is associated with a higher prevalence of dysglycemia, ectopic fat accumulation and metabolic abnormalities than muscle IR. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Novel nutraceutic therapies for the treatment of metabolic syndrome

PubMed Central

Martínez-Abundis, Esperanza; Méndez-del Villar, Miriam; Pérez-Rubio, Karina G; Zuñiga, Laura Y; Cortez-Navarrete, Marisol; Ramírez-Rodriguez, Alejandra; González-Ortiz, Manuel

2016-01-01

Nutraceutic therapies such as berberine, bitter melon, Gymnema sylvestre, Irvingia gabonensis, resveratrol and ursolic acid have been shown to help control metabolic syndrome (MetS). The effect of berberine on glucose and lipid metabolism, hypertension, obesity and MetS has been evaluated in animal models and humans. Most clinical trials involving bitter melon have been conducted to evaluate its effect on glucose metabolism; nevertheless, some studies have reported favorable effects on lipids and blood pressure although there is little information about its effect on body weight. Gymnema sylvestre helps to decrease body weight and blood sugar levels; however, there is limited information on dyslipidemia and hypertension. Clinical trials of Irvingia gabonensis have shown important effects decreasing glucose and cholesterol concentrations as well decreasing body weight. Resveratrol acts through different mechanisms to decrease blood pressure, lipids, glucose and weight, showing its effects on the population with MetS. Finally, there is evidence of positive effects with ursolic acid in in vitro and in vivo studies on glucose and lipid metabolism and on body weight and visceral fat. Therefore, a review of the beneficial effects and limitations of the above-mentioned nutraceutic therapies is presented. PMID:27076875

Insulin Resistance and Mitochondrial Dysfunction.

PubMed

Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

2017-01-01

Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

Oral glucose tolerance test significantly impacts the prevalence of abnormal glucose tolerance among Indian women with polycystic ovary syndrome: lessons from a large database of two tertiary care centers on the Indian subcontinent.

PubMed

Ganie, Mohd Ashraf; Dhingra, Atul; Nisar, Sobia; Sreenivas, Vishnubhatla; Shah, Zaffar Amin; Rashid, Aafia; Masoodi, Shariq; Gupta, Nandita

2016-01-01

To estimate the prevalence of abnormal glucose tolerance (AGT) among Indian women with polycystic ovary syndrome (PCOS) and analyze the role of oral glucose tolerance (OGTT) test on its estimation. Cross-sectional clinical study. Tertiary care center. A total of 2,014 women with PCOS diagnosed on the basis of the Rotterdam 2003 criteria were enrolled, and the data of 1,746 subjects were analyzed. In addition to recording clinical, biochemical, and hormone parameters, a 75 g OGTT was administered. Prevalence of AGT and impact of age, body mass index (BMI), family history, and OGTT on its prevalence. The mean age of subjects was 23.8 ± 5.3 years, with a mean BMI of 24.9 ± 4.4 kg/m(2). The overall prevalence of AGT was 36.3% (6.3% diabetes and 30% impaired fasting plasma glucose/impaired glucose tolerance) using American Diabetes Association criteria. The glucose intolerance showed a rising trend with advancing age (30.3%, 35.4%, 51%, and 58.8% in the second, third, fourth, and fifth decades, respectively) and increasing BMI. Family history of diabetes mellitus was present in 54.6% (953/1,746) subjects, and it did not correlate with any of the studied parameters except waist circumference and BMI. Sensitivity was better with 2-hour post-OGTT glucose values as compared with fasting plasma glucose, since using fasting plasma glucose alone would have missed the diagnosis in 107 (6.1%) subjects. We conclude that AGT is high among young Indian women with PCOS and that it is not predicted by family history of type 2 DM. OGTT significantly improves the detection rate of AGT among Indian women with PCOS. Copyright © 2016. Published by Elsevier Inc.

Regulation of xylose metabolism in recombinant Saccharomyces cerevisiae

PubMed Central

Salusjärvi, Laura; Kankainen, Matti; Soliymani, Rabah; Pitkänen, Juha-Pekka; Penttilä, Merja; Ruohonen, Laura

2008-01-01

Background Considerable interest in the bioconversion of lignocellulosic biomass into ethanol has led to metabolic engineering of Saccharomyces cerevisiae for fermentation of xylose. In the present study, the transcriptome and proteome of recombinant, xylose-utilising S. cerevisiae grown in aerobic batch cultures on xylose were compared with those of glucose-grown cells both in glucose repressed and derepressed states. The aim was to study at the genome-wide level how signalling and carbon catabolite repression differ in cells grown on either glucose or xylose. The more detailed knowledge whether xylose is sensed as a fermentable carbon source, capable of catabolite repression like glucose, or is rather recognised as a non-fermentable carbon source is important for further engineering this yeast for more efficient anaerobic fermentation of xylose. Results Genes encoding respiratory proteins, proteins of the tricarboxylic acid and glyoxylate cycles, and gluconeogenesis were only partially repressed by xylose, similar to the genes encoding their transcriptional regulators HAP4, CAT8 and SIP1-2 and 4. Several genes that are repressed via the Snf1p/Mig1p-pathway during growth on glucose had higher expression in the cells grown on xylose than in the glucose repressed cells but lower than in the glucose derepressed cells. The observed expression profiles of the transcription repressor RGT1 and its target genes HXT2-3, encoding hexose transporters suggested that extracellular xylose was sensed by the glucose sensors Rgt2p and Snf3p. Proteome analyses revealed distinct patterns in phosphorylation of hexokinase 2, glucokinase and enolase isoenzymes in the xylose- and glucose-grown cells. Conclusion The results indicate that the metabolism of yeast growing on xylose corresponds neither to that of fully glucose repressed cells nor that of derepressed cells. This may be one of the major reasons for the suboptimal fermentation of xylose by recombinant S. cerevisiae strains. Phosphorylation of different isoforms of glycolytic enzymes suggests that regulation of glycolysis also occurred at a post-translational level, supporting prior findings. PMID:18533012

Transgenerational changes of metabolic phenotypes in two selectively bred mouse colonies for different susceptibilities to diet-induced glucose intolerance.

PubMed

Nagao, Mototsugu; Asai, Akira; Sugihara, Hitoshi; Oikawa, Shinichi

2015-01-01

We recently established 2 mouse lines with different susceptibilities (prone and resistant) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-prone [SDG-P] and -resistant [SDG-R], respectively). In the present study, we analyzed transgenerational changes in metabolic phenotypes in these 2 mouse colonies to explore how the distinct phenotypes have emerged through the repetitive selection. Using C57BL/6, C3H, and AKR as background strains, mice showing inferior and superior glucose tolerance after HFD feeding were selected and bred repetitively over 20 generations to produce SDG-P and SDG-R, respectively. In addition to the blood glucose levels, HFD intake and body weight were also measured over the selective breeding period. As the generations proceeded, SDG-P mice became more susceptible to HFD-induced glucose intolerance and body weight gain, whereas SDG-R mice had gradually reduced HFD intake. The differences in fasting and post-glucose challenge blood glucose levels, body weight, and HFD intake became more evident between the 2 colonies through the selective breeding, mainly due to the HFD-induced glucose metabolism impairment and body weight gain in SDG-P mice and the reduction of HFD intake in SDG-R mice. These transgenerational changes in the metabolic phenotypes suggest that the genetic loci associated with the quantitative traits have been selectively enriched in SDG-P and SDG-R.

Gibbs Free-Energy Gradient along the Path of Glucose Transport through Human Glucose Transporter 3.

PubMed

Liang, Huiyun; Bourdon, Allen K; Chen, Liao Y; Phelix, Clyde F; Perry, George

2018-06-11

Fourteen glucose transporters (GLUTs) play essential roles in human physiology by facilitating glucose diffusion across the cell membrane. Due to its central role in the energy metabolism of the central nervous system, GLUT3 has been thoroughly investigated. However, the Gibbs free-energy gradient (what drives the facilitated diffusion of glucose) has not been mapped out along the transport path. Some fundamental questions remain. Here we present a molecular dynamics study of GLUT3 embedded in a lipid bilayer to quantify the free-energy profile along the entire transport path of attracting a β-d-glucose from the interstitium to the inside of GLUT3 and, from there, releasing it to the cytoplasm by Arrhenius thermal activation. From the free-energy profile, we elucidate the unique Michaelis-Menten characteristics of GLUT3, low K M and high V MAX , specifically suitable for neurons' high and constant demand of energy from their low-glucose environments. We compute GLUT3's binding free energy for β-d-glucose to be -4.6 kcal/mol in agreement with the experimental value of -4.4 kcal/mol ( K M = 1.4 mM). We also compute the hydration energy of β-d-glucose, -18.0 kcal/mol vs the experimental data, -17.8 kcal/mol. In this, we establish a dynamics-based connection from GLUT3's crystal structure to its cellular thermodynamics with quantitative accuracy. We predict equal Arrhenius barriers for glucose uptake and efflux through GLUT3 to be tested in future experiments.

Pyruvate incubation enhances glycogen stores and sustains neuronal function during subsequent glucose deprivation.

PubMed

Shetty, Pavan K; Sadgrove, Matthew P; Galeffi, Francesca; Turner, Dennis A

2012-01-01

The use of energy substrates, such as lactate and pyruvate, has been shown to improve synaptic function when administered during glucose deprivation. In the present study, we investigated whether prolonged incubation with monocarboxylate (pyruvate or lactate) prior rather than during glucose deprivation can also sustain synaptic and metabolic function. Pyruvate pre-incubation(3-4h) significantly prolonged (>25 min) the tolerance of rat hippocampal slices to delayed glucose deprivation compared to control and lactate pre-incubated slices, as revealed by field excitatory post synaptic potentials (fEPSPs); pre-incubation with pyruvate also reduced the marked decrease in NAD(P)H fluorescence resulting from glucose deprivation. Moreover, pyruvate exposure led to the enhancement of glycogen stores with time, compared to glucose alone (12 μmol/g tissue at 4h vs. 3.5 μmol/g tissue). Prolonged resistance to glucose deprivation following exogenous pyruvate incubation was prevented by glycogenolysis inhibitors, suggesting that enhanced glycogen mediates the delay in synaptic activity failure. The application of an adenosine A1 receptor antagonist enhanced glycogen utilization and prolonged the time to synaptic failure, further confirming this hypothesis of the importance of glycogen. Moreover, tissue levels of ATP were also significantly maintained during glucose deprivation in pyruvate pretreated slices compared to control and lactate. In summary, these experiments indicate that pyruvate exposure prior to glucose deprivation significantly increased the energy buffering capacity of hippocampal slices, particularly by enhancing internal glycogen stores, delaying synaptic failure during glucose deprivation by maintaining ATP levels, and minimizing the decrease in the levels of NAD(P)H. Copyright © 2011 Elsevier Inc. All rights reserved.

Apelin targets gut contraction to control glucose metabolism via the brain

PubMed Central

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-01-01

Objective The gut–brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. Design We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. Results In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. PMID:26565000

In vivo glucose monitoring using dual-wavelength polarimetry to overcome corneal birefringence in the presence of motion.

PubMed

Pirnstill, Casey W; Malik, Bilal H; Gresham, Vincent C; Coté, Gerard L

2012-09-01

Over the past 35 years considerable research has been performed toward the investigation of noninvasive and minimally invasive glucose monitoring techniques. Optical polarimetry is one noninvasive technique that has shown promise as a means to ascertain blood glucose levels through measuring the glucose concentrations in the anterior chamber of the eye. However, one of the key limitations to the use of optical polarimetry as a means to noninvasively measure glucose levels is the presence of sample noise caused by motion-induced time-varying corneal birefringence. In this article our group presents, for the first time, results that show dual-wavelength polarimetry can be used to accurately detect glucose concentrations in the presence of motion-induced birefringence in vivo using New Zealand White rabbits. In total, nine animal studies (three New Zealand White rabbits across three separate days) were conducted. Using the dual-wavelength optical polarimetric approach, in vivo, an overall mean average relative difference of 4.49% (11.66 mg/dL) was achieved with 100% Zone A+B hits on a Clarke error grid, including 100% falling in Zone A. The results indicate that dual-wavelength polarimetry can effectively be used to significantly reduce the noise due to time-varying corneal birefringence in vivo, allowing the accurate measurement of glucose concentration in the aqueous humor of the eye and correlating that with blood glucose.

Short-term and long-term effects of guar on postprandial plasma glucose, insulin and glucagon-like peptide 1 concentration in healthy rats.

PubMed

Prieto, P G; Cancelas, J; Villanueva-Peñacarrillo, M L; Malaisse, W J; Valverde, I

2006-06-01

Ingestion of guar gum decreases postprandial glycemia and insulinemia and improves sensitivity to insulin in diabetic patients and several animal models of diabetes. The aim of the present study was to compare the short-term and long-term effects of guar on plasma insulin and glucagon-like peptide 1 concentration in healthy rats. In the short-term experiments, the concomitant intragastric administration of glucose and guar reduced the early increment in plasma glucose, insulin and glucagon-like peptide 1 concentration otherwise induced by glucose alone. Comparable findings were made after twelve days of meal training exposing the rats to either a control or guar-enriched diet for fifteen minutes. Mean plasma glucose concentrations were lower while mean insulin concentrations were higher in the guar group than in the controls according to intragastric glucose tolerance tests conducted in overnight fasted rats maintained for 19 to 36 days on either the control or guar-enriched diet. The intestinal content of glucagon-like peptide 1 at the end of the experiments was also lower in the guar group. Changes in body weight over 62 days of observation were comparable in the control and guar rats. Thus, long-term intake of guar improves glucose tolerance and insulin response to glucose absorption, without improving insulin sensitivity, in healthy rats.

The association of plasma glucose, BHBA, and NEFA with postpartum uterine diseases, fertility, and milk production of Holstein dairy cows.

PubMed

Bicalho, M L S; Marques, E C; Gilbert, R O; Bicalho, R C

2017-01-15

The objective of this study was to investigate the association between the metabolic indicators such as nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and glucose during the transition period and the development of uterine diseases. In total, 181 Holstein dairy cows were enrolled in the study. Plasma glucose, NEFA, and BHBA concentrations were measured at -50, -6, 3, 7, and 14 days relative to parturition. All cows enrolled in the study were evaluated for retained placenta (RP), metritis, and endometritis. Metritis and RP were diagnosed and treated by trained farm personnel. Clinical endometritis was evaluated by a veterinarian at 35 days in milk using a Metricheck device. We found plasma glucose concentration to be associated with the occurrence of metritis and clinical endometritis. Moreover, cows with an increased calving-to-conception interval (>150 days) presented higher plasma glucose concentrations than cows that became pregnant within the first 150 days, whereas BHBA and NEFA were not associated with the occurrence of any uterine disorder. Receiver operating characteristic (ROC) curves were used in an attempt to determine the cow-level critical thresholds for the occurrence of metritis, and endometritis. In addition, pairwise comparisons of area under the curve (AUC) of ROC curves for the critical thresholds for glucose, BHBA, and NEFA predicting the same uterine disease were performed. Glucose at 3 days in milk was the best predictor for metritis and endometritis diagnosis, with AUC values of 0.66 and 0.67, respectively. Multivariable logistic regressions were performed and showed that cows with higher levels of glucose at Day 3 were at 6.6 times higher odds of being diagnosed with metritis, and 3.5 times higher odds of developing clinical endometritis, compared with cows with lower glucose levels. Finally, a simple linear regression analysis demonstrated a negative correlation between daily milk yield in the first and second weeks of lactation and plasma glucose concentrations measured at Days 7 and 14, respectively. Concentrations of NEFA and BHBA were not found to be associated with milk production. Copyright © 2016 Elsevier Inc. All rights reserved.

Glucose metabolism in gastric cancer: The cutting-edge

PubMed Central

Yuan, Lian-Wen; Yamashita, Hiroharu; Seto, Yasuyuki

2016-01-01

Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer. PMID:26877609

Euglycemic Diabetic Ketoacidosis with Elevated Acetone in a Patient Taking a Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor.

PubMed

Andrews, Tory J; Cox, Robert D; Parker, Christina; Kolb, James

2017-02-01

Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose > 500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. Acetone is one of the three main ketone bodies formed during DKA and it may be present at considerable concentrations, contributing to the serum osmolality. Copyright © 2016 Elsevier Inc. All rights reserved.

Interstitial fluid glucose dynamics during insulin-induced hypoglycaemia.

PubMed

Steil, G M; Rebrin, K; Hariri, F; Jinagonda, S; Tadros, S; Darwin, C; Saad, M F

2005-09-01

Glucose sensors often measure s.c. interstitial fluid (ISF) glucose rather than blood or plasma glucose. Putative differences between plasma and ISF glucose include a protracted delay during the recovery from hypoglycaemia and an increased gradient during hyperinsulinaemia. These have often been investigated using sensor systems that have delays due to signal smoothing, or require long equilibration times. The aim of the present study was to define these relationships during hypoglycaemia in a well-equilibrated system with no smoothing. Hypoglycaemia was induced by i.v. insulin infusion (360 pmol.m(-2).min(-1)) in ten non-diabetic subjects. Glucose was sequentially clamped at approximately 5, 4.2 and 3.1 mmol/l and allowed to return to normoglycaemia. Subjects wore two s.c. glucose sensors (Medtronic MiniMed, Northridge, CA, USA) that had been inserted for more than 12 h. A two-compartment model was used to quantify the delay and gradient. The delay during the fall in plasma glucose was not different from the delay during recovery (8.3+/-0.67 vs 6.3+/-1.1 min; p=0.27) and no differences were observed in the ratio of sensor current to plasma glucose at basal insulin (2.7+/-0.25 nA.mmol(-1).l) compared with any of the hyperinsulinaemic clamp phases (2.8+/-0.18, 2.7+/-0.021, 2.9+/-0.21; p=NS). The ratio was significantly elevated following recovery to normoglycaemia (3.1+/-0.2 nA.mmol(-1).l; p<0.001). The elevated ratio suggests that the plasma to ISF glucose gradient was decreased following hypoglycaemia, possibly due to increased skin blood flow. Recovery from hypoglycaemia is not accompanied by a protracted delay and insulin does not increase the plasma to s.c. ISF glucose gradient.

Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but not lactate correlates positively with Ca2+ signalling in cultured mouse glutamatergic neurons

PubMed Central

Bak, Lasse K.; Obel, Linea F.; Walls, Anne B.; Schousboe, Arne; Faek, Sevan A.A.; Jajo, Farah S.; Waagepetersen, Helle S.

2012-01-01

We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate–aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca2+ signalling. PMID:22385215

Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but not lactate correlates positively with Ca2+ signalling in cultured mouse glutamatergic neurons.

PubMed

Bak, Lasse K; Obel, Linea F; Walls, Anne B; Schousboe, Arne; Faek, Sevan A A; Jajo, Farah S; Waagepetersen, Helle S

2012-04-05

We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate-aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca2+ signalling.

Blood glucose regulation mechanism in depressive disorder animal model during hyperglycemic states.

PubMed

Lim, Su-Min; Park, Soo-Hyun; Sharma, Naveen; Kim, Sung-Su; Lee, Jae-Ryeong; Jung, Jun-Sub; Suh, Hong-Won

2016-06-01

Depression is more common among diabetes people than in the general population. In the present study, blood glucose change in depression animal model was characterized by various types of hyperglycemia models such as d-glucose-fed-, immobilization stress-, and drug-induced hyperglycemia models. First, the ICR mice were enforced into chronic restraint stress for 2h daily for 2 weeks to produce depression animal model. The animals were fed with d-glucose (2g/kg), forced into restraint stress for 30min, or administered with clonidine (5μg/5μl) supraspinally or spinally to produce hyperglycemia. The blood glucose level in depression group was down-regulated compared to that observed in the normal group in d-glucose-fed-, restraint stress-, and clonidine-induced hyperglycemia models. The up-regulated corticosterone level induced by d-glucose feeding or restraint stress was reduced in the depression group while the up-regulation of plasma corticosterone level is further elevated after i.t. or i.c.v. clonidine administration in the depression group. The up-regulated insulin level induced by d-glucose feeding or restraint stress was reduced in the depression group. On the other hand, blood corticosterone level in depression group was up-regulated compared to the normal group after i.t. or i.c.v. clonidine administration. Whereas the insulin level in depression group was not altered when mice were administered clonidine i.t. or i.c.v. Our results suggest that the blood glucose level in depression group is down-regulated compared to the normal group during d-glucose-fed-, immobilization stress-, and clonidine-induced hyperglycemia in mice. The down-regulation of the blood glucose level might be one of the important pathophysiologic changes in depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells.

PubMed

Hamano, Kunihisa; Nakagawa, Yuko; Ohtsu, Yoshiaki; Li, Longfei; Medina, Johan; Tanaka, Yuji; Masuda, Katsuyoshi; Komatsu, Mitsuhisa; Kojima, Itaru

2015-07-01

Glucose activates the glucose-sensing receptor T1R3 and facilitates its own metabolism in pancreatic β-cells. An inhibitor of this receptor would be helpful in elucidating the physiological function of the glucose-sensing receptor. The present study was conducted to examine whether or not lactisole can be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose-dependent manner, lactisole inhibited insulin secretion induced by sweeteners, acesulfame-K, sucralose and glycyrrhizin. The IC50 was ∼4 mmol/l. Lactisole attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) evoked by sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP concentration ([cAMP]c) induced by these sweeteners. Lactisole also inhibited the action of glucose in MIN6 cells. Thus, lactisole significantly reduced elevations of intracellular [NADH] and intracellular [ATP] induced by glucose, and also inhibited glucose-induced insulin secretion. To further examine the effect of lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In these cells, sucralose elevated both [Ca2+]c and [cAMP]c. Lactisole attenuated the sucralose-induced increase in [Ca2+]c but did not affect the elevation of [cAMP]c. Finally, lactisole inhibited insulin secretion induced by a high concentration of glucose in mouse islets. These results indicate that the mouse glucose-sensing receptor was inhibited by lactisole. Lactisole may be useful in assessing the role of the glucose-sensing receptor in mouse pancreatic β-cells. © 2015 Society for Endocrinology.

Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil)

PubMed Central

Yarmolinsky, James; Mueller, Noel T.; Duncan, Bruce B.; Bisi Molina, Maria del Carmen; Goulart, Alessandra C.; Schmidt, Maria Inês

2015-01-01

Introduction Observational studies have reported fairly consistent inverse associations between coffee consumption and risk of type 2 diabetes, but this association has been little investigated with regard to lesser degrees of hyperglycemia and other alterations in glucose homeostasis. Additionally, the association between coffee consumption and diabetes has been rarely investigated in South American populations. We examined the cross-sectional relationships of coffee intake with newly diagnosed diabetes and measures of glucose homeostasis, insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle-aged and elderly individuals. Methods We used baseline data from 12,586 participants of the Longitudinal Study of Adult Health (ELSA-Brasil). Logistic regression analyses were performed to examine associations between coffee consumption and newly diagnosed diabetes. Analysis of covariance was used to assess coffee intake in relation to two-hour glucose from an oral glucose tolerance test, fasting glucose, glycated hemoglobin, fasting and –2-hour postload insulin and measures of insulin sensitivity. Results We found an inverse association between coffee consumption and newly diagnosed diabetes, after adjusting for multiple covariates [23% and 26% lower odds of diabetes for those consuming coffee 2–3 and >3 times per day, respectively, compared to those reporting never or almost never consuming coffee, (p = .02)]. An inverse association was also found for 2-hour postload glucose [Never/almost never: 7.57 mmol/L, ≤1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12 mol/L, p<0.0001] but not with fasting glucose concentrations (p = 0.07). Coffee was additionally associated with 2-hour postload insulin [Never/almost never: 287.2 pmol/L, ≤1 time/day: 280.1 pmol/L, 2–3 times/day: 275.3 pmol/L, >3 times/day: 262.2 pmol/L, p = 0.0005) but not with fasting insulin concentrations (p = .58). Conclusion Our present study provides further evidence of a protective effect of coffee on risk of adult-onset diabetes. This effect appears to act primarily, if not exclusively, through postprandial, as opposed to fasting, glucose homeostasis. PMID:25978631

Starch-entrapped biopolymer microspheres as a novel approach to vary blood glucose profiles.

PubMed

Venkatachalam, Mahesh; Kushnick, Michael R; Zhang, Genyi; Hamaker, Bruce R

2009-10-01

With emerging knowledge of the impact of the metabolic quality of glycemic carbohydrates on human health, there is a need for novel carbohydrate ingredients that can be custom-made to deliver controlled amounts of glucose to the body and to test hypotheses on the postprandial metabolic consequences of carbohydrates. The goal of the present study was to demonstrate the applicability and action of starch-entrapped biopolymer microspheres as customized, novel, slowly digestible carbohydrates to obtain desired glycemic responses. Starch-entrapped microspheres were developed; and starch digestion and glucose release, subsequent to their cooking (100 degrees C, 20 min) in water, were initially monitored by measuring the rapidly digestible, slowly digestible, and resistant starch fractions using the in vitro Englyst assay. Glycemic and insulinemic responses after consumption of glucose and two different slowly digestible starch microsphere diets were compared using a crossover study in 10 healthy individuals. The mechanism of starch digestion in the microspheres was elucidated from scanning electron microscopic images of the in vitro digested microspheres. Factors such as biopolymer type and concentration, microsphere size, and starch type were manipulated to obtain starch materials with defined amounts of slowly digestible starch based on in vitro studies. Scanning electron microscopy showed that cooked starch entrapped in the dense biopolymer matrix is digested layer by layer from the outside to the inside of the microsphere. Glycemic and insulinemic responses to microsphere test diets were moderate as compared to a glucose diet, but more important, they showed extended glucose release. Starch-entrapped microspheres provide a useful tool to study the postprandial metabolic consequences of slowly digestible carbohydrates.

Brain glucose content in fetuses of ethanol-fed rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pullen, G.; Singh, S.P.; Snyder, A.K.

1986-03-01

The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4more » and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.« less

Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hu, Fanghao; Chen, Zhixing; Zhang, Luyuan; Shen, Yihui; Wei, Lu; Min, Wei

2016-03-01

Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.

The proposed biosynthesis of procyanidins by the comparative chemical analysis of five Camellia species using LC-MS

PubMed Central

Zhang, Liang; Tai, Yuling; Wang, Yijun; Meng, Qilu; Yang, Yunqiu; Zhang, Shihua; Yang, Hua; Zhang, Zhengzhu; Li, Daxiang; Wan, Xiaochun

2017-01-01

The genus Camellia (C.) contains many species, including C. sinensis, C. assamica, and C. taliensis, C. gymnogyna and C. tachangensis. The polyphenols of C. sinensis and C. assamica are flavan-3-ols monomers and their dimers and trimmers. However, the biosynthesis of procyanidins in Camellia genus remains unclear. In the present study, a comparative chemical analysis of flavan-3-ols, flavan-3-ols glycoside and procyanidins was conducted by high performance liquid chromatography (HPLC) and liquid chromatography diode array detection coupled with triple-quadrupole mass-spectrometry (LC-DAD-QQQ-MS). The results showed that C. tachangensis had a significant higher contents of (-)-epicatechin (EC) and (-)-epigallocatechin (EGC) compared with C. sinensis (p < 0.001). By contrast, higher levels of galloylated catechins were detected in C. sinensis. LC-DAD-MS/MS indicated that the main secondary metabolites of C. tachangensis were non-galloylated catechins, procyanidin dimers and trimers. Furthermore, (-)-epicatechin glucose (EC-glucose) and (-)-epigallocatechin glucose (EGC-glucose) were also abundant in C. tachangensis. A correlation analysis of EC-glucose and procyanidins dimers was conducted in five Camellia species. The levels of EC-glucose were closely related to the procyanidin dimers content. Thus, it was suggested that EC-glucose might be an important substrate for the biosynthesis of procyanidins. PMID:28383067

Glycolytic and mitochondrial metabolism in pancreatic islets from MSG-treated obese rats subjected to swimming training.

PubMed

Leite, Nayara de Carvalho; Ferreira, Thiago Rentz; Rickli, Sarah; Borck, Patricia Cristine; Mathias, Paulo Cezar de Freitas; Emilio, Henriette Rosa de Oliveira; Grassiolli, Sabrina

2013-01-01

Obese rats obtained by neonatal monosodium glutamate (MSG) administration present insulin hypersecretion. The metabolic mechanism by which glucose catabolism is coupled to insulin secretion in the pancreatic β-cells from MSG-treated rats is understood. The purpose of this study was to evaluate glucose metabolism in pancreatic islets from MSG-treated rats subjected to swimming training. MSG-treated and control (CON) rats swam for 30 minutes (3 times/week) over a period of 10 weeks. Pancreatic islets were isolated and incubated with glucose in the presence of glycolytic or mitochondrial inhibitors. Swimming training attenuated fat pad accumulation, avoiding changes in the plasma levels of lipids, glucose and insulin in MSG-treated rats. Adipocyte and islet hypertrophy observed in MSG-treated rats were attenuated by exercise. Pancreatic islets from MSG-treated obese rats also showed insulin hypersecretion, greater glucose transporter 2 (GLUT2) expression, increased glycolytic flux and reduced mitochondrial complex III activity. Swimming training attenuated islet hypertrophy and normalised GLUT2 expression, contributing to a reduction in the glucose responsiveness of pancreatic islets from MSG-treated rats without altering glycolytic flux. However, physical training increased the activity of mitochondrial complex III in pancreatic islets from MSG-treated rats without a subsequent increase in glucose-induced insulin secretion. Copyright © 2013 S. Karger AG, Basel.

Glucose Deprivation Triggers Protein Kinase C-dependent β-Catenin Proteasomal Degradation*

PubMed Central

Choi, Seung-Won; Song, Jun-Kyu; Yim, Ye-Seal; Yun, Ho-Geun; Chun, Kyung-Hee

2015-01-01

Autophagy is a conserved process that contributes to cell homeostasis. It is well known that induction mainly occurs in response to nutrient starvation, such as starvation of amino acids and insulin, and its mechanisms have been extensively characterized. However, the mechanisms behind cellular glucose deprivation-induced autophagy are as of now poorly understood. In the present study, we determined a mechanism by which glucose deprivation induced the PKC-dependent proteasomal degradation of β-catenin, leading to autophagy. Glucose deprivation was shown to cause a sub-G1 transition and enhancement of the LC3-II protein levels, whereas β-catenin protein underwent degradation in a proteasome-dependent manner. Moreover, the inhibition of GSK3β was unable to abolish the glucose deprivation-mediated β-catenin degradation or up-regulation of LC3-II protein levels, which suggested GSK3β-independent protein degradation. Intriguingly, the inhibition of PKCα using a pharmacological inhibitor and transfection of siRNA for PKCα was observed to effectively block glucose deprivation-induced β-catenin degradation as well as the increase in LC3-II levels and the accumulation of a sub-G1 population. Together, our results demonstrated a molecular mechanism by which glucose deprivation can induce the GSK3β-independent protein degradation of β-catenin, leading to autophagy. PMID:25691573

AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells.

PubMed

Yamada, Shigeru; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

2013-05-01

Organotin compounds such as tributyltin (TBT) are known to cause various forms of cytotoxicity, including developmental toxicity and neurotoxicity. However, the molecular target of the toxicity induced by nanomolar levels of TBT has not been identified. In the present study, we found that exposure to 100 nM TBT induced growth arrest in human pluripotent embryonic carcinoma cell line NT2/D1. Since glucose provides metabolic energy, we focused on the glycolytic system. We found that exposure to TBT reduced the levels of both glucose-6-phosphate and fructose-6-phosphate. To investigate the effect of TBT exposure on glycolysis, we examined glucose transporter (GLUT) activity. TBT exposure inhibited glucose uptake via a decrease in the level of cell surface-bound GLUT1. Furthermore, we examined the effect of AMP-activated protein kinase (AMPK), which is known to regulate glucose transport by facilitating GLUT translocation. Treatment with the potent AMPK activator, AICAR, restored the TBT-induced reduction in cell surface-bound GLUT1 and glucose uptake. In conclusion, these results suggest that exposure to nanomolar levels of TBT causes growth arrest by targeting glycolytic systems in human embryonic carcinoma cells. Thus, understanding the energy metabolism may provide new insights into the mechanisms of metal-induced cytotoxicity.

Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

PubMed

Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

2015-08-01

Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Dual effect of cell-cell contact disruption on cytosolic calcium and insulin secretion.

PubMed

Jaques, Fabienne; Jousset, Hélène; Tomas, Alejandra; Prost, Anne-Lise; Wollheim, Claes B; Irminger, Jean-Claude; Demaurex, Nicolas; Halban, Philippe A

2008-05-01

Cell-to-cell interactions play an important role in insulin secretion. Compared with intact islets, dispersed pancreatic beta-cells show increased basal and decreased glucose-stimulated insulin secretion. In this study, we used mouse MIN6B1 cells to investigate the mechanisms that control insulin secretion when cells are in contact with each other or not. RNAi-mediated silencing of the adhesion molecule E-cadherin in confluent cells reduced glucose-stimulated secretion to the levels observed in isolated cells but had no impact on basal secretion. Dispersed cells presented high cytosolic Ca(2+) activity, depolymerized cytoskeleton and ERK1/2 activation in low glucose conditions. Both the increased basal secretion and the spontaneous Ca(2+) activity were corrected by transient removal of Ca(2+) or prolonged incubation of cells in low glucose, a procedure that restored the ability of dispersed cells to respond to glucose (11-fold stimulation). In conclusion, we show that dispersed pancreatic beta-cells can respond robustly to glucose once their elevated basal secretion has been corrected. The increased basal insulin secretion of dispersed cells is due to spontaneous Ca(2+) transients that activate downstream Ca(2+) effectors, whereas engagement of cell adhesion molecules including E-cadherin contributes to the greater secretory response to glucose seen in cells with normal intercellular contacts.

The Effects of Carbohydrates, in Isolation and Combined with Caffeine, on Cognitive Performance and Mood—Current Evidence and Future Directions

PubMed Central

Lawton, Clare Louise

2018-01-01

This review examines the effects of carbohydrates, delivered individually and in combination with caffeine, on a range of cognitive domains and subjective mood. There is evidence for beneficial effects of glucose at a dose of 25 g on episodic memory, but exploration of dose effects has not been systematic and the effects on other cognitive domains is not known. Factors contributing to the differential sensitivity to glucose facilitation include age, task difficulty/demand, task domain, and glucoregulatory control. There is modest evidence to suggest modulating glycemic response may impact cognitive function. The evidence presented in this review identifies dose ranges of glucose and caffeine which improve cognition, but fails to find convincing consistent synergistic effects of combining caffeine and glucose. Whilst combining glucose and caffeine has been shown to facilitate cognitive performance and mood compared to placebo or glucose alone, the relative contribution of caffeine and glucose to the observed effects is difficult to ascertain, due to the paucity of studies that have appropriately compared the effects of these ingredients combined and in isolation. This review identifies a number of methodological challenges which need to be considered in the design of future hypothesis driven research in this area. PMID:29425182

Estimating Plasma Glucose from Interstitial Glucose: The Issue of Calibration Algorithms in Commercial Continuous Glucose Monitoring Devices

PubMed Central

Rossetti, Paolo; Bondia, Jorge; Vehí, Josep; Fanelli, Carmine G.

2010-01-01

Evaluation of metabolic control of diabetic people has been classically performed measuring glucose concentrations in blood samples. Due to the potential improvement it offers in diabetes care, continuous glucose monitoring (CGM) in the subcutaneous tissue is gaining popularity among both patients and physicians. However, devices for CGM measure glucose concentration in compartments other than blood, usually the interstitial space. This means that CGM need calibration against blood glucose values, and the accuracy of the estimation of blood glucose will also depend on the calibration algorithm. The complexity of the relationship between glucose dynamics in blood and the interstitial space, contrasts with the simplistic approach of calibration algorithms currently implemented in commercial CGM devices, translating in suboptimal accuracy. The present review will analyze the issue of calibration algorithms for CGM, focusing exclusively on the commercially available glucose sensors. PMID:22163505

Ondansetron attenuates depression co-morbid with obesity in obese mice subjected to chronic unpredictable mild stress; an approach using behavioral battery tests.

PubMed

Kurhe, Yeshwant; Radhakrishnan, Mahesh; Gupta, Deepali

2014-09-01

The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedures for 4 weeks. Treatment with ondansetron was started on day 15. After day 28 behavioral assays and biochemical estimations were performed. Behavioral paradigms viz. sucrose preference test, locomotor score, forced swim test (FST) and elevated plus maze (EPM), whereas biochemical parameters like plasma glucose, total cholesterol, triglycerides and total proteins were estimated. Results examines that in behavioral assays, ondansetron significantly (P < 0.05) increased sucrose consumption, reduced immobility time in FST, increased the percent entries and time in open arm in EPM. In biochemical assessments elevated plasma glucose, total cholesterol, triglycerides and total proteins were significantly (P < 0.05) reversed by ondansetron treatment in HFD obese animals subjected to CUMS. The study indicates that the obese mice subjected to CUMS exhibited severe depressive-like symptoms and ondansetron significantly reversed the behavioral and biochemical alterations. In the present study the plasma glucose level indicates that, it could be "altered glucose level" playing an important role in depression co-morbid with obesity. Ondansetron through allosteric modulation of serotonergic system elevates the serotonin level and thereby regulates the insulin secretion and hence, reversing the "altered glucose level", could be the possible antidepressive-like mechanism against depression co-morbid with obesity.

The Accuracy Benefit of Multiple Amperometric Glucose Sensors in People With Type 1 Diabetes

PubMed Central

Castle, Jessica R.; Pitts, Amy; Hanavan, Kathryn; Muhly, Rhonda; El Youssef, Joseph; Hughes-Karvetski, Colleen; Kovatchev, Boris; Ward, W. Kenneth

2012-01-01

OBJECTIVE To improve glucose sensor accuracy in subjects with type 1 diabetes by using multiple sensors and to assess whether the benefit of redundancy is affected by intersensor distance. RESEARCH DESIGN AND METHODS Nineteen adults with type 1 diabetes wore four Dexcom SEVEN PLUS subcutaneous glucose sensors during two 9-h studies. One pair of sensors was worn on each side of the abdomen, with each sensor pair placed at a predetermined distance apart and 20 cm away from the opposite pair. Arterialized venous blood glucose levels were measured every 15 min, and sensor glucose values were recorded every 5 min. Sensors were calibrated once at the beginning of the study. RESULTS The use of four sensors significantly reduced very large errors compared with one sensor (0.4 vs. 2.6% of errors ≥50% from reference glucose, P < 0.001) and also improved overall accuracy (mean absolute relative difference, 11.6 vs. 14.8%, P < 0.001). Using only two sensors also significantly improved very large errors and accuracy. Intersensor distance did not affect the function of sensor pairs. CONCLUSIONS Sensor accuracy is significantly improved with the use of multiple sensors compared with the use of a single sensor. The benefit of redundancy is present even when sensors are positioned very closely together (7 mm). These findings are relevant to the design of an artificial pancreas device. PMID:22357189

The accuracy benefit of multiple amperometric glucose sensors in people with type 1 diabetes.

PubMed

Castle, Jessica R; Pitts, Amy; Hanavan, Kathryn; Muhly, Rhonda; El Youssef, Joseph; Hughes-Karvetski, Colleen; Kovatchev, Boris; Ward, W Kenneth

2012-04-01

To improve glucose sensor accuracy in subjects with type 1 diabetes by using multiple sensors and to assess whether the benefit of redundancy is affected by intersensor distance. Nineteen adults with type 1 diabetes wore four Dexcom SEVEN PLUS subcutaneous glucose sensors during two 9-h studies. One pair of sensors was worn on each side of the abdomen, with each sensor pair placed at a predetermined distance apart and 20 cm away from the opposite pair. Arterialized venous blood glucose levels were measured every 15 min, and sensor glucose values were recorded every 5 min. Sensors were calibrated once at the beginning of the study. The use of four sensors significantly reduced very large errors compared with one sensor (0.4 vs. 2.6% of errors ≥50% from reference glucose, P < 0.001) and also improved overall accuracy (mean absolute relative difference, 11.6 vs. 14.8%, P < 0.001). Using only two sensors also significantly improved very large errors and accuracy. Intersensor distance did not affect the function of sensor pairs. Sensor accuracy is significantly improved with the use of multiple sensors compared with the use of a single sensor. The benefit of redundancy is present even when sensors are positioned very closely together (7 mm). These findings are relevant to the design of an artificial pancreas device.

A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway.

PubMed

Lo, Hsin-Yi; Ho, Tin-Yun; Li, Chia-Cheng; Chen, Jaw-Chyun; Liu, Jau-Jin; Hsiang, Chien-Yun

2014-09-10

Diabetes, a common metabolic disorder, is characterized by hyperglycemia. Insulin is the principal mediator of glucose homeostasis. In a previous study, we identified a trypsin inhibitor, named Momordica charantia insulin receptor (IR)-binding protein (mcIRBP) in this study, that might interact with IR. The physical and functional interactions between mcIRBP and IR were clearly analyzed in the present study. Photo-cross-linking coupled with mass spectrometry showed that three regions (17-21, 34-40, and 59-66 residues) located on mcIRBP physically interacted with leucine-rich repeat domain and cysteine-rich region of IR. IR-binding assay showed that the binding behavior of mcIRBP and insulin displayed a cooperative manner. After binding to IR, mcIRBP activated the kinase activity of IR by (5.87 ± 0.45)-fold, increased the amount of phospho-IR protein by (1.31 ± 0.03)-fold, affected phosphoinositide-3-kinase/Akt pathways, and consequently stimulated the uptake of glucose in 3T3-L1 cells by (1.36 ± 0.12)-fold. Intraperitoneal injection of 2.5 nmol/kg mcIRBP significantly decreased the blood glucose levels by 20.9 ± 3.2% and 10.8 ± 3.6% in normal and diabetic mice, respectively. Microarray analysis showed that mcIRBP affected genes involved in insulin signaling transduction pathway in mice. In conclusion, our findings suggest that mcIRBP is a novel IRBP that binds to sites different from the insulin-binding sites on IR and stimulates both the glucose uptake in cells and the glucose clearance in mice.

Glucose meters: evaluation of the new formulation measuring strips from Roche (Accu-Chek) and Abbott (MediSense).

PubMed

Dimeski, G; Jones, B W; Tilley, V; Greenslade, M N; Russell, A W

2010-07-01

Both Roche and Abbott have released new glucose meter strips. They supply the entire Australian hospital market. The present study compared the performance of the new strips utilizing various specimen types (capillary, venous lithium heparin whole blood, venous lithium heparin plasma and serum) and evaluated how well they comply with the International Standards Organization (ISO) 15197 criteria. The study included imprecision, patient comparison and interference studies. Participants with and without diabetes were recruited to evaluate the performance of various specimen types against the Beckman DxC800 glucose method. The strips were tested for different interferences: galactose, maltose, lactose, Icodextrin, Intragam, paracetamol, sodium, ascorbic acid, variable strip storage temperature, haematocrit, haemolysis and lipaemia. The imprecision of the two strips was approximately 5% or less, except for the Abbott strip at very low values (1.4 mmol/L), approximately 7%. In total, 78% and 84%, respectively, of the results from the finger prick capillary specimens with the Roche (Accu-Chek Performa meter) and Abbott (Optium Xceed meter) strips, not 95% or greater as recommended by the ISO guideline, were within the recommended limits compared with reference plasma estimation on laboratory analysers. Galactose, ascorbic acid, haematocrit and sodium on the Roche and ascorbic acid and haematocrit on the Abbott strip continue to interfere to a variable degree with the glucose measurement. Analytically small differences exist between the glucose meter strips. The most significant analytical difference with the strips was at low glucose levels when compared with laboratory analyses and this may be of clinical importance. The impact of some of the interferences is variable between the two strips. Individuals, health-care professionals and health-care institutions should consider these data when selecting glucose meters for the management of people with diabetes mellitus.

Identification of glucose-fermenting bacteria in a full-scale enhanced biological phosphorus removal plant by stable isotope probing.

PubMed

Nielsen, Jeppe Lund; Nguyen, Hien; Meyer, Rikke Louise; Nielsen, Per Halkjær

2012-07-01

Microbiology in wastewater treatment has mainly been focused on problem-causing filamentous bacteria or bacteria directly involved in nitrogen and phosphorus removal, and to a lesser degree on flanking groups, such as hydrolysing and fermenting bacteria. However, these groups constitute important suppliers of readily degradable substrates for the overall processes in the plant. This study aimed to identify glucose-fermenting bacteria in a full-scale enhanced biological phosphorus removal (EBPR) wastewater treatment plant (WWTP), and to determine their abundance in similar WWTPs. Glucose-fermenting micro-organisms were identified by an in situ approach using RNA-based stable isotope probing. Activated sludge was incubated anaerobically with (13)C(6)-labelled glucose, and (13)C-enriched rRNA was subsequently reverse-transcribed and used to construct a 16S rRNA gene clone library. Phylogenetic analysis of the library revealed the presence of two major phylogenetic groups of gram-positive bacteria affiliating with the genera Tetrasphaera, Propionicimonas (Actinobacteria), and Lactococcus and Streptococcus (Firmicutes). Specific oligonucleotide probes were designed for fluorescence in situ hybridization (FISH) to specifically target the glucose-fermenting bacteria identified in this study. The combination of FISH with microautoradiography confirmed that Tetrasphaera, Propionicimonas and Streptococcus were the dominant glucose fermenters. The probe-defined fermenters were quantified in 10 full-scale EBPR plants and averaged 39 % of the total biovolume. Tetrasphaera and Propionicimonas were the most abundant glucose fermenters (average 33 and 4 %, respectively), while Streptococcus and Lactococcus were present only in some WWTPs (average 1 and 0.4 %, respectively). Thus the population of actively metabolizing glucose fermenters seems to occupy a relatively large component of the total biovolume.

Decreased complexity of glucose dynamics in diabetes: evidence from multiscale entropy analysis of continuous glucose monitoring system data.

PubMed

Chen, Jin-Long; Chen, Pin-Fan; Wang, Hung-Ming

2014-07-15

Parameters of glucose dynamics recorded by the continuous glucose monitoring system (CGMS) could help in the control of glycemic fluctuations, which is important in diabetes management. Multiscale entropy (MSE) analysis has recently been developed to measure the complexity of physical and physiological time sequences. A reduced MSE complexity index indicates the increased repetition patterns of the time sequence, and, thus, a decreased complexity in this system. No study has investigated the MSE analysis of glucose dynamics in diabetes. This study was designed to compare the complexity of glucose dynamics between the diabetic patients (n = 17) and the control subjects (n = 13), who were matched for sex, age, and body mass index via MSE analysis using the CGMS data. Compared with the control subjects, the diabetic patients revealed a significant increase (P < 0.001) in the mean (diabetic patients 166.0 ± 10.4 vs. control subjects 93.3 ± 1.5 mg/dl), the standard deviation (51.7 ± 4.3 vs. 11.1 ± 0.5 mg/dl), and the mean amplitude of glycemic excursions (127.0 ± 9.2 vs. 27.7 ± 1.3 mg/dl) of the glucose levels; and a significant decrease (P < 0.001) in the MSE complexity index (5.09 ± 0.23 vs. 7.38 ± 0.28). In conclusion, the complexity of glucose dynamics is decreased in diabetes. This finding implies the reactivity of glucoregulation is impaired in the diabetic patients. Such impairment presenting as an increased regularity of glycemic fluctuating pattern could be detected by MSE analysis. Thus, the MSE complexity index could potentially be used as a biomarker in the monitoring of diabetes.

Real-time continuous glucose monitoring versus conventional glucose monitoring in critically ill patients: a systematic review study protocol.

PubMed

Zhu, Weidong; Jiang, Libing; Jiang, Shouyin; Ma, Yuefeng; Zhang, Mao

2015-01-23

Stress-induced hyperglycaemia, which has been shown to be associated with an unfavourable prognosis, is common among critically ill patients. Additionally, it has been reported that hypoglycaemia and high glucose variabilities are also associated with adverse outcomes. Thus, continuous glucose monitoring (CGM) may be the optimal method to detect severe hypoglycaemia, hyperglycaemia and decrease glucose excursion. However, the overall accuracy and reliability of CGM systems and the effects of CGM systems on glucose control and prognosis in critically ill patients remain inconclusive. Therefore, we will conduct a systematic review and meta-analysis to clarify the associations between CGM systems and clinical outcome. We will search PubMed, EMBASE and the Cochrane Library from inception to October 2014. Studies comparing CGM systems with any other glucose monitoring methods in critically ill patients will be eligible for our meta-analysis. The primary endpoints include the incidence of hypoglycaemia and hyperglycaemia, mean glucose level, and percentage of time within the target range. The second endpoints include intensive care unit (ICU) mortality, hospital mortality, duration of mechanical ventilation, length of ICU and hospital stay, and the Pearson correlation coefficient and the results of error grid analysis. In addition, we will record all complications (eg, acquired infections) in control and intervention groups and local adverse events in intervention groups (eg, bleeding or infections). Ethics approval is not required as this is a protocol for a systematic review. The findings will be disseminated in a peer-reviewed journal and presented at a relevant conference. PROSPERO registration number: CRD42014013488. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of a point-of-care electrochemical meter to detect subclinical ketosis and hypoglycaemia in lactating dairy cows.

PubMed

Zakian, A; Tehrani-Sharif, M; Mokhber-Dezfouli, M R; Nouri, M; Constable, P D

2017-04-01

To evaluate and validate a hand-held electrochemical meter (Precision Xtra®) as a screening test for subclinical ketosis and hypoglycaemia in lactating dairy cattle. Method comparison study using a convenience sample. Blood samples were collected into plain tubes from the coccygeal vessels of 181 Holstein cows at 2-4 weeks of lactation during summer in Iran. Blood β-hydroxybutyrate concentration (BHB) and glucose concentration were immediately measured by the electrochemical meter after applying 20 μL of blood to the reagent strip. Passing-Bablok regression and Bland-Altman plots were used to determine the accuracy of the meter against laboratory reference methods (BHB dehydrogenase and glucose oxidase). Serum BHB ranged from 0.1 to 7.3 mmol/L and serum glucose ranged from 0.9 to 5.1 mmol/L. Passing-Bablok regression analysis indicated that the electrochemical meter and reference methods were linearly related for BHB and glucose, with a slope estimate that was not significantly different from 1.00. Clinically minor, but statistically significant, differences were present for the intercept value for Passing-Bablok regression analysis for BHB and glucose, and bias estimates in the Bland-Altman plots for BHB and glucose. The electrochemical meter provided a clinically useful method to detect subclinical ketosis and hypoglycaemia in lactating dairy cows. Compared with other method validation studies using the meter, we attributed the improved performance of the electrochemical meter to application of a fixed volume of blood (20 μL) to the reagent strip, use of the meter in hot ambient conditions and use of glucose oxidase as the reference method for glucose analysis. © 2017 Australian Veterinary Association.

Pancreas-Specific Sirt1-Deficiency in Mice Compromises Beta-Cell Function without Development of Hyperglycemia.

PubMed

Pinho, Andreia V; Bensellam, Mohammed; Wauters, Elke; Rees, Maxine; Giry-Laterriere, Marc; Mawson, Amanda; Ly, Le Quan; Biankin, Andrew V; Wu, Jianmin; Laybutt, D Ross; Rooman, Ilse

2015-01-01

Sirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear. This study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1Cre; Sirt1ex4F/F mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas. We found that in the Pdx1Cre; Sirt1ex4F/F mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2a2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas. This study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncovered a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted.

Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis.

PubMed

Ito, Satoshi; Nagoshi, Tomohisa; Minai, Kosuke; Kashiwagi, Yusuke; Sekiyama, Hiroshi; Yoshii, Akira; Kimura, Haruka; Inoue, Yasunori; Ogawa, Kazuo; Tanaka, Toshikazu D; Ogawa, Takayuki; Kawai, Makoto; Yoshimura, Michihiro

2017-01-01

Although glucose-insulin-potassium (GIK) therapy ought to be beneficial for ischemic heart disease in general, variable outcomes in many clinical trials of GIK in acute coronary syndrome (ACS) had a controversial impact. This study was designed to examine whether "insulin resistance" is involved in ACS and to clarify other potential intrinsic compensatory mechanisms for GIK tolerance through highly statistical procedure. We compared the degree of insulin resistance during ACS attack and remission phase after treatment in individual patients (n = 104). During ACS, homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly increased (P<0.001), while serum potassium levels were transiently decreased (degree of which was indicated by ΔK) (P<0.001). This finding provides a renewed paradox, as ΔK, a surrogate marker of intrinsic GIK cascade activation, probably reflects the validated glucose metabolism during ischemic attack. Indeed, multiple regression analysis revealed that plasma glucose level during ACS was positively correlated with ΔK (P = 0.026), whereas HOMA-IR had no impact on ΔK. This positive correlation between ΔK and glucose was confirmed by covariance structure analysis with a strong impact (β: 0.398, P = 0.015). Intriguingly, a higher incidence of myocardial infarction relative to unstable angina pectoris, as well as a longer hospitalization period were observed in patients with larger ΔK, indicating that ΔK also reflects disease severity of ACS. Insulin resistance most likely increases during ACS; however, ΔK was positively correlated with plasma glucose level, which overwhelmed insulin resistance condition. The present study with covariance structure analysis suggests that there are potential endogenous glucose-coupled potassium lowering mechanisms, other than insulin, regulating glucose metabolism during ACS.

Circulating irisin and glucose metabolism in overweight/obese women: effects of α-lipoic acid and eicosapentaenoic acid.

PubMed

Huerta, A E; Prieto-Hontoria, P L; Fernández-Galilea, M; Sáinz, N; Cuervo, M; Martínez, J A; Moreno-Aliaga, M J

2015-09-01

Irisin is a myokine/adipokine with potential role in obesity and diabetes. The objectives of the present study were to analyse the relationship between irisin and glucose metabolism at baseline and during an oral glucose tolerance test (OGTT) and to determine the effects of eicosapentaenoic acid (EPA) and/or α-lipoic acid treatment on irisin production in cultured human adipocytes and in vivo in healthy overweight/obese women following a weight loss program. Seventy-three overweight/obese women followed a 30% energy-restricted diet supplemented without (control) or with EPA (1.3 g/day), α-lipoic acid (0.3 g/day) or both EPA + α-lipoic acid (1.3 + 0.3 g/day) during 10 weeks. An OGTT was performed at baseline. Moreover, human adipocytes were treated with EPA (100-200 μM) or α-lipoic acid (100-250 μM) during 24 h. At baseline plasma, irisin circulating levels were positively associated with glucose levels; however, serum irisin concentrations were not affected by the increment in blood glucose or insulin during the OGTT. Treatment with α-lipoic acid (250 μM) upregulated Fndc5 messenger RNA (mRNA) and irisin secretion in cultured adipocytes. In overweight/obese women, irisin circulating levels decreased significantly after weight loss in all groups, while no additional differences were induced by EPA or α-lipoic acid supplementation. Moreover, plasma irisin levels were positively associated with higher glucose concentrations at beginning and at endpoint of the study. The data from the OGTT suggest that glucose is not a direct contributing factor of irisin release. The higher irisin levels observed in overweight/obese conditions could be a protective response of organism to early glucose impairments.

Near-infrared imaging of the effects of glucose ingestion and regulation on prefrontal activation during dual-task execution in healthy fasting older adults.

PubMed

Gagnon, Christine; Desjardins-Crépeau, Laurence; Tournier, Isabelle; Desjardins, Michèle; Lesage, Frédéric; Greenwood, Carol E; Bherer, Louis

2012-06-15

Glucose enhancing effects in older adults have mostly been observed for episodic memory, but have recently been found for attentional control performance. Yet, brain activation patterns underlying these effects are still unknown. The present study examined the acute effects of glucose ingestion on prefrontal brain activation during the execution of a divided attention task in fasting non-diabetic older adults. Twenty older adults (60 years and older) took part in the study that included two experimental sessions. After an overnight fast, participants received either a glucose drink (50 g) or a placebo (saccharin) drink, following which they completed a dual-task. During task execution, prefrontal activation was recorded with functional near-infrared spectroscopy (fNIRS). A repeated-measures design was used such that each participant served as his or her own control. The two experimental sessions were counterbalanced among participants and were performed two weeks apart. When participants were in the glucose condition, they showed similar dual-task costs for both tasks, whereas in the placebo condition they prioritized one task over the other, with a significantly larger dual-task cost for the non-prioritized task (p<0.01). Differential brain activation was also observed in right ventral-lateral prefrontal regions for oxygenated hemoglobin and deoxygenated hemoglobin, with more activation apparent in the glucose condition (p<0.05). Furthermore, behavioral and activation data were influenced by individual differences in glucose regulation. Glucose ingestion appears to momentarily enhance fasting seniors' capacity to coordinate more equally two concurrent tasks and this is reflected in brain activation patterns. Copyright © 2012 Elsevier B.V. All rights reserved.

Accuracy of a continuous glucose monitoring system in dogs and cats with diabetic ketoacidosis.

PubMed

Reineke, Erica L; Fletcher, Daniel J; King, Lesley G; Drobatz, Kenneth J

2010-06-01

(1) To determine the ability of a continuous interstitial glucose monitoring system (CGMS) to accurately estimate blood glucose (BG) in dogs and cats with diabetic ketoacidosis. (2) To determine the effect of perfusion, hydration, body condition score, severity of ketosis, and frequency of calibration on the accuracy of the CGMS. Prospective study. University Teaching Hospital. Thirteen dogs and 11 cats diagnosed with diabetic ketoacidosis were enrolled in the study within 24 hours of presentation. Once BG dropped below 22.2 mmol/L (400 mg/dL), a sterile flexible glucose sensor was placed aseptically in the interstitial space and attached to the continuous glucose monitoring device for estimation of the interstitial glucose every 5 minutes. BG measurements were taken with a portable BG meter every 2-4 hours at the discretion of the primary clinician and compared with CGMS glucose measurements. The CGMS estimates of BG and BG measured on the glucometer were strongly associated regardless of calibration frequency (calibration every 8 h: r=0.86, P<0.001; calibration every 12 h: r=0.85, P<0.001). Evaluation of this data using both the Clarke and Consensus error grids showed that 96.7% and 99% of the CGMS readings, respectively, were deemed clinically acceptable (Zones A and B errors). Interpatient variability in the accuracy of the CGMS glucose measurements was found but was not associated with body condition, perfusion, or degree of ketosis. A weak association between hydration status of the patient as assessed with the visual analog scale and absolute percent error (Spearman's rank correlation, rho=-0.079, 95% CI=-0.15 to -0.01, P=0.03) was found, with the device being more accurate in the more hydrated patients. The CGMS provides clinically accurate estimates of BG in patients with diabetic ketoacidosis.

The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

PubMed Central

Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

2012-01-01

The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain. PMID:23202918

Postpartum outcomes in women with gestational diabetes and their offspring: POGO study design and first-year results.

PubMed

Hummel, Sandra; Much, Daniela; Rossbauer, Michaela; Ziegler, Anette-G; Beyerlein, Andreas

2013-01-01

Gestational diabetes mellitus (GDM) is a risk factor for mothers to develop type 2 diabetes (T2D) postpartum, and for their children to develop obesity. The aim of the ongoing POGO study is to identify long-lasting changes in the maternal and fetal metabolism and microbiome, after GDM, which contribute to subsequent development of T2D and obesity. Women screened for GDM are asked to attend a postpartum study visit together with their offspring. At the visit, demographic, nutritional, and anthropometric data are recorded. Additionally, data about physical activity, metabolism, and genetic susceptibility are collected using accelerometers, breath gas analyses, 75g oral glucose tolerance tests (OGTT), and bio-samples such as blood and stool. To date, 121 women (median follow-up time postpartum: 5.5 years) have been enrolled together with 133 index children. GDM has been diagnosed using OGTT in 105 women (and 117 children). It showed that 47 mothers had abnormal glucose tolerance, including 19 cases of impaired glucose tolerance, 19 of impaired fasting glucose, eight with T2D, and one with type 1 diabetes (T1D). The prevalence of obesity in the offspring of GDM mothers was 5.1%. Of 61 children tested by OGTT, three were diagnosed with impaired glucose tolerance, another three with impaired fasting glucose, and none with T1D or T2D. The POGO study will contribute to the understanding of the pathogenesis of T2D and obesity after GDM, and will thus help to develop appropriate prevention and intervention strategies. This article presents the first results of the ongoing study, which are looking promising.

Elucidation of the glucose transport pathway in glucose transporter 4 via steered molecular dynamics simulations.

PubMed

Sheena, Aswathy; Mohan, Suma S; Haridas, Nidhina Pachakkil A; Anilkumar, Gopalakrishnapillai

2011-01-01

GLUT4 is a predominant insulin regulated glucose transporter expressed in major glucose disposal tissues such as adipocytes and muscles. Under the unstimulated state, GLUT4 resides within intracellular vesicles. Various stimuli such as insulin translocate this protein to the plasma membrane for glucose transport. In the absence of a crystal structure for GLUT4, very little is known about the mechanism of glucose transport by this protein. Earlier we proposed a homology model for GLUT4 and performed a conventional molecular dynamics study revealing the conformational rearrangements during glucose and ATP binding. However, this study could not explain the transport of glucose through the permeation tunnel. To elucidate the molecular mechanism of glucose transport and its energetic, a steered molecular dynamics study (SMD) was used. Glucose was pulled from the extracellular end of GLUT4 to the cytoplasm along the pathway using constant velocity pulling method. We identified several key residues within the tunnel that interact directly with either the backbone ring or the hydroxyl groups of glucose. A rotation of glucose molecule was seen near the sugar binding site facilitating the sugar recognition process at the QLS binding site. This study proposes a possible glucose transport pathway and aids the identification of several residues that make direct interactions with glucose during glucose transport. Mutational studies are required to further validate the observation made in this study.

Relationship between hyperglycemia, hormone disturbances, and clinical evolution in severely hyperglycemic post surgery critically ill children: an observational study

PubMed Central

2014-01-01

Background To study hormonal changes associated with severe hyperglycemia in critically ill children and the relationship with prognosis and length of stay in intensive care. Methods Observational study in twenty-nine critically ill children with severe hyperglycemia defined as 2 blood glucose measurements greater than 180 mg/dL. Severity of illness was assessed using pediatric index of mortality (PIM2), pediatric risk of mortality (PRISM) score, and pediatric logistic organ dysfunction (PELOD) scales. Blood glucose, glycosuria, insulin, C-peptide, cortisol, corticotropin, insulinlike growth factor-1, growth hormone, thyrotropin, thyroxine, and treatment with insulin were recorded. β-cell function and insulin sensitivity and resistance were determined on the basis of the homeostatic model assessment (HOMA), using blood glucose and C-peptide levels. Results The initial blood glucose level was 249 mg/dL and fell gradually to 125 mg/dL at 72 hours. Initial β-cell function (49.2%) and insulin sensitivity (13.2%) were low. At the time of diagnosis of hyperglycemia, 50% of the patients presented insulin resistance and β-cell dysfunction, 46% presented isolated insulin resistance, and 4% isolated β-cell dysfunction. β-cell function improved rapidly but insulin resistance persisted. Initial glycemia did not correlate with any other factor, and there was no relationship between glycemia and mortality. Patients who died had higher cortisol and growth hormone levels at diagnosis. Length of stay was correlated by univariate analysis, but not by multivariate analysis, with C-peptide and glycemic control at 24 hours, insulin resistance, and severity of illness scores. Conclusions Critically ill children with severe hyperglycemia initially present decreased β-cell function and insulin sensitivity. Nonsurvivors had higher cortisol and growth hormone levels and developed hyperglycemia later than survivors. PMID:24628829

Drug-induced cerebral glucose metabolism resembling Alzheimer's Disease: a case study.

PubMed

Riepe, Matthias W; Walther, Britta; Vonend, Catharina; Beer, Ambros J

2015-07-11

With aging of society the absolute number and the proportion of patients with cognitive deficits increase. Multiple disorders and diseases can foster cognitive impairment, e.g., Alzheimer's disease (AD), depressive disorder, or polypharmacy. A 74 year old man presented to the Old Age Psychiatry Service with cognitive deficits while being treated for recurrent depressive episodes and essential tremor with Venlafaxine, Lithium, and Primidone. Neuropsychological testing revealed a medio-temporal pattern of deficits with pronounced impairment of episodic memory, particularly delayed recall. Likewise, cognitive flexibility, semantic fluency, and attention were impaired. Positron emission tomography (PET) with fluorodeoxyglucose was performed and revealed a pattern of glucose utilization deficit resembling AD. On cessation of treatment with Lithium and Primidone, cognitive performance improved, particularly episodic memory performance and cognitive flexibility. Likewise, glucose metabolism normalized. Despite normalization of both, clinical symptoms and glucose utilization, the patient remained worried about possible underlying Alzheimer's disease pathology. To rule this out, an amyloid-PET was performed. No cortical amyloid was observed. Pharmacological treatment of older subjects may mimic glucose metabolism and clinical symptoms of Alzheimer's disease. In the present case both, imaging and clinical findings, reversed to normal on change of treatment. Amyloid PET is a helpful tool to additionally rule out underlying Alzheimer's disease in situations of clinical doubt even if clinical or other imaging findings are suggestive of Alzheimer's disease.

Beneficial effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice.

PubMed

Fang, Penghua; Yu, Mei; Min, Wen; Han, Shiyu; Shi, Mingyi; Zhang, Zhenwen; Bo, Ping

2018-05-01

Although baicalin has been shown to increase glucose uptake and insulin sensitivity in skeletal muscle of mice, there is no literature available about the effect of baicalin on insulin sensitivity in adipocytes of diet-induced obese mice. In the present study, diet-induced obese mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and 3T3-L1 cells were treated with 100, 200, 400 μM baicalin for 3 h. Then insulin resistance indexes and insulin signal protein levels were examined to elucidate whether baicalin increased glucose uptake and GLUT4 translocation in adipocytes of diet-induced obese mice. The present findings showed that administration of baicalin decreased food intake, body weight, HOMA-IR and p-p38 MAPK and pERK levels, but enhanced pAKT and PGC-1α contents, as well as GLUT4 mRNA, PGC-1α mRNA expression in adipocytes, and reversed high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Moreover, baicalin treatment increased GLUT4 concentration in plasma membranes of adipocytes. These data demonstrated that baicalin accelerated GLUT4 translocation from intracellular membrane compartments to plasma membranes in adipocytes. Baicalin plays a significant role in elevation of glucose uptake and insulin sensitivity to promote glucose clearance. Copyright © 2018 Elsevier B.V. All rights reserved.

Unsuccessful attempts to replicate effects of self control operations and glucose on ego-depletion pose an interesting research question that demands explanation.

PubMed

Chatzisarantis, Nikos L D; Hagger, Martin S

2015-01-01

The hypothesis that sugar-containing drinks counteract depletion of self-control or ego resources is elegant and provocative because it entails that the origins of ego-energy and self-control operations can be traced to a physiological substrate. However, this hypothesis has not withstood scientific scrutiny. Lange and Eggert presented two unsuccessful attempts to replicate effects of glucose on ego-depletion. Chatzisarantis and Hagger argued that inconsistent findings may be due to experimental designs that expose participants to similar acts of self-control. This methodology may not provide a rigorous test of the counteracting effects of glucose on ego-depletion because it does not control for factors (i.e., motivation) that interfere with glucose effects. In this article, we address Lange's comments and explore the possibility that findings reported by Lange and Eggert's and Hagger and Chatzisarantis' studies are consistent. In addition, we discuss a factor that researchers may wish to take into consideration when designing experiments that aim to test effects of glucose, or glucose rinsing, on ego-depletion. This factor is related to ego-depleting value of self-control tasks. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Glucose intolerance in a large cohort of mediterranean women with polycystic ovary syndrome: phenotype and associated factors.

PubMed

Gambineri, Alessandra; Pelusi, Carla; Manicardi, Elisa; Vicennati, Valentina; Cacciari, Mauro; Morselli-Labate, Antonio Maria; Pagotto, Uberto; Pasquali, Renato

2004-09-01

The aim of this study was to investigate the phenotypic parameters and associated factors characterizing the development of glucose intolerance in polycystic ovary syndrome (PCOS). Among the 121 PCOS female subjects from the Mediterranean region, 15.7 and 2.5% displayed impaired glucose tolerance and type 2 diabetes, respectively. These subjects were included in a single group of overweight or obese subjects presenting with glucose intolerance (GI) states. PCOS women with normal glucose tolerance (81.8%) were subdivided into two groups: those who were overweight or obese and those of normal weight. Metabolic and hormonal characteristics of the GI group included significantly higher fasting and glucose-stimulated insulin levels, more severe insulin resistance, hyperandrogenemia, and significantly higher cortisol and androstenedione responses to 1-24 ACTH stimulation. One important finding was that lower birth weight and earlier age of menarche were associated with GI in PCOS women. Frequency of hirsutism, oligomenorrhea, acne, and acanthosis nigricans did not characterize women with GI. Our findings indicate that PCOS patients with GI represent a subgroup with specific clinical and hormonal characteristics. Our observations may have an important impact in preventative and therapeutic strategies.

Decrease of hyperglycemia by syringaldehyde in diabetic rats.

PubMed

Kuo, S C; Chung, H H; Huang, C H; Cheng, J T

2014-01-01

Syringaldehyde is one of the active principles from the stems of Hibiscus taiwanensis (Malvaceae) that has been mentioned to lower hyperglycemia. However, the potential mechanisms for this action of syringaldehyde remain obscure. In the present study, we used streptozotocin to induce diabetic rats (STZ-diabetic rats) as type 1-like diabetic rats and fed fructose-rich chow to rats as type 2-like diabetic rats. Then, we performed the postprandial glucose test and applied the hyperinsulinemic euglycemic clamp to investigate the actions of syringaldehyde. Also, the changes of gene expressions of enzyme relating to glucose homeostasis in muscle and liver were characterized. Syringaldehyde significantly decreased the postprandial plasma glucose in rats, while the plasma insulin was not modified by syringaldehyde. The glucose infusion rate (GIR) in fructose chow-fed rats using hyperinsulinemic euglycemic clamp was markedly improved by syringaldehyde. Additionally, repeated administration of syringaldehyde for 3 days in STZ-diabetic rats resulted in a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Our results suggest that syringaldehyde may increase glucose utilization to lower hyperglycemia in diabetic rats. © Georg Thieme Verlag KG Stuttgart · New York.

In vitro studies on the hypoglycemic potential of Ficus racemosa stem bark.

PubMed

Ahmed, Faiyaz; Urooj, Asna

2010-02-01

Medicinal plants have been reported to play an important role in modulating glycemic responses and have preventive and therapeutic implications. Several mechanisms have been proposed for the antidiabetic effect of medicinal plants such as inhibition of carbohydrate-metabolizing enzymes, manipulation of glucose transporters, beta-cell regeneration and enhancing insulin-releasing activity. The present investigation evaluated the possible mechanism of action through which Ficus racemosa stem bark (Moraceae) exerts its hypoglycemic effect using suitable in vitro techniques. Ficus racemosa bark (FRB) exhibited significantly higher (P < or = 0.01) glucose-binding capacity than wheat bran (WB) and acarbose (ACB) consequently showed significantly higher (P < or = 0.01) retardation of glucose diffusion compared to WB and ACB. In case of amylolysis kinetics the liberation of glucose was greatly inhibited by FRB, as reflected by a significantly lower (P < or = 0.01) glucose diffusion rate in the system containing FRB compared to the control and acarbose. Furthermore, FRB significantly increased (P < or = 0.01) the rate of glucose transport across the yeast cell membrane and also in isolated rat hemi-diaphragm. The findings indicate F. racemosa bark to possess strong hypoglycemic effect and hence can be utilized as an adjunct in the management of diabetes mellitus.

Glucose & sodium chloride induced biofilm production & ica operon in clinical isolates of staphylococci.

PubMed

Agarwal, Astha; Jain, Amita

2013-01-01

All colonizing and invasive staphylococcal isolates may not produce biofilm but may turn biofilm producers in certain situations due to change in environmental factors. This study was done to test the hypothesis that non biofilm producing clinical staphylococci isolates turn biofilm producers in presence of sodium chloride (isotonic) and high concentration of glucose, irrespective of presence or absence of ica operon. Clinical isolates of 100 invasive, 50 colonizing and 50 commensal staphylococci were tested for biofilm production by microtiter plate method in different culture media (trypticase soy broth alone or supplemented with 0.9% NaCl/ 5 or 10% glucose). All isolates were tested for the presence of ica ADBC genes by PCR. Biofilm production significantly increased in the presence of glucose and saline, most, when both glucose and saline were used together. All the ica positive staphylococcal isolates and some ica negative isolates turned biofilm producer in at least one of the tested culture conditions. Those remained biofilm negative in different culture conditions were all ica negative. The present results showed that the use of glucose or NaCl or combination of both enhanced biofilm producing capacity of staphylococcal isolates irrespective of presence or absence of ica operon.

High glucose-induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells.

PubMed

Jiang, Zengxin; Lu, Wei; Zeng, Qingmin; Li, Defang; Ding, Lei; Wu, Jingping

2018-04-16

Diabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high-glucose medium (10% FBS + 0.1 M glucose or 10% FBS + 0.2 M glucose, experimental conditions) for 1 or 3 days. In addition, CEP cells were treated with 0.2 M glucose for 3 days in the presence or absence of alpha-lipoic acid (ALA, 0.15 M). Flow cytometry was performed to identify and quantify the degree of apoptosis. The expression of reactive oxygen species (ROS) was assessed by flow cytometry, and mitochondrial damage (mitochondrial membrane potential) was assessed by fluorescence microscopy. Furthermore, the expression levels of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, and cytochrome c were evaluated by Western blotting. High glucose significantly increased apoptosis and ROS accumulation in CEP cells in a dose- and time-dependent manner. Meanwhile, a disrupted mitochondrial membrane potential was detected in rat CEP cells cultured in the two high glucose concentrations. Incubating in high glucose enhanced the expression levels of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but decreased the level of the anti-apoptotic protein Bcl-2. ALA inhibited the expression of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but enhanced the expression of Bcl-2. ALA also prevented disruption of the mitochondrial membrane potential in CEP cells. This study demonstrates that high glucose-induced excessive reactive oxygen species promote mitochondrial damage, thus causing apoptosis in rat CEP cells in a dose- and time-dependent manner. ALA could prevent mitochondrial damage and apoptosis caused by high glucose in CEP cells. The results suggest that appropriate blood glucose control may be the key to preventing IDD in diabetic patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Evaluation of a new portable glucose meter designed for the use in cats.

PubMed

Zini, E; Moretti, S; Tschuor, F; Reusch, C E

2009-09-01

Portable blood glucose meters (PBGMs) are useful in the management of diabetes mellitus in cats. In the present study we compared the performance of two PBGMs: the AlphaTRAK (Abbott Animal Health, Maidenhead, England) specifically developed for dogs and cats, and the Ascensia ELITE (Bayer HealthCare, Zurich, Switzerland) developed for humans. Quality parameters, including precision and accuracy, were better for the AlphaTRAK meter compared to Ascensia ELITE. While the AlphaTRAK meter results did not differ from the reference method, results from the Ascensia ELITE were significantly (P<0.001) lower. The superior performance of the AlphaTRAK meter supports its use to monitor blood glucose levels in cats.

A BAT-Centric Approach to the Treatment of Diabetes: Turn on the Brain.

PubMed

Hankir, Mohammed K; Cowley, Michael A; Fenske, Wiebke K

2016-07-12

The marked (18)F-flurodeoxyglucose uptake by brown adipose tissue (BAT) enabled its identification in human positron emission tomography imaging studies. In this Perspective, we discuss how glucose extraction by BAT and beige adipose tissue (BeAT) sufficiently impacts on glycemic control. We then present a unique overview of the central circuits modulated by gluco-regulatory hormones, temperature, and glucose itself, which converge on sympathetic preganglionic neurons and whose activation syphon circulating glucose into BAT/BeAT. Targeted stimulation of the sympathetic nervous system at specific nodes to selectively recruit BAT/BeAT may represent a safe and effective means of treating diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Higher hdl levels are a preventive factor for metabolic syndrome in obese Turkish children.

PubMed

Özer, Samet; Yılmaz, Resul; Özlem Kazanci, Nafia; Sönmezgöz, Ergün; Karaaslan, Erhan; Altuntaş, Buket; Emre Kuyucu, Yunus

2014-10-03

The definition of childhood metabolic syndrome has not been described clearly. Childhood obesity is increasing gradually, and the incidence of childhood metabolic syndrome is also rising. We aimed to show metabolic syndrome components and preventive factors for metabolic syndrome in obese children Methods: In the present study, 187 obese children and adolescents 5-18 years old were investigated retrospectively. Demographic data, anthropometric measurements, body mass index, blood pressure values, insulin levels, oral glucose tolerance test results, total cholesterol, high density lipoprotein, and triglyceride levels were obtained from hospital records. A body mass index > 95th percentile was considered obese. Insulin resistance was calculated according to the oral glucose tolerance test with 1.75 g/kg glucose maximum 75 g glucose. The insulin sensitivity index and homeostatic model assessment-insulin resistance (HOMA IR) were calculated and compared. Metabolic syndrome was diagnosed according to the modified WHO criteria adapted for metabolic syndrome in children. Abnormal glucose homeostasis was detected in 53% of subjects. Dyslipidaemia was present in 45.7% and hypertension in 16.6% of the patients. Metabolic syndrome was identified in 24.6% of obese children and adolescents. High HOMA-IR values and fasting glucose levels, elevated triglycerides and lower HDL levels were an indication of metabolic syndrome. Obesity and insulin resistance are significant factors for the development of metabolic syndrome in children and adolescents. In obese children higher HDL levels are preventive factor for metabolic syndrome. Preventing obesity and insulin resistance may decrease the prevalence of metabolic syndrome. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Autophagy fails to prevent glucose deprivation/glucose reintroduction-induced neuronal death due to calpain-mediated lysosomal dysfunction in cortical neurons.

PubMed

Gerónimo-Olvera, Cristian; Montiel, Teresa; Rincon-Heredia, Ruth; Castro-Obregón, Susana; Massieu, Lourdes

2017-06-29

Autophagy is triggered during nutrient and energy deprivation in a variety of cells as a homeostatic response to metabolic stress. In the CNS, deficient autophagy has been implicated in neurodegenerative diseases and ischemic brain injury. However, its role in hypoglycemic damage is poorly understood and the dynamics of autophagy during the hypoglycemic and the glucose reperfusion periods, has not been fully described. In the present study, we analyzed the changes in the content of the autophagy proteins BECN1, LC3-II and p62/SQSTM1 by western blot, and autophagosome formation was followed through time-lapse experiments, during glucose deprivation (GD) and glucose reintroduction (GR) in cortical cultures. According to the results, autophagosome formation rapidly increased during GD, and was followed by an active autophagic flux early after glucose replenishment. However, cells progressively died during GR and autophagy inhibition reduced neuronal death. Neurons undergoing apoptosis during GR did not form autophagosomes, while those surviving up to late GR showed autophagosomes. Calpain activity strongly increased during GR and remained elevated during progressive neuronal death. Its activation led to the cleavage of LAMP2 resulting in lysosome membrane permeabilization (LMP) and release of cathepsin B to the cytosol. Calpain inhibition prevented LMP and increased the number of neurons containing lysosomes and autophagosomes increasing cell viability. Taken together, the present results suggest that calpain-mediated lysosome dysfunction during GR turns an adaptive autophagy response to energy stress into a defective autophagy pathway, which contributes to neuronal death. In these conditions, autophagy inhibition results in the improvement of cell survival.

Prenatal Food Restriction with Postweaning High-fat Diet Alters Glucose Metabolic Function in Adult Rat Offspring.

PubMed

Xiao, Di; Kou, Hao; Zhang, Li; Guo, Yu; Wang, Hui

2017-01-01

The present study was designed to investigate the effects of prenatal food restriction (PFR) with postweaning high-fat diet (HFD) on glucose metabolic function in adult offspring. Pregnant Wistar rats were given PFR treatment from gestational day 11 to spontaneous delivery. All pups were fed by HFD after weaning. Oral glucose tolerance test (OGTT) was conducted at postnatal week (PW) 20. Rats were decapitated in PW24 to collect liver and pancreas, and expression of hepatic insulin signaling genes were then quantified. Body weight from PW4 to PW24 in PFR males was lower than those in control males, whereas there was no distinct difference between females. However, body weight gain rates were higher from PW16 to PW24 in PFR males and females. Fasting serum glucose presented no changes, whereas fasting serum insulin decreased in PW20 in PFR pups. Moreover, glucose intolerance only appeared in PFR males, whereas no changes were shown in PFR females in relative values. Serum insulin increased in both PFR groups after OGTT. Remarkable pathological changes were also found in islets from PFR rats. There was an increase in the hepatic mRNA expression of IR in PFR females and of Glut2 in PFR males. PFR with postweaning HFD induced a catch-up growth in body weight, especially in PFR females. Serum insulin decreased in both PFR groups in fasting status. Insulin resistance after OGTT only existed in PFR males, whereas PFR females showed no obvious changes in glucose metabolism. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency.

PubMed

Akman, Cigdem Inan; Provenzano, Frank; Wang, Dong; Engelstad, Kristin; Hinton, Veronica; Yu, Julia; Tikofsky, Ronald; Ichese, Masonari; De Vivo, Darryl C

2015-02-01

(18)F fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) facilitates examination of glucose metabolism. Previously, we described regional cerebral glucose hypometabolism using (18)F FDG-PET in patients with Glucose transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in Glut1 DS using quantitative image analysis to identify the epileptic network based on the regional distribution of glucose hypometabolism. (18)F FDG-PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using Statistical parametric Mapping (SPM). Summed images were preprocessed for statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest (ROI) analysis was performed to validate SPM results. Visual analysis of the (18)F FDG-PET images demonstrated prominent regional glucose hypometabolism in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison using SPM analysis confirmed that the regional distribution of glucose hypo-metabolism was present in thalamus, cerebellum, temporal cortex and central lobule. Two mildly affected patients without epilepsy had hypometabolism in cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose hypometabolism did not correlate with age at the time of PET imaging, head circumference, CSF glucose concentration at the time of diagnosis, RBC glucose uptake, or CNS score. Quantitative analysis of (18)F FDG-PET imaging in Glut1 DS patients confirmed that hypometabolism was present symmetrically in thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus correlated with the clinical history of epilepsy. Copyright © 2014. Published by Elsevier B.V.

Diabetes, impaired fasting glucose, and cognitive decline in a population of elderly community residents.

PubMed

Rouch, Isabelle; Roche, Frédéric; Dauphinot, Virginie; Laurent, Bernard; Antérion, Catherine Thomas; Celle, Sébastien; Krolak-Salmon, Pierre; Barthélémy, Jean-Claude

2012-08-01

Diabetes and impaired fasting glucose, as well as cognitive impairment, are common in the elderly. Although several cross-sectional studies have demonstrated the influence of diabetes on cognitive impairment, only a few longitudinal studies have assessed the relationship between diabetes, impaired fasting glucose and cognitive decline in non-demented elderly community dwellers, by means of extensive neuropsychological batteries. The present study assesses the relationship between baseline diabetes, impaired fasting glucose (IFG) and 2- year evolution of memory, attention and executive performance in a sample of non-demented elderly subjects. Population-based cohort study [(PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF)]. One hundred and sixty-three community dwellers aged 65 years without dementia at recruitment. Memory, attention and executive performance. A significant association was observed between baseline diabetes mellitus and a higher 2-year decline in the Trial Making Test B and Stroop test exploring attention and executive function. This effect remained significant after adjusting for age, gender, education, anxiety and depressive symptoms, as well as other cardiovascular risk factors (F=2.41; p=0.007). Instead, no relationship was observed between IFG and cognitive decline. Our study showed that, in a sample of elderly non-demented community dwellers, diabetes mellitus (but not IFG) is associated with a higher decline in selective attention and executive functioning. These results emphasize the importance of detecting and man- aging diabetes and impaired fasting glucose, in order to prevent cognitive impairment and dementia.

Hypoglycemic effect of cooked Lupinus mutabilis and its purified alkaloids in subjects with type-2 diabetes.

PubMed

Baldeón, M E; Castro, J; Villacrés, E; Narváez, L; Fornasini, M

2012-01-01

Developing countries are experiencing an epidemic of chronic non-communicable chronic diseases with high socio-economic costs. Studies of traditional foods with beneficial health properties could contribute to diminish these problems. Legumes rich in proteins like Lupinus mutabilis decreases blood glucose and improves insulin sensitivity in animals and humans. We report the results of a phase II clinical trial conducted to assess the role of cooked L. mutabilis and its purified alkaloids on blood glucose and insulin in volunteers with diabetes. Results indicate that consumption of cooked L. mutabilis or its purified alkaloids decreased blood glucose and insulin levels. The decreases in serum glucose concentrations from base line to 90 minutes were statistically significant within both treatment groups; however, there were not differences between groups. Serum insulin levels were also decreased in both groups however the differences were not statistically significant. None of the volunteers in either group presented side effects.

Role of viscous guar gums in lowering the glycemic response after a solid meal.

PubMed

Leclère, C J; Champ, M; Boillot, J; Guille, G; Lecannu, G; Molis, C; Bornet, F; Krempf, M; Delort-Laval, J; Galmiche, J P

1994-04-01

The aim of the present study was to investigate how guar gum viscosity acts on starch digestion and glucose absorption in humans. Six healthy subjects received a mixed diet composed of 60.4% carbohydrate in the form of maize glucose or pregelatinized starch, to which was added 5.6% low- or high-viscosity guar gums. Meals were ingested or instilled in the duodenum and postprandial insulin and glucose responses were monitored for 3 h. Infusion of meals containing glucose showed that the delay in the diffusion rate to the duodenal mucosa due to bolus viscosity was not significant. Infusion of meals containing starch showed that a decrease in the digestion rate of starch in the upper small intestine accounted for part of the effect of viscosity on glycemic response, whereas the main effect of guar gum was apparently to slow gastric emptying.

Insulin response to oral glucose in healthy, lean young women and patients with polycystic ovary syndrome.

PubMed

Kulshreshtha, Bindu; Ganie, Mohammed Ashraf; Praveen, Edavan Pulikkanath; Gupta, Nandita; Lal Khurana, Madan; Seith, Ashu; Dwivedi, Sadanand N; Kumar, Guresh; Ammini, Ariachery C

2008-11-01

Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women. In a case-control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion. Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 +/- 4.5 years (range 15-32 years) and their mean body mass index (BMI) was 19.7 +/- 2.6 kg/m(2). Mean blood glucose at 0, 1 and 2 h was 88.2 +/- 7.2, 115.5 +/- 25.5 and 91.8 +/- 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 +/- 1.1, 32.7 +/- 26.5 and 14.6 +/- 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 +/- 3.1, 7.0 +/- 3.1 and 11.4 +/- 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 +/- 0.2. The age of the PCOS women ranged from 15 to 40 years (mean 23.4 +/- 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m(2) (mean 27.7 +/- 6.3 kg/m(2)). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM. Glucose/insulin ratio at 0, 1 and 2 h was lower (8.3 +/- 4.2, 2.0 +/- 1.6 and 3.2 +/- 3.5) than that of healthy controls. HOMA-IR was 3.1 +/- 3.0. Women with PCOS had an exaggerated insulin response to glucose. Thirty-eight percent of PCOS women had some form of abnormal glucose tolerance. Greater insulin response was seen with impairment of glucose tolerance. Obesity had no effect on fasting insulin or insulin response to oral glucose in PCOS women with NGT.

Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.

PubMed

Dudele, Anete; Rasmussen, Gitte Marie; Mayntz, David; Malte, Hans; Lund, Sten; Wang, Tobias

2015-05-01

Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Effects of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas.

PubMed

Hirose, H; Maruyama, H; Ito, K; Seto, Y; Kido, K; Koyama, K; Dan, K; Saruta, T; Kato, R

1994-04-01

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) has a structure which differs from those of other known blood glucose-lowering agents including sulfonylureas. It has been shown that oral administration of A-4166 exerts blood glucose-lowering effects in animal in vivo studies. In the present study, we investigated the effects of A-4166 on insulin and glucagon secretion at several glucose concentrations using isolated perfused rat pancreas preparations. Both 3.0 and 30 mumol/l A-4166 significantly stimulated insulin secretion as compared with basal levels at glucose concentrations of 8.0 and 11.0 mmol (p < 0.01 and p < 0.05, respectively). In contrast, glucagon secretion was not affected by administration of A-4166 up to 30 mumol/l at these glucose concentrations. At a glucose concentration of 5.6 mmol/l, neither 0.3 nor 3.0 mumol/l A-4166 produced significant changes in insulin and glucagon secretion. However, A-4166 at 30 mumol/l significantly stimulated insulin secretion and inhibited glucagon secretion as compared with basal levels (p < 0.01 and p < 0.01, respectively). We conclude that A-4166 at 3.0 and 30 mumol/l directly stimulates insulin secretion but has little effect on glucagon secretion in isolated perfused rat pancreas at glucose concentrations of 8.0 and 11.0 mmol/l. these results, taken together with previously published data, suggest that oral administration of A-4166 could be a useful strategy for stimulating endogenous insulin secretion in non-insulin-dependent diabetic patients.

Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemia.

PubMed

Minami, Asako; Ishimura, Noriko; Sakamoto, Sadaichi; Takishita, Eiko; Mawatari, Kazuaki; Okada, Kazuko; Nakaya, Yutaka

2002-02-01

The purpose of the present study was to test whether hyperlipidaemia and insulin resistance in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats can be improved by dietary supplementation with purified eicosapentaenoic acid (EPA) or oleic acid (OA). Male OLETF rats were fed powdered chow (510 g fat/kg) alone (n 8) or chow supplemented with 10 g EPA- (n 8) or OA- (n 8) rich oil/kg per d from 5 weeks until 30 weeks of age. An oral glucose tolerance test and hyperinsulinaemic euglycaemic clamp was performed at 25 and 30 weeks of age. EPA supplementation resulted in significantly (P<0.05) reduced plasma lipids, hepatic triacylglycerols, and abdominal fat deposits, and more efficient in vivo glucose disposal compared with OA supplementation and no supplementation. OA supplementation was associated with significantly increased insulin response to oral glucose compared with EPA supplementation and no supplementation. Inverse correlation was noted between glucose uptake and plasma triacylglycerol levels (r -086, P<0.001) and abdominal fat volume (r -0.80, P<0.001). The result of oral glucose tolerance test study showed that the rats fed EPA tended to improve glucose intolerance, although this was not statistically significant. Levels of plasma insulin at 60 min after glucose was significantly increased in rats fed OA compared with the other two groups. The results indicate that long-term feeding of EPA might be effective in preventing insulin resistance in diabetes-prone rats, at least in part, due to improving hypertriacylglycerolaemia.

Time delay compensation for closed-loop insulin delivery systems: a simulation study.

PubMed

Reboldi, G P; Home, P D; Calabrese, G; Fabietti, P G; Brunetti, P; Massi Benedetti, M

1991-06-01

Closed loop insulin therapy certainly represents the best possible approach to insulin replacement. However, present limitations preclude wider application of the so-called artificial pancreas. Therefore, a thorough understanding of these limitations is needed to design better systems for future long-term use. The present simulation study was design: to obtain better information on the impact of the measurement delay of currently available closed-loop devices both during closed-loop insulin delivery and blood glucose clamp studies, and to design and test a time delay compensator based on the method originally described by O.J. Smith. Simulations were performed on a Compaq Deskpro 486/25 personal computer under MS-DOS operating system using Simnon rel. 3.00 software. There was a direct relationship between measurement delay and amount of insulin delivered, i.e., the longer the delay the higher the insulin dose needed to control a rise in blood glucose; the closed-loop response in presence of a time delay was qualitatively impaired both during insulin delivery and blood glucose clamp studies; time delay compensation was effective in reducing the insulin dose and improving controller stability during the early phase of clamp studies. However, the robustness of a Smith's predictor-based controller should be carefully evaluated before implementation in closed-loop systems can be considered.

Glucose as the Sole Metabolic Fuel: A Study on the Possible Influence of Teachers' Knowledge on the Establishment of a Misconception among Brazilian High School Students

ERIC Educational Resources Information Center

da Luz, Mauricio Roberto Motta Pinto

2008-01-01

In the present work, I investigated the origin of the misconception that glucose is the sole metabolic fuel previously described among Brazilian high school students. The results of a multiple-choice test composed of 24 questions about a broad range of biology subjects were analyzed. The test was part of a contest and was answered by a sample…

A Disposable Tear Glucose Biosensor—Part 2: System Integration and Model Validation

PubMed Central

La Belle, Jeffrey T.; Bishop, Daniel K.; Vossler, Stephen R.; Patel, Dharmendra R.; Cook, Curtiss B.

2010-01-01

Background We presented a concept for a tear glucose sensor system in an article by Bishop and colleagues in this issue of Journal of Diabetes Science and Technology. A unique solution to collect tear fluid and measure glucose was developed. Individual components were selected, tested, and optimized, and system error modeling was performed. Further data on prototype testing are now provided. Methods An integrated fluidics portion of the prototype was designed, cast, and tested. A sensor was created using screen-printed sensors integrated with a silicone rubber fluidics system and absorbent polyurethane foam. A simulated eye surface was prepared using fluid-saturated poly(2-hydroxyethyl methacrylate) sheets, and the disposable prototype was tested for both reproducibility at 0, 200, and 400 μM glucose (n = 7) and dynamic range of glucose detection from 0 to 1000 μM glucose. Results From the replicated runs, an established relative standard deviation of 15.8% was calculated at 200 μM and a lower limit of detection was calculated at 43.4 μM. A linear dynamic range was demonstrated from 0 to 1000 μM with an R2 of 99.56%. The previously developed model predicted a 14.9% variation. This compares to the observed variance of 15.8% measured at 200 μM glucose. Conclusion With the newly designed fluidics component, an integrated tear glucose prototype was assembled and tested. Testing of this integrated prototype demonstrated a satisfactory lower limit of detection for measuring glucose concentration in tears and was reproducible across a physiological sampling range. The next step in the device design process will be initial animal studies to evaluate the current prototype for factors such as eye irritation, ease of use, and correlation with blood glucose. PMID:20307390

A disposable tear glucose biosensor-part 2: system integration and model validation.

PubMed

La Belle, Jeffrey T; Bishop, Daniel K; Vossler, Stephen R; Patel, Dharmendra R; Cook, Curtiss B

2010-03-01

We presented a concept for a tear glucose sensor system in an article by Bishop and colleagues in this issue of Journal of Diabetes Science and Technology. A unique solution to collect tear fluid and measure glucose was developed. Individual components were selected, tested, and optimized, and system error modeling was performed. Further data on prototype testing are now provided. An integrated fluidics portion of the prototype was designed, cast, and tested. A sensor was created using screen-printed sensors integrated with a silicone rubber fluidics system and absorbent polyurethane foam. A simulated eye surface was prepared using fluid-saturated poly(2-hydroxyethyl methacrylate) sheets, and the disposable prototype was tested for both reproducibility at 0, 200, and 400 microM glucose (n = 7) and dynamic range of glucose detection from 0 to 1000 microM glucose. From the replicated runs, an established relative standard deviation of 15.8% was calculated at 200 microM and a lower limit of detection was calculated at 43.4 microM. A linear dynamic range was demonstrated from 0 to 1000 microM with an R(2) of 99.56%. The previously developed model predicted a 14.9% variation. This compares to the observed variance of 15.8% measured at 200 microM glucose. With the newly designed fluidics component, an integrated tear glucose prototype was assembled and tested. Testing of this integrated prototype demonstrated a satisfactory lower limit of detection for measuring glucose concentration in tears and was reproducible across a physiological sampling range. The next step in the device design process will be initial animal studies to evaluate the current prototype for factors such as eye irritation, ease of use, and correlation with blood glucose. (c) 2010 Diabetes Technology Society.

Apelin targets gut contraction to control glucose metabolism via the brain.

PubMed

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-02-01

The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects of dietary cis and trans unsaturated and saturated fatty acids on the glucose metabolites and enzymes of rats.

PubMed

Bernal, Claudio A; Rovira, Jordi; Colandré, María E; Cussó, Roser; Cadefau, Joan A

2006-05-01

The aim of the present study was to examine whether the level of dietary cis fatty acid (cFA), or the isomers (trans or cis) and/or the saturation of the fatty acids at high dietary fat levels altered the intracellular glucose metabolites and certain regulatory enzyme activities in the skeletal muscle and liver of rats. The animals were fed for 30 d on either a recommended control diet (7 % cFA, w/w) or a high-fat diet (20 % fatty acids, w/w). The high-fat diet was enriched with either cFA, trans fatty acid (tFA), a moderate proportion of saturated fatty acid (MSFA), or a high proportion of saturated fatty acid (HSFA). The most striking findings were observed in the gastrocnemius muscle with a HSFA diet. There was a significant increase in glucose-6-phosphate (306 %), glucose-1-phosphate (245 %), fructose-6-phosphate (400 %), fructose-1,6-bisphosphate (86 %), glyceraldehyde-3-phosphate (38 %), pyruvate (341 %), lactate (325 %), citrate (79 %) and the bisphosphorylated sugars as compared with the cFA diet. These changes were paralleled by an increase in muscle triacylglycerol content (49 %) and a decrease in glucose (39 %). In addition, the amount of cFA and the other types of fatty acid (i.e. tFA and MSFA) led to no great differences in glucose metabolism as compared with the respective control group. These data support the hypothesis that glucose changes induced by a HSFA diet are a multifaceted abnormality. Glucose and lactate transport and intracellular glucose metabolism could be the key biochemical defects involved in this detrimental effect on glucose metabolism.

Hypoglycemia early alarm systems based on recursive autoregressive partial least squares models.

PubMed

Bayrak, Elif Seyma; Turksoy, Kamuran; Cinar, Ali; Quinn, Lauretta; Littlejohn, Elizabeth; Rollins, Derrick

2013-01-01

Hypoglycemia caused by intensive insulin therapy is a major challenge for artificial pancreas systems. Early detection and prevention of potential hypoglycemia are essential for the acceptance of fully automated artificial pancreas systems. Many of the proposed alarm systems are based on interpretation of recent values or trends in glucose values. In the present study, subject-specific linear models are introduced to capture glucose variations and predict future blood glucose concentrations. These models can be used in early alarm systems of potential hypoglycemia. A recursive autoregressive partial least squares (RARPLS) algorithm is used to model the continuous glucose monitoring sensor data and predict future glucose concentrations for use in hypoglycemia alarm systems. The partial least squares models constructed are updated recursively at each sampling step with a moving window. An early hypoglycemia alarm algorithm using these models is proposed and evaluated. Glucose prediction models based on real-time filtered data has a root mean squared error of 7.79 and a sum of squares of glucose prediction error of 7.35% for six-step-ahead (30 min) glucose predictions. The early alarm systems based on RARPLS shows good performance. A sensitivity of 86% and a false alarm rate of 0.42 false positive/day are obtained for the early alarm system based on six-step-ahead predicted glucose values with an average early detection time of 25.25 min. The RARPLS models developed provide satisfactory glucose prediction with relatively smaller error than other proposed algorithms and are good candidates to forecast and warn about potential hypoglycemia unless preventive action is taken far in advance. © 2012 Diabetes Technology Society.

Understanding the native Californian diet: Identification of condensed and hydrolyzable tannins in tanoak acorns (Lithocarpus densiflorus).

PubMed

Meyers, Katherine J; Swiecki, Tedmund J; Mitchell, Alyson E

2006-10-04

The tanoak (Lithocarpus densiflorus) acorn was a staple food in the Native American diet and is still used in traditional dishes. Acorns from the genus Quercus have been shown to contain a large range of hydrolyzable tannins. However, neither hydrolyzable nor condensed tannins have been characterized in tanoak acorns. The aim of this study was to identify the full range of hydrolyzable and condensed tannins in extracts of tanoak acorns using liquid chromatography/electrospray ionization-mass spectrometry/mass spectrometry. Condensed tannins were identified as B type oligomers of (epi)-catechin (procyanidins) with a degree of polymerization up to six. Oligomers up to and including tetramers were identified by UV spectra and MS detection whereas pentamers and hexamers were detected only by MS. The total concentration of condensed tannins was 464 mg/100 g acorn pericarp. The concentration of propocyanidin monomers, dimers, trimers, and tetramers in acorn pericarp (mg/100 g acorn pericarp) were 95 +/- 10.9, 148 +/- 35.0, 90 +/- 17.9, and 131 +/- 1.9, respectively. No procyanidins were found in the acorn cotyledon tissue. A total of 22 hydrolyzable tannins were identified in methanolic extracts of acorn cotyledon tissue. Gallic acid derivatives predominated and included galloylated esters of glucose, hexahydrodiphenoyl esters of glucose, and methylated gallates. Galloylated esters of glucose were present as isomers of galloyl glucose, digalloyl glucose, and trigalloyl glucose. Mass spectral fragmentation patterns indicate the presence of one gallic acid-galloyl glucose isomer and two gallic acid-digalloyl-glucose isomers. No isomers of tetragalloyl glucose and pentagalloyl glucose were identified. Ellagic acid and ellagic acid pentoside were also identified.

The self-aware diabetic patient software agent model.

PubMed

Wang, Zhanle; Paranjape, Raman

2013-11-01

This work presents a self-aware diabetic patient software agent for representing a human diabetic patient. To develop a 24h, stochastic and self-aware patient agent, we extend the original seminal work of Ackerman et al. [1] in creating a mathematical model of human blood glucose levels in three aspects. (1) We incorporate the stochastic and unpredictable effects of daily living. (2) The Ackerman model is extended into the period of night-time. (3) Patients' awareness of their own conditions is incorporated. Simulation results are quantitatively assessed to demonstrate the effectiveness of lifestyle management, such as adjusting the amount of food consumed, meal schedule, intensity of exercise and level of medication. In this work we show through the simulation that the average blood glucose can be reduced by as much as 51% due to careful lifestyle management. Self monitoring blood glucose is also quantitatively evaluated. The simulation results show that the average blood glucose is further dropped by 25% with the assistance of blood glucose samples. In addition, the blood glucose is perfectly controlled in the target range during the simulation period as a result of joint efforts of lifestyle management and self monitoring blood glucose. This study focuses on demonstrating how human patients' behavior, specifically lifestyle and self monitoring of blood glucose, affects blood glucose controls on a daily basis. This work does not focus on the insulin-glucose interaction of an individual human patient. Our conclusion is that this self-aware patient agent model is capable of adequately representing diabetic patients and of evaluating their dynamic behaviors. It can also be incorporated into a multi-agent system by introducing other healthcare components so that more interesting insights such as the healthcare quality, cost and performance can be observed. © 2013 Published by Elsevier Ltd.

Hypoglycemia Early Alarm Systems Based on Recursive Autoregressive Partial Least Squares Models

PubMed Central

Bayrak, Elif Seyma; Turksoy, Kamuran; Cinar, Ali; Quinn, Lauretta; Littlejohn, Elizabeth; Rollins, Derrick

2013-01-01

Background Hypoglycemia caused by intensive insulin therapy is a major challenge for artificial pancreas systems. Early detection and prevention of potential hypoglycemia are essential for the acceptance of fully automated artificial pancreas systems. Many of the proposed alarm systems are based on interpretation of recent values or trends in glucose values. In the present study, subject-specific linear models are introduced to capture glucose variations and predict future blood glucose concentrations. These models can be used in early alarm systems of potential hypoglycemia. Methods A recursive autoregressive partial least squares (RARPLS) algorithm is used to model the continuous glucose monitoring sensor data and predict future glucose concentrations for use in hypoglycemia alarm systems. The partial least squares models constructed are updated recursively at each sampling step with a moving window. An early hypoglycemia alarm algorithm using these models is proposed and evaluated. Results Glucose prediction models based on real-time filtered data has a root mean squared error of 7.79 and a sum of squares of glucose prediction error of 7.35% for six-step-ahead (30 min) glucose predictions. The early alarm systems based on RARPLS shows good performance. A sensitivity of 86% and a false alarm rate of 0.42 false positive/day are obtained for the early alarm system based on six-step-ahead predicted glucose values with an average early detection time of 25.25 min. Conclusions The RARPLS models developed provide satisfactory glucose prediction with relatively smaller error than other proposed algorithms and are good candidates to forecast and warn about potential hypoglycemia unless preventive action is taken far in advance. PMID:23439179

Salivary glucose concentration and excretion in normal and diabetic subjects.

PubMed

Jurysta, Cedric; Bulur, Nurdan; Oguzhan, Berrin; Satman, Ilhan; Yilmaz, Temel M; Malaisse, Willy J; Sener, Abdullah

2009-01-01

The present report aims mainly at a reevaluation of salivary glucose concentration and excretion in unstimulated and mechanically stimulated saliva in both normal and diabetic subjects. In normal subjects, a decrease in saliva glucose concentration, an increase in salivary flow, but an unchanged glucose excretion rate were recorded when comparing stimulated saliva to unstimulated saliva. In diabetic patients, an increase in salivary flow with unchanged salivary glucose concentration and glucose excretion rate were observed under the same experimental conditions. Salivary glucose concentration and excretion were much higher in diabetic patients than in control subjects, whether in unstimulated or stimulated saliva. No significant correlation between glycemia and either glucose concentration or glucose excretion rate was found in the diabetic patients, whether in unstimulated or stimulated saliva. In the latter patients, as compared to control subjects, the relative magnitude of the increase in saliva glucose concentration was comparable, however, to that of blood glucose concentration. The relationship between these two variables was also documented in normal subjects and diabetic patients undergoing an oral glucose tolerance test.

The effects of glucose dose and dual-task performance on memory for emotional material.

PubMed

Brandt, Karen R; Sünram-Lea, Sandra I; Jenkinson, Paul M; Jones, Emma

2010-07-29

Whilst previous research has shown that glucose administration can boost memory performance, research investigating the effects of glucose on memory for emotional material has produced mixed findings. Whereas some research has shown that glucose impairs memory for emotional material, other research has shown that glucose has no effect on emotional items. The aim of the present research was therefore to provide further investigation of the role of glucose on the recognition of words with emotional valence by exploring effects of dose and dual-task performance, both of which affect glucose facilitation effects. The results replicated past research in showing that glucose administration, regardless of dose or dual-task conditions, did not affect the memorial advantage enjoyed by emotional material. This therefore suggests an independent relationship between blood glucose levels and memory for emotional material. Copyright 2010 Elsevier B.V. All rights reserved.

Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring.

PubMed

Chen, Yihao; Lu, Siyuan; Zhang, Shasha; Li, Yan; Qu, Zhe; Chen, Ying; Lu, Bingwei; Wang, Xinyan; Feng, Xue

2017-12-01

Currently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement accuracy, weak blood glucose correlation, and inability to detect hyperglycemia/hypoglycemia during sleep. We present a strategy to design and fabricate a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery-powered electrochemical twin channels (ETCs). The designed subcutaneous ETCs drive intravascular blood glucose out of the vessel and transport it to the skin surface. The ultrathin (~3 μm) nanostructured biosensor, with high sensitivity (130.4 μA/mM), fully absorbs and measures the glucose, owing to its extreme conformability. We conducted in vivo human clinical trials. The noninvasive measurement results for intravascular blood glucose showed a high correlation (>0.9) with clinically measured blood glucose levels. The system opens up new prospects for clinical-grade noninvasive continuous glucose monitoring.

Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring

PubMed Central

Chen, Yihao; Lu, Siyuan; Zhang, Shasha; Li, Yan; Qu, Zhe; Chen, Ying; Lu, Bingwei; Wang, Xinyan; Feng, Xue

2017-01-01

Currently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement accuracy, weak blood glucose correlation, and inability to detect hyperglycemia/hypoglycemia during sleep. We present a strategy to design and fabricate a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery–powered electrochemical twin channels (ETCs). The designed subcutaneous ETCs drive intravascular blood glucose out of the vessel and transport it to the skin surface. The ultrathin (~3 μm) nanostructured biosensor, with high sensitivity (130.4 μA/mM), fully absorbs and measures the glucose, owing to its extreme conformability. We conducted in vivo human clinical trials. The noninvasive measurement results for intravascular blood glucose showed a high correlation (>0.9) with clinically measured blood glucose levels. The system opens up new prospects for clinical-grade noninvasive continuous glucose monitoring. PMID:29279864

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vikram, Ajit; Jena, Gopabandhu, E-mail: gbjena@gmail.com

Research highlights: {yields}Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. {yields}Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. {yields}Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. {yields}Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report thatmore » S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia ({approx}18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPAR{gamma}) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 {+-} 16.32 vs. 126.37 {+-} 27.07 mg/dl) and glucose intolerance ({approx}78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.« less

[The research of near-infrared blood glucose measurement using particle swarm optimization and artificial neural network].

PubMed

Dai, Juan; Ji, Zhong; Du, Yubao

2017-08-01

Existing near-infrared non-invasive blood glucose detection modelings mostly detect multi-spectral signals with different wavelength, which is not conducive to the popularization of non-invasive glucose meter at home and does not consider the physiological glucose dynamics of individuals. In order to solve these problems, this study presented a non-invasive blood glucose detection model combining particle swarm optimization (PSO) and artificial neural network (ANN) by using the 1 550 nm near-infrared absorbance as the independent variable and the concentration of blood glucose as the dependent variable, named as PSO-2ANN. The PSO-2ANN model was based on two sub-modules of neural networks with certain structures and arguments, and was built up after optimizing the weight coefficients of the two networks by particle swarm optimization. The results of 10 volunteers were predicted by PSO-2ANN. It was indicated that the relative error of 9 volunteers was less than 20%; 98.28% of the predictions of blood glucose by PSO-2ANN were distributed in the regions A and B of Clarke error grid, which confirmed that PSO-2ANN could offer higher prediction accuracy and better robustness by comparison with ANN. Additionally, even the physiological glucose dynamics of individuals may be different due to the influence of environment, temper, mental state and so on, PSO-2ANN can correct this difference only by adjusting one argument. The PSO-2ANN model provided us a new prospect to overcome individual differences in blood glucose prediction.

A discrete mathematical model applied to genetic regulation and metabolic networks.

PubMed

Asenjo, A J; Ramirez, P; Rapaport, I; Aracena, J; Goles, E; Andrews, B A

2007-03-01

This paper describes the use of a discrete mathematical model to represent the basic mechanisms of regulation of the bacteria E. coli in batch fermentation. The specific phenomena studied were the changes in metabolism and genetic regulation when the bacteria use three different carbon substrates (glucose, glycerol, and acetate). The model correctly predicts the behavior of E. coli vis-à-vis substrate mixtures. In a mixture of glucose, glycerol, and acetate, it prefers glucose, then glycerol, and finally acetate. The model included 67 nodes; 28 were genes, 20 enzymes, and 19 regulators/biochemical compounds. The model represents both the genetic regulation and metabolic networks in an inrtegrated form, which is how they function biologically. This is one of the first attempts to include both of these networks in one model. Previously, discrete mathematical models were used only to describe genetic regulation networks. The study of the network dynamics generated 8 (2(3)) fixed points, one for each nutrient configuration (substrate mixture) in the medium. The fixed points of the discrete model reflect the phenotypes described. Gene expression and the patterns of the metabolic fluxes generated are described accurately. The activation of the gene regulation network depends basically on the presence of glucose and glycerol. The model predicts the behavior when mixed carbon sources are utilized as well as when there is no carbon source present. Fictitious jokers (Joker1, Joker2, and Repressor SdhC) had to be created to control 12 genes whose regulation mechanism is unknown, since glycerol and glucose do not act directly on the genes. The approach presented in this paper is particularly useful to investigate potential unknown gene regulation mechanisms; such a novel approach can also be used to describe other gene regulation situations such as the comparison between non-recombinant and recombinant yeast strain, producing recombinant proteins, presently under investigation in our group.

Risk factors for Type 2 Diabetes Mellitus in college students: association with sociodemographic variables1

PubMed Central

Lima, Adman Câmara Soares; Araújo, Márcio Flávio Moura; de Freitas, Roberto Wagner Júnior Freire; Zanetti, Maria Lúcia; de Almeida, Paulo César; Damasceno, Marta Maria Coelho

2014-01-01

Objective identify the modifiable risk factors for type 2 diabetes mellitus in college students and associate these factors with their sociodemographic variables. Method cross-sectional study, involving 702 college students from Fortaleza-CE, Brazil. Sociodemographic, anthropometric, physical exercise data and blood pressure and fasting plasma glucose levels were collected. Results the most prevalent risk factor was sedentariness, followed by overweight, central obesity, high fasting plasma glucose and arterial hypertension. A statistically significant association was found between overweight and sex (p=0.000), age (p=0.004) and marital status (p=0.012), as well as between central obesity and age (p=0.018) and marital status (p=0.007) and between high fasting plasma glucose and sex (p=0.033). Conclusion distinct risk factors were present in the study population, particularly sedentariness and overweight. PMID:25029061

13C, 2H NMR Studies of Structural and Dynamical Modifications of Glucose-Exposed Porcine Aortic Elastin

PubMed Central

Silverstein, Moshe C.; Bilici, Kübra; Morgan, Steven W.; Wang, Yunjie; Zhang, Yanhang; Boutis, Gregory S.

2015-01-01

Elastin, the principal component of the elastic fiber of the extracellular matrix, imparts to vertebrate tissues remarkable resilience and longevity. This work focuses on elucidating dynamical and structural modifications of porcine aortic elastin exposed to glucose by solid-state NMR spectroscopic and relaxation methodologies. Results from macroscopic stress-strain tests are also presented and indicate that glucose-treated elastin is mechanically stiffer than the same tissue without glucose treatment. These measurements show a large hysteresis in the stress-strain behavior of glucose-treated elastin—a well-known signature of viscoelasticity. Two-dimensional relaxation NMR methods were used to investigate the correlation time, distribution, and population of water in these samples. Differences are observed between the relative populations of water, whereas the measured correlation times of tumbling motion of water across the samples were similar. 13C magic-angle-spinning NMR methods were applied to investigate structural and dynamical modifications after glucose treatment. Although some overall structure is preserved, the process of glucose exposure results in more heterogeneous structures and slower mobility. The correlation times of tumbling motion of the 13C-1H internuclear vectors in the glucose-treated sample are larger than in untreated samples, pointing to their more rigid structure. The 13C cross-polarization spectra reveal a notably increased α-helical character in the alanine motifs after glucose exposure. Results from molecular dynamics simulations are provided that add further insight into dynamical and structural changes of a short repeat, [VPGVG]5, an alanine pentamer, desmosine, and isodesmosine sites with and without glucose. The simulations point to changes in the entropic and energetic contributions in the retractive forces of VPGVG and AAAAA motifs. The most notable change is the increase of the energetic contribution in the retractive force due to peptide-glucose interactions of the VPGVG motif, which may play an important role in the observed stiffening in glucose-treated elastin. PMID:25863067

Antihyperglycemic activities of leaves of three edible fruit plants (Averrhoa carambola, Ficus hispida and Syzygium samarangense) of Bangladesh.

PubMed

Shahreen, Shejuty; Banik, Joyanta; Hafiz, Abdul; Rahman, Shahnaz; Zaman, Anahita Tanzia; Shoyeb, Md Abu; Chowdhury, Majeedul H; Rahmatullah, Mohammed

2012-01-01

Averrhoa carambola L. (Oxalidaceae), Ficus hispida L.f. (Moraceae), and Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae) are three common plants in Bangladesh, the fruits of which are edible. The leaves and fruits of A. carambola and F. hispida are used by folk medicinal practitioners for treatment of diabetes, while the leaves of S. samarangense are used for treatment of cold, itches, and waist pain. Since scientific studies are absent on the antihyperglycemic effects of the leaves of the three plants, it was the objective of the present study to evaluate the antihyperglycemic potential of methanolic extract of leaves of the plants in oral glucose tolerance tests carried out with glucose-loaded mice. The extracts at different doses were administered one hour prior to glucose administration and blood glucose level was measured after two hours of glucose administration (p.o.) using glucose oxidase method. Significant oral hypoglycemic activity was found with the extracts of leaves of all three plants tested. The fall in serum glucose levels were dose-dependent for every individual plant, being highest at the highest dose tested of 400 mg extract per kg body weight. At this dose, the extracts of A. carambola, F. hispida, and S. samarangense caused, respectively, 34.1, 22.7, and 59.3% reductions in serum glucose levels when compared to control animals. The standard antihyperglycemic drug, glibenclamide, caused a 57.3% reduction in serum glucose levels versus control. Among the three plants evaluated, the methanolic extract of leaves of S. samarangense proved to be the most potent in demonstrating antihyperglycemic effects. The result validates the folk medicinal uses of A. carambola and F. hispida in the treatment of diabetes, and indicates that the leaves of S. samarangense can also possibly be used for amelioration of diabetes-induced hyperglycemia.

Brain glucose and acetoacetate metabolism: a comparison of young and older adults.

PubMed

Nugent, Scott; Tremblay, Sebastien; Chen, Kewei W; Ayutyanont, Napatkamon; Roontiva, Auttawut; Castellano, Christian-Alexandre; Fortier, Melanie; Roy, Maggie; Courchesne-Loyer, Alexandre; Bocti, Christian; Lepage, Martin; Turcotte, Eric; Fulop, Tamas; Reiman, Eric M; Cunnane, Stephen C

2014-06-01

The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

Ex vivo generation of glucose sensitive insulin secreting mesenchymal stem cells derived from human adipose tissue.

PubMed

Dave, Shruti D; Vanikar, Aruna V; Trivedi, Hargovind L

2012-03-01

Diabetics are incapable of producing insulin/have autoimmune mechanisms making it ineffective to control glucose secretion. We present a prospective study of glucose-sensitive insulin-secreting mesenchymal stem cells (IS-MSC) generated from human adipose tissue (h-AD) sans xenogenic material. Ten grams h-AD from donor anterior abdominal wall was collected in proliferation medium composed of α-Minimum Essential Media (α-MEM), albumin, fibroblast-growth factor and antibiotics, minced, incubated in collagenase-I at 37°C with shaker and centrifuged. Supernatant and pellets were separately cultured in proliferation medium on cell+ plates at 37°C with 5% CO(2) for 10 days. Cells were harvested by trypsinization, checked for viability, sterility, counts, flow-cytometry (CD45(-)/90(+)/73(+)), and differentiated into insulin-expressing cells using medium composed of DMEM, gene expressing up-regulators and antibiotics for 3 days. They were studied for transcriptional factors Pax-6, Isl-1, pdx-1 (immunofluorescence). C-peptide and insulin were measured by chemiluminescence. In vitro glucose sensitivity assay was carried out by measuring levels of insulin and C-peptide secretion in absence of glucose followed by 2 hours incubation after glucose addition. Mean IS-AD-MSC quantum was 3.21 ml, cell count, 1.5 ×10(3) cells/μl), CD45(-)/90(+)/73(+) cells were 44.37% /25.52%. All of them showed presence of pax-6, pdx-1, and Isl-1. Mean C-Peptide and insulin levels were 0.36 ng/ml and 234 μU/ml, respectively, pre-glucose and 0.87 ng/ml and 618.3 μU/ml post-glucose additions. The mean rise in secretion levels was 2.42 and 2.65 fold, respectively. Insulin-secreting h-AD-MSC can be generated safely and effectively showing in vitro glucose responsive alteration in insulin and C-peptide secretion levels.

Modelling the growth kinetics of Kocuria marina DAGII as a function of single and binary substrate during batch production of β-Cryptoxanthin.

PubMed

Mitra, Ruchira; Chaudhuri, Surabhi; Dutta, Debjani

2017-01-01

In the present investigation, growth kinetics of Kocuria marina DAGII during batch production of β-Cryptoxanthin (β-CRX) was studied by considering the effect of glucose and maltose as a single and binary substrate. The importance of mixed substrate over single substrate has been emphasised in the present study. Different mathematical models namely, the Logistic model for cell growth, the Logistic mass balance equation for substrate consumption and the Luedeking-Piret model for β-CRX production were successfully implemented. Model-based analyses for the single substrate experiments suggested that the concentrations of glucose and maltose higher than 7.5 and 10.0 g/L, respectively, inhibited the growth and β-CRX production by K. marina DAGII. The Han and Levenspiel model and the Luong product inhibition model accurately described the cell growth in glucose and maltose substrate systems with a R 2 value of 0.9989 and 0.9998, respectively. The effect of glucose and maltose as binary substrate was further investigated. The binary substrate kinetics was well described using the sum-kinetics with interaction parameters model. The results of production kinetics revealed that the presence of binary substrate in the cultivation medium increased the biomass and β-CRX yield significantly. This study is a first time detailed investigation on kinetic behaviours of K. marina DAGII during β-CRX production. The parameters obtained in the study might be helpful for developing strategies for commercial production of β-CRX by K. marina DAGII.

Effect of styrene exposure on plasma parameters, molecular mechanisms and gene expression in rat model islet cells.

PubMed

Niaz, Kamal; Hassan, Fatima Ismail; Mabqool, Faheem; Khan, Fazlullah; Momtaz, Saeideh; Baeeri, Maryam; Navaei-Nigjeh, Mona; Rahimifard, Mahban; Abdollahi, Mohammad

2017-09-01

Styrene is an aromatic hydrocarbon compound present in the environment and have primary exposure through plastic industry. The current study was designed to evaluate styrene-induced toxicity parameters in rat plasma fasting blood glucose (FBG) level, oral glucose tolerance, insulin secretion, oxidative stress, and inflammatory cytokines in cellular and molecular levels. Styrene was dissolved in corn oil and administered at different doses (250, 500, 1000, 1500, 2000mg/kg/day and control) to each rat, for 42days. In treated groups, styrene significantly increased fasting blood glucose, plasma insulin (p<0.001) and glucose tolerance. Glucose tolerance, insulin resistance and hyperglycemia were found to be the main consequences correlating gene expression of islet cells. Styrene caused a significant enhancement of oxidative stress markers (p<0.001) and inflammatory cytokines in a dose and concentration-dependent manner in plasma (p<0.001). Moreover, the activities of caspase-3 and -9 of the islet cells were significantly up-regulated by this compound at 1500 and 2000mg/kg/day styrene administrated groups (p<0.001). The relative fold change of GLUD1 was downregulated (p<0.05) and upregulated at 1500 and 2000mg/kg, respectively (p<0.01). The relative fold changes of GLUT2 were down regulated at 250 and 1000mg/kg and up regulated in 500, 1500 and 2000mg/kg doses of styrene (p<0.01). The expression level of GCK indicated a significant upregulation at 250mg/kg and downregulation of relative fold changes in the remaining doses of styrene, except for no change at 2000mg/kg of styrene for GCK. Targeting genes (GLUD1, GLUT2 and GCK) of the pancreatic islet cells in styrene exposed groups, disrupted gluconeogenesis, glycogenolysis pathways and insulin secretory functions. The present study illustrated that fasting blood glucose, insulin pathway, oxidative balance, inflammatory cytokines, cell viability and responsible genes of glucose metabolism are susceptible to styrene, which consequently lead to other abnormalities in various organs. Copyright © 2017 Elsevier B.V. All rights reserved.

Microcirculation and its relation to continuous subcutaneous glucose sensor accuracy in cardiac surgery patients in the intensive care unit.

PubMed

Siegelaar, Sarah E; Barwari, Temo; Hermanides, Jeroen; van der Voort, Peter H J; Hoekstra, Joost B L; DeVries, J Hans

2013-11-01

Continuous glucose monitoring could be helpful for glucose regulation in critically ill patients; however, its accuracy is uncertain and might be influenced by microcirculation. We investigated the microcirculation and its relation to the accuracy of 2 continuous glucose monitoring devices in patients after cardiac surgery. The present prospective, observational study included 60 patients admitted for cardiac surgery. Two continuous glucose monitoring devices (Guardian Real-Time and FreeStyle Navigator) were placed before surgery. The relative absolute deviation between continuous glucose monitoring and the arterial reference glucose was calculated to assess the accuracy. Microcirculation was measured using the microvascular flow index, perfused vessel density, and proportion of perfused vessels using sublingual sidestream dark-field imaging, and tissue oxygenation using near-infrared spectroscopy. The associations were assessed using a linear mixed-effects model for repeated measures. The median relative absolute deviation of the Navigator was 11% (interquartile range, 8%-16%) and of the Guardian was 14% (interquartile range, 11%-18%; P = .05). Tissue oxygenation significantly increased during the intensive care unit admission (maximum 91.2% [3.9] after 6 hours) and decreased thereafter, stabilizing after 20 hours. A decrease in perfused vessel density accompanied the increase in tissue oxygenation. Microcirculatory variables were not associated with sensor accuracy. A lower peripheral temperature (Navigator, b = -0.008, P = .003; Guardian, b = -0.006, P = .048), and for the Navigator, also a higher Acute Physiology and Chronic Health Evaluation IV predicted mortality (b = 0.017, P < .001) and age (b = 0.002, P = .037) were associated with decreased sensor accuracy. The results of the present study have shown acceptable accuracy for both sensors in patients after cardiac surgery. The microcirculation was impaired to a limited extent compared with that in patients with sepsis and healthy controls. This impairment was not related to sensor accuracy but the peripheral temperature for both sensors and patient age and Acute Physiology and Chronic Health Evaluation IV predicted mortality for the Navigator were. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Effects of clenbuterol on insulin resistance in conscious obese Zucker rats.

PubMed

Pan, S J; Hancock, J; Ding, Z; Fogt, D; Lee, M; Ivy, J L

2001-04-01

The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.

Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

PubMed

Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, Hakam; Sonnewald, Ursula

2002-02-01

This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.

In Vivo Glucose Monitoring Using Dual-Wavelength Polarimetry to Overcome Corneal Birefringence in the Presence of Motion

PubMed Central

Malik, Bilal H.; Gresham, Vincent C.; Coté, Gerard L.

2012-01-01

Abstract Objective Over the past 35 years considerable research has been performed toward the investigation of noninvasive and minimally invasive glucose monitoring techniques. Optical polarimetry is one noninvasive technique that has shown promise as a means to ascertain blood glucose levels through measuring the glucose concentrations in the anterior chamber of the eye. However, one of the key limitations to the use of optical polarimetry as a means to noninvasively measure glucose levels is the presence of sample noise caused by motion-induced time-varying corneal birefringence. Research Design and Methods In this article our group presents, for the first time, results that show dual-wavelength polarimetry can be used to accurately detect glucose concentrations in the presence of motion-induced birefringence in vivo using New Zealand White rabbits. Results In total, nine animal studies (three New Zealand White rabbits across three separate days) were conducted. Using the dual-wavelength optical polarimetric approach, in vivo, an overall mean average relative difference of 4.49% (11.66 mg/dL) was achieved with 100% Zone A+B hits on a Clarke error grid, including 100% falling in Zone A. Conclusions The results indicate that dual-wavelength polarimetry can effectively be used to significantly reduce the noise due to time-varying corneal birefringence in vivo, allowing the accurate measurement of glucose concentration in the aqueous humor of the eye and correlating that with blood glucose. PMID:22691020

High glucose upregulates BACE1-mediated Aβ production through ROS-dependent HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization in SK-N-MC cells

PubMed Central

Lee, Hyun Jik; Ryu, Jung Min; Jung, Young Hyun; Lee, Sei-Jung; Kim, Jeong Yeon; Lee, Sang Hun; Hwang, In Koo; Seong, Je Kyung; Han, Ho Jae

2016-01-01

There is an accumulation of evidence indicating that the risk of Alzheimer’s disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (Aβ), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated Aβ secretion and apoptosis in a dose-dependent manner. In addition, high glucose increased BACE1 and APP-C99 expressions, which were reversed by a reactive oxygen species (ROS) scavenger. Indeed, high glucose increased intracellular ROS levels and HIF-1α expression, associated with regulation of BACE1 and Liver X Receptor α (LXRα). In addition, high glucose induced ATP-binding cassette transporter A1 (ABCA1) down-regulation, was associated with LXR-induced lipid raft reorganization and BACE1 localization on the lipid raft. Furthermore, silencing of BACE1 expression was shown to regulate Aβ secretion and apoptosis of SK-N-MC. In conclusion, high glucose upregulates BACE1 expression and activity through HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization, leading to Aβ production and apoptosis of SK-N-MC. PMID:27829662

Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide.

PubMed

Ikenoue, T; Okazaki, K; Fujitani, S; Tsuchiya, Y; Akiyoshi, M; Maki, T; Kondo, N

1997-04-01

(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new nonsulfonylurea hypoglycemic agent that lowers blood glucose by stimulating insulin release. In the present study, we examined the effects of A-4166, voglibose (an alpha-glucosidase inhibitor), and glibenclamide (a sulfonylurea) on the postprandial glycemic increase in rats with or without diabetes mellitus. Oral administration of A-4166 (25-100 mg/kg) dose-dependently decreased blood glucose with a rapid onset and short duration in normal rats. On the other hand, glibenclamide (1-4 mg/kg) showed a slower onset of its hypoglycemic action, and voglibose (0.2 mg/kg) had no effect. In the case of postprandial glucose excursion, the carbohydrate-induced increase in blood glucose was reduced by oral administration of either A-4166 or voglibose without causing sustained hypoglycemia in both normal and neonatal streptozotocin-induced diabetic rats. However, the efficacy of voglibose varied with the type of carbohydrate load. Glibenclamide produced a prolonged decrease in blood glucose without any appreciable effect on the initial glucose excursion. After sucrose loading, plasma insulin levels during the initial 1 h were significantly higher in A-4166-treated rats than in control rats, while voglibose completely inhibited the insulin response to sucrose. In glibenclamide-treated rats, an augmented insulin response was not seen. In conclusion, unlike other hypoglycemic agents, A-4166 suppresses postprandial glucose excursions by stimulating the early phase of insulin secretion.

Cinnamon water extracts increase glucose uptake but inhibit adiponectin secretion in 3T3-L1 adipose cells.

PubMed

Roffey, Benjamin; Atwal, Avtar; Kubow, Stan

2006-08-01

The effects of three concentrations (0.2, 0.3, and 0.4 mg/mL) of a cinnamon extract (CE) (Cinnamomum zeylanicum) on glucose uptake and adiponectin secretion in 3T3-L1 adipocytes were examined in the presence and absence of 0.5 nM and 50 nM insulin. In the absence of insulin, adipocytes exposed to 0.2 mg/mL CE showed an approximate two-fold increase in glucose uptake relative to controls although glucose uptake was unaffected by the two higher concentrations of CE. No effect of CE on glucose uptake was noted in the presence of 0.5 nM insulin whereas the two highest concentrations (0.3 and 0.4 mg/mL) of CE showed a significant dose-dependent decrease in glucose uptake in the presence of 50 nM insulin. Treatment of the adipocytes with 50 nM wortmannin, an irreversible inhibitor of the p110 isoform of phosphoinositide 3'-kinase, was associated with complete inhibition of the stimulated glucose uptake induced by 0.2 mg/mL CE. Treatment of the adipocytes with 0.2 mg/mL CE was associated with an inhibition of adiponectin secretion to levels that were nondetectable. The present study indicates that although 0.2 mg/mL CE has insulin-mimetic action in 3T3-adipocytes in terms of glucose uptake, secretion of the antidiabetic hormone adiponectin is adversely affected.

Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling.

PubMed

Shen, Yan; Honma, Natsumi; Kobayashi, Katsuya; Jia, Liu Nan; Hosono, Takashi; Shindo, Kazutoshi; Ariga, Toyohiko; Seki, Taiichiro

2014-01-01

We previously demonstrated that cinnamon extract (CE) ameliorates type 1 diabetes induced by streptozotocin in rats through the up-regulation of glucose transporter 4 (GLUT4) translocation in both muscle and adipose tissues. This present study was aimed at clarifying the detailed mechanism(s) with which CE increases the glucose uptake in vivo and in cell culture systems using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Specific inhibitors of key enzymes in insulin signaling and AMP-activated protein kinase (AMPK) signaling pathways, as well as small interference RNA, were used to examine the role of these kinases in the CE-induced glucose uptake. The results showed that CE stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase. An AMPK inhibitor and LKB1 siRNA blocked the CE-induced glucose uptake. We also found for the first time that insulin suppressed AMPK activation in the adipocyte. To investigate the effect of CE on type 2 diabetes in vivo, we further performed oral glucose tolerance tests and insulin tolerance tests in type 2 diabetes model rats administered with CE. The CE improved glucose tolerance in oral glucose tolerance tests, but not insulin sensitivity in insulin tolerance test. In summary, these results indicate that CE ameliorates type 2 diabetes by inducing GLUT4 translocation via the AMPK signaling pathway. We also found insulin antagonistically regulates the activation of AMPK.

Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells.

PubMed

Tsukahara, Tamotsu; Haniu, Hisao; Matsuda, Yoshikazu

2013-04-12

Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA-PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance. Copyright © 2013 Elsevier Inc. All rights reserved.

The effects of long term fasting in Ramadan on glucose regulation in type 2 diabetes mellitus.

PubMed

Karatoprak, C; Yolbas, S; Cakirca, M; Cinar, A; Zorlu, M; Kiskac, M; Cikrikcioglu, M A; Erkoc, R; Tasan, E

2013-09-01

For Ramadan fasting, observing Muslims do not eat or drink between sunrise and sunset during Ramadan, Islam's holy month of the year according to the lunar calendar. In 2011, fasting patients with diabetes fasted for an average of 16.5 hours per day, having 2 meals between sunset and sunrise for a month. We aimed to evaluate the impact of extended fasting on glucose regulation and observe possible complications of extended fasting in type 2 diabetes mellitus patients. We conducted a randomized, retrospective, observational study. Patients who presented at the Diabetes Clinic during the 15 days before and after Ramadan in August 2011 Istanbul, whose hemoglobin A1c, fasting plasma glucose, postprandial plasma glucose, weight and height value examinations and follow-up were completed were included in the study. Seventy-six diabetes patients who fasted during Ramadan (fasting group) and 71 patients with diabetes who did not fast (non-fasting group) were included in the study. These two groups with similar demographic characteristics were compared before and after Ramadan. HbA1c, fasting and postprandial plasma glucose, body mass index, weight and adverse events were evaluated. No statistically significant difference was observed among the fasting and the non-fasting groups. There was no difference between the pre and post-Ramadan values of the fasting group. We could not find any negative effects of extended fasting on glucose regulation of patients with diabetes who are using certain medications. No serious adverse event was observed. We failed to demonstrate benefits of increasing the number of meals in patients with diabetes.

Clinical validation of a new control-oriented model of insulin and glucose dynamics in subjects with type 1 diabetes.

PubMed

Fabietti, Pier Giorgio; Canonico, Valentina; Orsini-Federici, Marco; Sarti, Eugenio; Massi-Benedetti, Massimo

2007-08-01

The development of an artificial pancreas requires an accurate representation of diabetes pathophysiology to create effective and safe control systems for automatic insulin infusion regulation. The aim of the present study is the assessment of a previously developed mathematical model of insulin and glucose metabolism in type 1 diabetes and the evaluation of its effectiveness for the development and testing of control algorithms. Based on the already existing "minimal model" a new mathematical model was developed composed of glucose and insulin submodels. The glucose model includes the representation of peripheral uptake, hepatic uptake and release, and renal clearance. The insulin model describes the kinetics of exogenous insulin injected either subcutaneously or intravenously. The estimation of insulin sensitivity allows the model to personalize parameters to each subject. Data sets from two different clinical trials were used here for model validation through simulation studies. The first set had subcutaneous insulin injection, while the second set had intravenous insulin injection. The root mean square error between simulated and real blood glucose profiles (G(rms)) and the Clarke error grid analysis were used to evaluate the system efficacy. Results from our study demonstrated the model's capability in identifying individual characteristics even under different experimental conditions. This was reflected by an effective simulation as indicated by G(rms), and clinical acceptability by the Clarke error grid analysis, in both clinical data series. Simulation results confirmed the capacity of the model to faithfully represent the glucose-insulin relationship in type 1 diabetes in different circumstances.

A novel model for studies of blood-mediated long-term responses to cellular transplants

PubMed Central

Lindblom, Susanne; Hong, Jaan; Nilsson, Bo; Korsgren, Olle; Ronquist, Gunnar

2015-01-01

Aims Interaction between blood and bio-surfaces is important in many medical fields. With the aim of studying blood-mediated reactions to cellular transplants, we developed a whole-blood model for incubation of small volumes for up to 48 h. Methods Heparinized polyvinyl chloride tubing was cut in suitable lengths and sealed to create small bags. Multiple bags, with fresh venous blood, were incubated attached to a rotating wheel at 37°C. Physiological variables in blood were monitored: glucose, blood gases, mono- and divalent cations and chloride ions, osmolality, coagulation (platelet consumption, thrombin-antithrombin complexes (TAT)), and complement activation (C3a and SC5b-9), haemolysis, and leukocyte viability. Results Basic glucose consumption was high. Glucose depletion resulted in successive elevation of extracellular potassium, while sodium and calcium ions decreased due to inhibition of energy-requiring ion pumps. Addition of glucose improved ion balance but led to metabolic acidosis. To maintain a balanced physiological environment beyond 6 h, glucose and sodium hydrogen carbonate were added regularly based on analyses of glucose, pH, ions, and osmotic pressure. With these additives haemolysis was prevented for up to 72 h and leukocyte viability better preserved. Despite using non-heparinized blood, coagulation and complement activation were lower during long-term incubations compared with addition of thromboplastin and collagen. Conclusion A novel whole-blood model for studies of blood-mediated responses to a cellular transplant is presented allowing extended observations for up to 48 h and highlights the importance of stringent evaluations and adjustment of physiological conditions. PMID:25322825

Facile synthesis of a silver nanoparticles/polypyrrole nanocomposite for non-enzymatic glucose determination.

PubMed

Poletti Papi, Maurício A; Caetano, Fabio R; Bergamini, Márcio F; Marcolino-Junior, Luiz H

2017-06-01

The present work describes the synthesis of a new conductive nanocomposite based on polypyrrole (PPy) and silver nanoparticles (PPy-AgNP) based on a facile reverse microemulsion method and its application as a non-enzymatic electrochemical sensor for glucose detection. Focusing on the best sensor performance, all experimental parameters used in the synthesis of nanocomposite were optimized based on its electrochemical response for glucose. Characterization of the optimized material by FT-IR, cyclic voltammetry, and DRX measurements and TEM images showed good monodispersion of semispherical Ag nanoparticles capped by PPy structure, with size average of 12±5nm. Under the best analytical conditions, the proposed sensor exhibited glucose response in linear dynamic range of 25 to 2500μmolL -1 , with limit of detection of 3.6μmolL -1 . Recovery studies with human saliva samples varying from 99 to 105% revealed the accuracy and feasibility of a non-enzymatic electrochemical sensor for glucose determination by easy construction and low-cost. Copyright © 2017 Elsevier B.V. All rights reserved.

Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

NASA Astrophysics Data System (ADS)

Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A.; Ghosh, Partha Pratim; Mitra, Prasenjit

2016-06-01

Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.

"Structure-size me:" weight and health changes in a four week residential program.

PubMed

Shapiro, Jennifer R; Stout, Anna L; Musante, Gerard J

2006-08-01

The prevalence of obesity has been drastically increasing over the past 20 years. Other obesity related conditions, including type 2 diabetes mellitus, have also increased in a corresponding manner and, in 2005, the American Diabetes Association (ADA) reduced the cut-off for defining impaired blood glucose. Evidence suggests that just a modest amount of weight loss can improve obesity related co-morbidities. The present study first, investigated changes in health measures after participation in a four week residential weight loss program. Second, individuals were classified according to the 2005 criteria for the diagnosis of type 2 diabetes to determine if glucose regulation changed after weight loss. A total of 93 individuals were categorized as normal glucose (n=56), impaired fasting glucose (n=23) or diabetic range (n=14) after initial blood laboratory screening. After four weeks and a 6.5% weight reduction, participants showed significant improvements in health risks. Further, most participants with elevated fasting glucose shifted into a healthier range. Findings are discussed in terms of health improvements that occur after weight loss within a four week lifestyle intervention.

Histone 2A stimulates glucose-6-phosphatase activity by permeabilization of liver microsomes.

PubMed

Benedetti, Angelo; Fulceri, Rosella; Allan, Bernard B; Houston, Pamela; Sukhodub, Andrey L; Marcolongo, Paola; Ethell, Brian; Burchell, Brian; Burchell, Ann

2002-10-15

Histone 2A increases glucose-6-phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal glucose-6-phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on glucose-6-phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates glucose-6-phosphatase activity by permeabilizing the microsomal membrane.

Histone 2A stimulates glucose-6-phosphatase activity by permeabilization of liver microsomes.

PubMed Central

Benedetti, Angelo; Fulceri, Rosella; Allan, Bernard B; Houston, Pamela; Sukhodub, Andrey L; Marcolongo, Paola; Ethell, Brian; Burchell, Brian; Burchell, Ann

2002-01-01

Histone 2A increases glucose-6-phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal glucose-6-phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on glucose-6-phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates glucose-6-phosphatase activity by permeabilizing the microsomal membrane. PMID:12097138

A comparison between the impact of two types of dietary protein on brain glucose concentrations and oxidative stress in high fructose-induced metabolic syndrome rats.

PubMed

Madani, Zohra; Malaisse, Willy J; Ait-Yahia, Dalila

2015-09-01

The present study explored the potential of fish proteins to counteract high glucose levels and oxidative stress induced by fructose in the brain. A total of 24 male Wistar rats consumed sardine protein or casein with or without high fructose (64%). After 2 months, brain tissue was used for analyses. The fructose rats exhibited an increase in body mass index (BMI), body weight, absolute and relative brain weights and brain glucose; however, there was a decrease in food and water intake. Fructose disrupts membrane homeostasis, as evidenced by an increase in the brain hydroperoxides and a decrease in catalase (CAT) and glutathione peroxidase (GSH-Px) compared to the control. The exposure to the sardine protein reduced BMI, food intake, glucose and hydroperoxides, and increased CAT and GSH-Px in the brain. In conclusion, the metabolic dysfunctions associated with the fructose treatment were ameliorated by the presence of sardine protein in the diet by decreasing BMI, brain glucose and lipid peroxidation, and increasing CAT and GSH-Px activities.

Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

PubMed Central

Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A; Ghosh, Partha Pratim; Mitra, Prasenjit

2016-01-01

Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID:27282931

A Bayesian network for modelling blood glucose concentration and exercise in type 1 diabetes.

PubMed

Ewings, Sean M; Sahu, Sujit K; Valletta, John J; Byrne, Christopher D; Chipperfield, Andrew J

2015-06-01

This article presents a new statistical approach to analysing the effects of everyday physical activity on blood glucose concentration in people with type 1 diabetes. A physiologically based model of blood glucose dynamics is developed to cope with frequently sampled data on food, insulin and habitual physical activity; the model is then converted to a Bayesian network to account for measurement error and variability in the physiological processes. A simulation study is conducted to determine the feasibility of using Markov chain Monte Carlo methods for simultaneous estimation of all model parameters and prediction of blood glucose concentration. Although there are problems with parameter identification in a minority of cases, most parameters can be estimated without bias. Predictive performance is unaffected by parameter misspecification and is insensitive to misleading prior distributions. This article highlights important practical and theoretical issues not previously addressed in the quest for an artificial pancreas as treatment for type 1 diabetes. The proposed methods represent a new paradigm for analysis of deterministic mathematical models of blood glucose concentration. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effects of telephone follow-up on blood glucose levels and postpartum screening in mothers with Gestational Diabetes Mellitus.

PubMed

Khorshidi Roozbahani, Rezvan; Geranmayeh, Mehrnaz; Hantoushzadeh, Sedigheh; Mehran, Abbas

2015-01-01

Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. GDM, defined as glucose intolerance, first diagnosed or initiated during pregnancy affects 1-14% of pregnancies based on various studies. Screening and early diagnosis and appropriate glycemic control can improve prenatal outcomes. Telephone follow-up seems to be a reasonable way for pregnant women follow-up. The present study evaluated the effects of telephone follow-up on blood glucose level during pregnancy and postpartum screening. Eighty mothers with GDM were enrolled in this clinical trial and randomly divided into intervention and control groups. All mothers were asked to check their blood sugar levels fivetimes daily. In intervention group, telephone intervention was performed for 10 weeks. In each follow-up, individuals were followed for insulin injections, diet, clinical tests and reminding the next visit. In control group, three times of telephone call was established to record blood sugar levels. Another telephone call was established at 6 weeks of postpartum in both study groups to evaluate the performance of the screening test for blood sugar. The mean age of mothers was 30.9±5 years in the control and 30.7±5.1 years in the intervention groups In intervention group, mean level of blood glucose, 2 hours after lunch at 28 weeks of pregnancy was significantly lower than the control group (P<0.05). Mean differences in levels of fasting blood glucose between 28 weeks and 32 and between 28 and 36 weeks of pregnancy were significantly higher in the intervention than the control group (P<0.05). Rate of postpartum glucose screening test was significantly higher in the intervention group (P<0.001). The findings of this study demonstrated that telephone follow-up could significantly reduce fasting blood glucose levels in mothers with gestational diabetes and also increased the rate of postpartum screening test.

Design and clinical pilot testing of the model-based dynamic insulin sensitivity and secretion test (DISST).

PubMed

Lotz, Thomas F; Chase, J Geoffrey; McAuley, Kirsten A; Shaw, Geoffrey M; Docherty, Paul D; Berkeley, Juliet E; Williams, Sheila M; Hann, Christopher E; Mann, Jim I

2010-11-01

Insulin resistance is a significant risk factor in the pathogenesis of type 2 diabetes. This article presents pilot study results of the dynamic insulin sensitivity and secretion test (DISST), a high-resolution, low-intensity test to diagnose insulin sensitivity (IS) and characterize pancreatic insulin secretion in response to a (small) glucose challenge. This pilot study examines the effect of glucose and insulin dose on the DISST, and tests its repeatability. DISST tests were performed on 16 subjects randomly allocated to low (5 g glucose, 0.5 U insulin), medium (10 g glucose, 1 U insulin) and high dose (20 g glucose, 2 U insulin) protocols. Two or three tests were performed on each subject a few days apart. Average variability in IS between low and medium dose was 10.3% (p=.50) and between medium and high dose 6.0% (p=.87). Geometric mean variability between tests was 6.0% (multiplicative standard deviation (MSD) 4.9%). Geometric mean variability in first phase endogenous insulin response was 6.8% (MSD 2.2%). Results were most consistent in subjects with low IS. These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS. © 2010 Diabetes Technology Society.

Phytochemical screening, physicochemical properties, acute toxicity testing and screening of hypoglycaemic activity of extracts of Eremurus himalaicus baker in normoglycaemic Wistar strain albino rats.

PubMed

Mushtaq, Ahlam; Akbar, Seema; Zargar, Mohammad A; Wali, Adil F; Malik, Akhtar H; Dar, Mohammad Y; Hamid, Rabia; Ganai, Bashir A

2014-01-01

In the present study EtOAc, MeOH, and aqueous extracts of Eremurus himalaicus were evaluated for hypoglycaemic effect in normal rats using both oral glucose tolerance test and 14-day oral administration study. Phytochemical and physicochemical screening was also done. In oral glucose tolerance test the aqueous and MeOH extracts of Eremurus himalaicus at a dose level of 500 mg/kg body weight prior to glucose load resulted in a significant fall in blood glucose level within 150 min. of glucose administration. The aqueous extract at a dose level of 250 mg/kg body weight and 500 mg/kg body weight also showed good hypoglycaemic response (P < 0.001); this was followed by MeOH extract at a dose level of 500 mg/kg body weight (P < 0.05), while MeOH extract at dose level of 250 mg/kg body weight and ethyl acetate extract at dose level of 250 mg/kg body weight and 500 mg/kg body weight exhibited insignificant effect. Phytochemical screening of extracts revealed the presence of alkaloids, terpenoids, phenolics, tannins, saponins, cardiac glycosides, and flavonoids. The results indicate that aqueous extract possess significant hypoglycaemic activity in normoglycaemic rats which may be attributed to the above-mentioned chemical constituents.

Efficacy of herbal toothpastes on salivary pH and salivary glucose - A preliminary study.

PubMed

Khairnar, Mahesh R; Dodamani, Arun S; Karibasappa, G N; Naik, Rahul G; Deshmukh, Manjiri A

Due to dearth of literature on the effect of herbal toothpaste on saliva and salivary constituents, the present study was undertaken to evaluate and compare the effect of three different herbal toothpastes with the focus on on salivary pH and salivary glucose. Forty five subjects in the age group of 19-21 years were randomly divided into 3 groups (15 in each group) and were randomly intervened with three different herbal toothpastes (Dant Kanti, Himalaya Complete Care and Vicco Vajradanti). Unstimulated saliva samples were collected before and after brushing and salivary glucose and pH levels were assessed at an interval of one week each for a period of 4 weeks starting from day 1. All the three toothpastes were effective in reducing the overall (p < 0.05) levels as well as levels of salivary glucose from pre-brushing to post-brushing at each interval (p < 0.05) and in increasing the overall levels as well as levels of salivary pH (p < 0.05) from pre-brushing to post-brushing at each interval. Herbal toothpastes were effective in reducing salivary levels of glucose and improving pH of the saliva. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Effect of Static Compressive Strain, Anisotropy, and Tissue Region on the Diffusion of Glucose in Meniscus Fibrocartilage.

PubMed

Kleinhans, Kelsey L; Jaworski, Lukas M; Schneiderbauer, Michaela M; Jackson, Alicia R

2015-10-01

Osteoarthritis (OA) is a significant socio-economic concern, affecting millions of individuals each year. Degeneration of the meniscus of the knee is often associated with OA, yet the relationship between the two is not well understood. As a nearly avascular tissue, the meniscus must rely on diffusive transport for nutritional supply to cells. Therefore, quantifying structure-function relations for transport properties in meniscus fibrocartilage is an important task. The purpose of the present study was to determine how mechanical loading, tissue anisotropy, and tissue region affect glucose diffusion in meniscus fibrocartilage. A one-dimensional (1D) diffusion experiment was used to measure the diffusion coefficient of glucose in porcine meniscus tissues. Results show that glucose diffusion is strain-dependent, decreasing significantly with increased levels of compression. It was also determined that glucose diffusion in meniscus tissues is anisotropic, with the diffusion coefficient in the circumferential direction being significantly higher than that in the axial direction. Finally, the effect of tissue region was not statistically significant, comparing axial diffusion in the central and horn regions of the tissue. This study is important for better understanding the transport and nutrition-related mechanisms of meniscal degeneration and related OA in the knee.

Oxygen-Glucose Deprivation (OGD) Modulates the Unfolded Protein Response (UPR) and Inflicts Autophagy in a PC12 Hypoxia Cell Line Model.

PubMed

Vavilis, Theofanis; Delivanoglou, Nikoleta; Aggelidou, Eleni; Stamoula, Eleni; Mellidis, Kyriakos; Kaidoglou, Aikaterini; Cheva, Angeliki; Pourzitaki, Chryssa; Chatzimeletiou, Katerina; Lazou, Antigone; Albani, Maria; Kritis, Aristeidis

2016-07-01

Hypoxia is the lack of sufficient oxygenation of tissue, imposing severe stress upon cells. It is a major feature of many pathological conditions such as stroke, traumatic brain injury, cerebral hemorrhage, perinatal asphyxia and can lead to cell death due to energy depletion and increased free radical generation. The present study investigates the effect of hypoxia on the unfolded protein response of the cell (UPR), utilizing a 16-h oxygen-glucose deprivation protocol (OGD) in a PC12 cell line model. Expression of glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94), key players of the UPR, was studied along with the expression of glucose-regulated protein 75 (GRP75), heat shock cognate 70 (HSC70), and glyceraldehyde 3-phosphate dehydrogenase, all with respect to the cell death mechanism(s). Cells subjected to OGD displayed upregulation of GRP78 and GRP94 and concurrent downregulation of GRP75. These findings were accompanied with minimal apoptotic cell death and induction of autophagy. The above observation warrants further investigation to elucidate whether autophagy acts as a pro-survival mechanism that upon severe and prolonged hypoxia acts as a concerted cell response leading to cell death. In our OGD model, hypoxia modulates UPR and induces autophagy.

Short-term effect of add on bell pepper (Capsicum annuum var. grossum) juice with integrated approach of yoga therapy on blood glucose levels and cardiovascular functions in patients with type 2 diabetes mellitus: A randomized controlled study.

PubMed

Nagasukeerthi, Padakandla; Mooventhan, A; Manjunath, N K

2017-10-01

Type 2 diabetes mellitus (T2DM) is a major global health problem. Though various studies have reported the beneficial effect of Yoga in patient with T2DM, there is a lack of study in combination with bell pepper and yoga. Hence, the present study aims at evaluating short-term effect of add on bell pepper juice with integrated approach of yoga therapy (IAYT) on blood glucose levels and cardiovascular variables in patients with T2DM. Fifty T2DM subjects with the age varied from 34 to 69-years were recruited and randomly divided into either study group or control group. The study group received 100-ml of bell pepper juice (twice/day) along with IAYT while the control group received only IAYT for 4-consecutive days. Baseline and post-test assessments were taken before and after the intervention. Statistical analysis was performed using statistical package for the social sciences, version-16. Results of this study showed no significant difference in overall (fasting and post prandial) blood glucose level in the study group compared with control group. However, a significant reduction in Post prandial blood glucose (PPBG), systolic blood pressure (SBP), pulse pressure (PP), rate pressure product (RPP) and Double product (Do-P) was observed in the study group compared with control group. Results of this study suggest that though an addition of 100-ml of bell pepper juice (twice/day) along with IAYT is not more effective in reducing fasting blood glucose, it may be more effective in reducing PPBG, SBP, PP, RPP and Do-P than IAYT alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glucose-Induced Acidification in Yeast Cultures

ERIC Educational Resources Information Center

Myers, Alan; Bourn, Julia; Pool, Brynne

2005-01-01

We present an investigation (for A-level biology students and equivalent) into the mechanism of glucose-induced extracellular acidification in unbuffered yeast suspensions. The investigation is designed to enhance understanding of aspects of the A-level curriculum that relate to the phenomenon (notably glucose catabolism) and to develop key skills…

Response to deep hypoglycemia does not involve glucoreceptors in carotid perfused tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cane, P.; Haun, C.K.; Evered, J.

1988-11-01

In the present study the authors examined whether the magnified hormonal counter-regulatory response seen during deep hypoglycemia (40 mg/dl) could be attenuated by supplying the forebrain with glucose furnished through carotid infusion. Two protocols were performed in conscious dogs. In the first protocol they infused glucose bilaterally into the carotid circulation to produce a forebrain glycemia of 55 {plus minus} 1 mg/dl whereas systemic glycemia declined to 39 {plus minus} 2 mg/dl. In the second protocol as a control they infused glucose into the systemic circulation at a rate matched to protocol 1 so that both systemic and jugular plasmamore » glucose concentrations were equivalent to the systemic glucose concentrations in protocol 1. In spite of a substantial difference in forebrain glycemia there were no differences in the counter-regulatory responses of catecholamines or glucagon. In addition, through the use of radiolabeled microspheres, they defined the precise regions of the forebrain irrigated during bilateral intracarotid glucose infusions. The concentration of microspheres was high in the forebrain but very low in the hindbrain. The results indicate that glucoreceptor cells in tissues perfused by carotid arteries may play a tautological role in the sympathetic response to hypoglycemia and imply that glucose-sensitive receptors must also be located elsewhere in the central nervous system or in the periphery.« less

Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake cycle.

PubMed

Netchiporouk, L; Shram, N; Salvert, D; Cespuglio, R

2001-04-01

In the present study, cortical extracellular levels of glucose were monitored for the first time throughout the sleep-wake states of the freely moving rat. For this purpose, polygraphic recordings (electroencephalogram of the fronto-occipital cortices and electromyogram of the neck muscles) were achieved in combination with differential normal pulse voltammetry (DNPV) using a specific glucose sensor. Data obtained reveal that the basal extracellular glucose concentration in the conscious rat is 0.59 +/- 0.3 m M while under chloral hydrate anaesthesia (0.4 g/kg, i.p.) it increases up to 180% of its basal concentration. Regarding the sleep-wake cycle, the existence of spontaneous significant variations in the mean glucose level during slow-wave sleep (SWS = +13%) and paradoxical sleep (PS = -11%) compared with the waking state (100%) is also reported. It is to be noticed that during long periods of active waking, glucose level tends towards a decrease that becomes significant after 15 min (active waking = -32%). On the contrary, during long episodes of slow-wave sleep, it tends towards an increase which becomes significant after 12 min (SWS = +28%). It is suggested that voltammetric techniques using enzymatic biosensors are useful tools allowing direct glucose measurements in the freely moving animal. On the whole, paradoxical sleep is pointed out as a state highly dependent on the availability of energy and slow-wave sleep as a period of energy saving.

Oral Lactobacillus reuteri GMN-32 treatment reduces blood glucose concentrations and promotes cardiac function in rats with streptozotocin-induced diabetes mellitus.

PubMed

Lin, Chih-Hsueh; Lin, Cheng-Chieh; Shibu, Marthandam Asokan; Liu, Chiu-Shong; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Hsieh, Cheng-Hong; Chen, Yi-Hsing; Huang, Chih-Yang

2014-02-01

Impaired regulation of blood glucose levels in diabetes mellitus (DM) patients and the associated elevation of blood glucose levels are known to increase the risk of diabetic cardiomyopathy (DC). In the present study, a probiotic bacterium, Lactobacillus reuteri GMN-32, was evaluated for its potential to reduce blood glucose levels and to provide protection against DC risks in streptozotocin (STZ)-induced DM rats. The blood glucose levels of the STZ-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l (with 10⁷ colony-forming units (cfu)/d) and 3040 mg/l (with 10⁹ cfu/d). Probiotic treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. The results highlight that L. reuteri GMN-32 treatment reduces blood glucose levels, inhibits caspase 8-mediated apoptosis and promotes cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats.

Effects of fluid, electrolyte and substrate ingestion on endurance capacity.

PubMed

Maughan, R J; Fenn, C E; Leiper, J B

1989-01-01

The availability of carbohydrate (CHO) as a substrate for the exercising muscles is known to be a limiting factor in the performance of prolonged cycle exercise, and provision of exogenous CHO in the form of glucose can increase endurance capacity. The present study examined the effects of ingestion of fluids and of CHO in different forms on exercise performance. Six male volunteers exercised to exhaustion on a cycle ergometer at a workload which required approximately 70% of Vo2max. After one preliminary trial, subjects performed this exercise test on six occasions, one week apart. Immediately before exercise, and at 10-min intervals throughout, subjects ingested 100 ml of one of the following: control (no drink), water, glucose syrup, fructose syrup, glucose-fructose syrup or a dilute glucose-electrolyte solution. Each of the syrup solutions contained approximately 36 g CHO per 100 ml; the isotonic glucose-electrolyte solution contained 4 g glucose per 100 ml. A randomised Latin square order of administration of trials was employed. Expired air samples for determination of Vo2, respiratory exchange ratio and rate of CHO oxidation were collected at 15-min intervals. Venous blood samples were obtained before and after exercise. Subjects drinking the isotonic glucose-electrolyte solution exercised longer (90.8 (12.4) min, mean (SEM] than on the control test (70.2 (8.3) min; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Apigenin and naringenin ameliorate PKCβII-associated endothelial dysfunction via regulating ROS/caspase-3 and NO pathway in endothelial cells exposed to high glucose.

PubMed

Qin, Weiwei; Ren, Bei; Wang, Shanshan; Liang, Shujun; He, Baiqiu; Shi, Xiaoji; Wang, Liying; Liang, Jingyu; Wu, Feihua

2016-10-01

Endothelial dysfunction is a key event in the progression of atherosclerosis with diabetes. Increasing cell apoptosis may lead to endothelial dysfunction. Apigenin and naringenin are two kinds of widely used flavones. In the present study, we investigated whether and how apigenin and naringenin reduced endothelial dysfunction induced by high glucose in endothelial cells. We showed that apigenin and naringenin protected against endothelial dysfunction via inhibiting phosphorylation of protein kinase C βII (PKCβII) expression and downstream reactive oxygen species (ROS) production in endothelial cells exposed to high glucose. Furthermore, we demonstrated that apigenin and naringenin reduced high glucose-increased apoptosis, Bax expression, caspase-3 activity and phosphorylation of NF-κB in endothelial cells. Moreover, apigenin and naringenin effectively restored high glucose-reduced Bcl-2 expression and Akt phosphorylation. Importantly, apigenin and naringenin significantly increased NO production in endothelial cells subjected to high glucose challenge. Consistently, high glucose stimulation impaired acetylcholine (ACh)-mediated vasodilation in the rat aorta, apigenin and naringenin treatment restored the impaired endothelium-dependent vasodilation via dramatically increasing eNOS activity and nitric oxide (NO) level. Taken together, our results manifest that apigenin and naringenin can ameliorate endothelial dysfunction via regulating ROS/caspase-3 and NO pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes.

PubMed

Ohta, Mitsuhiro; Fujinami, Aya; Kobayashi, Norihiro; Amano, Akiko; Ishigami, Akihito; Tokuda, Harukuni; Suzuki, Nobutaka; Ito, Fumitake; Mori, Taisuke; Sawada, Morio; Iwasa, Koichi; Kitawaki, Jo; Ohnishi, Katsunori; Tsujikawa, Muneo; Obayashi, Hiroshi

2015-07-01

4-Hydroxyderricin (4HD) and xanthoangelol (XAG) are major components of n-hexane/ethyl acetate (5:1) extract of the yellow-colored stem juice of Angelica keiskei. 4-Hydroxyderricin and XAG have been reported to increase glucose transporter 4 (GLUT4)-dependent glucose uptake in 3T3-L1 adipocytes, but the detailed mechanism of this phenomenon remains unknown. This present study was aimed at clarifying the detailed mechanism by which 4HD and XAG increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes. Both 4HD and XAG increased glucose uptake and GLUT4 translocation to the plasma membrane. 4-Hydroxyderricin and XAG also stimulated the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase. In addition, phosphorylation of liver kinase B1 (LKB1), which acts upstream of AMPK, was also increased by 4HD and XAG treatment. Small interfering RNA knockdown of LKB1 attenuated 4HD- and XAG-stimulated AMPK phosphorylation and suppressed glucose uptake. These findings demonstrate that 4HD and XAG can increase GLUT4-dependent glucose uptake through the LKB1/AMPK signaling pathway in 3T3-L1 adipocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of GSH with exogenous agents leads to changes in glyoxalase 1 enzyme activity in VL-17A cells exposed to chronic alcohol plus high glucose.

PubMed

Kumar, S Mathan; Swaminathan, Kavitha; Clemens, Dahn L; Dey, Aparajita

2014-02-01

Gluthathione (GSH) is a major cellular antioxidant. The present study utilizing VL-17A cells exposed to chronic alcohol plus high glucose investigated the changes in oxidative stress, toxicity, and glyoxalase 1 activity as a detoxification pathway due to changes in GSH level through GSH supplementation with N-acetyl cysteine (NAC) or ursodeoxycholic acid (UDCA) and its depletion through buthionine sulfoximine (BSO) or diethyl maleate (DEM). Glyoxalase 1 plays an important role in detoxification of methylglyoxal which is formed as a precursor of advanced glycated end products formed due to high glucose mediated oxidative stress. Significant changes in glyoxalase 1 activity utilizing methylglyoxal or glyoxal as substrates occurred with NAC or UDCA or BSO or DEM supplementation in chronic alcohol plus high glucose treated VL-17A cells. NAC or UDCA administration in chronic alcohol plus high glucose treated VL-17A cells increased viability and decreased ROS levels, lipid peroxidation and 3-nitrotyrosine adduct formation. Similarly, GSH depletion with BSO or DEM had an opposite effect on the parameters in chronic alcohol plus high glucose treated VL-17A cells. In conclusion, modulation of GSH with NAC or UDCA or BSO or DEM leads to significant changes in oxidative stress, glyoxalase 1 enzyme activity and toxicity in chronic alcohol plus high glucose treated VL-17A cells.

Insulin resistance possible risk factor for cognitive impairment in fibromialgic patients.

PubMed

Fava, Antonietta; Plastino, Massimiliano; Cristiano, Dario; Spanò, Antonio; Cristofaro, Stefano; Opipari, Carlo; Chillà, Antonio; Casalinuovo, Fatima; Colica, Carmen; De Bartolo, Matteo; Pirritano, Domenico; Bosco, Domenico

2013-12-01

To evaluate glucose metabolism and/or insulin resistance (IR) in 96 patients with Fibromyalgia (FM), associated or not to cognitive impairment. We investigated glucose metabolism in 96 FM patients. Enrolled patients were divided into two groups: 48 patients with memory deficit (group A) and 48 without memory deficit (control group). We evaluated glucose and insulin levels after a 2 h-Oral-Glucose-Tolerance-Test (2 h-OGTT) and insulin resistance (IR) by the homeostasis model assessment formula (HOMA). Body Mass Index (BMI), waist-to-hip-ratio (WHR), anxiety level, fasting plasma insulin and Non-Steroidal Anti-Inflammatory agents use were higher in patients with FM with memory impairment; while age, sex, waist circumference, education level, fasting plasma glucose, glycate hemoglobin, triglycerides, blood lipid profile, C- Reactivity-Protein (CRP), blood pressure and smoking habits were similar in both groups. Following OGTT the prevalence of glucose metabolism abnormalities was significantly higher in group A. IR was present in 79% patients, of whom 23% had also impaired glucose tolerance, 4% newly diagnosed diabetes mellitus and 52% IR only. Obesity and overweight prevailed in group A. IR, but not BMI or WHR was associated to an increased risk of memory impairment (OR = 2,6; 95% CI: 1,22-3,7). The results of this study suggest that IR may represent a risk factor for memory impairment in fibromialgic patients.