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Sample records for 1-h plasma glucose

  1. Predictability of 1-h postload plasma glucose concentration: A 10-year retrospective cohort study

    PubMed Central

    Kuang, Lifen; Huang, Zhimin; Hong, Zhenzhen; Chen, Ailing; Li, Yanbing

    2015-01-01

    Aims/Introduction Elevated 1-h postload plasma glucose concentration (1hPG) during oral glucose tolerance test has been linked to an increased risk of type 2 diabetes and a poorer cardiometabolic risk profile. The present study analyzed the predictability and cut-off point of 1hPG in predicting type 2 diabetes in normal glucose regulation (NGR) subjects, and evaluated the long-term prognosis of NGR subjects with elevated 1hPG in glucose metabolism, kidney function, metabolic states and atherosclerosis. Materials and Methods A total of 116 Han Chinese classified as NGR in 2002 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, were investigated. Follow-up was carried out in 2012 to evaluate the progression of glucose metabolism, kidney function, metabolic syndrome and carotid atherosclerosis. Results The areas under receiver operating characteristic curves were higher for 1hPG than FPG or 2hPG (0.858 vs 0.806 vs 0.746). The cut-off value of 1hPG with the maximal sum of sensitivity and specificity in predicting type 2 diabetes in NGR subjects was 8.85 mmol/L. The accumulative incidence of type 2 diabetes in subjects with 1hPG ≥8.85 mmol/L was higher than those <8.85 mmol/L (46.2% vs 3.3%, P = 0.000; relative risk 13.846, 95% confidence interval 4.223–45.400). On follow up, the prevalence of metabolic syndrome and abnormal carotid intima-media thickness in the subjects with 1hPG ≥8.85 mmol/L tended to be higher compared with those <8.85 mmol/L. Conclusions 1hPG is a good predictor of type 2 diabetes in NGR subjects, and the best cut-off point is 8.85 mmol/L. Some tendency indicates that NGR subjects with 1hPG ≥8.85 mmol/L are more prone to metabolic syndrome and carotid atherosclerosis. PMID:26543538

  2. Depressive symptoms linked to 1-h plasma glucose concentrations during the oral glucose tolerance test in men and women with the metabolic syndrome

    PubMed Central

    Birnbaum-Weitzman, O.; Goldberg, R.; Hurwitz, B. E.; Llabre, M. M.; Gellman, M. D.; Gutt, M.; McCalla, J. R.; Mendez, A. J.; Schneiderman, N.

    2014-01-01

    Aims The addition of the 1-h plasma glucose concentration measure from an oral glucose tolerance test to prediction models of future Type 2 diabetes has shown to significantly strengthen their predictive power. The present study examined the relationship between severity of depressive symptoms and hyperglycaemia, focusing on the 1-h glucose concentration vs. fasting and 2-h oral glucose tolerance test glucose measures. Methods Participants included 140 adults with the metabolic syndrome and without diabetes who completed a baseline psychobiological assessment and a 2-h oral glucose tolerance test, with measurements taken every 30 min. Depressive symptoms were assessed using the Beck Depression Inventory. Results Multivariate linear regression revealed that higher levels of depressive symptoms were associated with higher levels of 1-h plasma glucose concentrations after adjusting for age, gender, ethnicity, BMI, antidepressant use and high-sensitivity C-reactive protein. Results were maintained after controlling for fasting glucose as well as for indices of insulin resistance and secretion. Neither fasting nor 2-h plasma glucose concentrations were significantly associated with depressive symptoms. Conclusions Elevated depressive symptoms in persons with the metabolic syndrome were associated with greater glycaemic excursion 1-h following a glucose load that was not accounted for by differences in insulin secretory function or insulin sensitivity. Consistent with previous findings, this study highlights the value of the 1-h oral glucose tolerance test plasma glucose measurement in the relation between depressive symptoms and glucose metabolism as an indicator of metabolic abnormalities not visible when focusing on fasting and 2-h post-oral glucose tolerance test measurements alone. PMID:24344735

  3. Metabolomic analysis of the plasma of patients with high-altitude pulmonary edema (HAPE) using 1H NMR.

    PubMed

    Luo, Yongjun; Zhu, Junyu; Gao, Yuqi

    2012-06-01

    Upon rapid ascent to a high altitude, non-acclimatized individuals, although healthy, are highly prone to contracting high-altitude pulmonary edema (HAPE). Early diagnosis is difficult and there is no reliable biomarker available. We used proton ((1)H) NMR metabolomics to profile the altered metabolic patterns of blood plasma from HAPE patients. The plasmas of ten patients with HAPE and ten individuals without HAPE were collected and compared using (1)H NMR spectroscopy. Data were evaluated with several multivariate statistical analyses, including the principal components, the orthogonal partial least-squares discriminant, and the orthogonal signal correction partial least-squares discriminant. Multivariate statistical analyses revealed a significant disparity between subjects with HAPE and those in the control group. Compared to the plasma of the controls, the HAPE patients had significant increases in valine, lysine, leucine, isoleucine, glycerol phosphoryl choline, glycine, glutamine, glutamic acid, creatinine, citrate, and methyl histidine. These were accompanied by decreases in α- and β-glucose, trimethylamine, and the metabolic products of lipids. The data demonstrate that metabolomics may be effective for the diagnosis of HAPE in the future, and can be used for further understanding HAPE pathogenesis. PMID:22498880

  4. Diabetic neuropathy and plasma glucose control.

    PubMed

    Porte, D; Graf, R J; Halter, J B; Pfeifer, M A; Halar, E

    1981-01-01

    Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes. PMID:7457487

  5. 1H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver

    PubMed Central

    Xu, Chuang; Sun, Ling-wei; Xia, Cheng; Zhang, Hong-you; Zheng, Jia-san; Wang, Jun-song

    2016-01-01

    Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using 1H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows. PMID:26732447

  6. (1)H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver.

    PubMed

    Xu, Chuang; Sun, Ling-Wei; Xia, Cheng; Zhang, Hong-You; Zheng, Jia-San; Wang, Jun-Song

    2016-02-01

    Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using (1)H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows. PMID:26732447

  7. Identification of 2-Fluoro-2-deoxy- D-glucose Metabolites by 19F{ 1H} Hetero-RELAY

    NASA Astrophysics Data System (ADS)

    O'Connell, Thomas M.; London, Robert E.

    1995-12-01

    It has been proposed that in mammalian systems the glucose analog 2-fluoro-2-deoxy-D-glucose (FDG) is phosphoryated and subsequently converted to the corresponding mannose derivative via the action of phosphoglucose isomerase. As is generally true in metabolic studies of fluorinated molecules, the fluorine spectrum alone is suggestive, without providing definitive structural evidence, while the use of1H NMR techniques generally suffers from a lack of adequate selectivity. A1H-19F version of the hetero-RELAY experiment has been applied to this problem. Formation of the corresponding C-6 phosphorylated 2-FDG analog with hexokinase, followed by treatment of the resulting phosphorylated products with phosphoglucose isomerase, resulted in the observation of additional19F resonances consistent with the corresponding 2-fluoro-2-deoxy-D-mannose-6-phosphate metabolite. A more definitive product identification was obtained using the hetero-RELAY experiment, which provides a complete19F-decoupled proton spectrum for each of the fluorinated species.

  8. One-Hour Postload Plasma Glucose Levels Are Associated with Kidney Dysfunction

    PubMed Central

    Succurro, Elena; Arturi, Franco; Lugarà, Marina; Grembiale, Alessandro; Fiorentino, Teresa Vanessa; Caruso, Vittoria; Andreozzi, Francesco; Sciacqua, Angela; Hribal, Marta Letizia; Perticone, Francesco

    2010-01-01

    Background and objectives: A cutoff of 155 mg/dl for 1-hour postload plasma glucose (1hPG) during the oral glucose tolerance test (OGTT) is able to identify patients who are at high risk for type 2 diabetes and vascular atherosclerosis. We aimed to examine whether individuals with 1hPG ≥155 mg/dl are also at increased risk for chronic kidney disease (CKD). Design, setting, participants, & measurements: Atherosclerosis risk factors, OGTT, and estimated GFR by Chronic Kidney Disease Epidemiology Collaboration equation were analyzed in 1075 white individuals without diabetes. Results: The area under the receiver operating characteristic curve for 1hPG was the highest (0.700) compared with the areas under the receiver operating characteristic curve of 0, 30-minute, and 2-hour glucose concentrations. Individuals with 1hPG ≥155 mg/dl had a worse cardiometabolic risk profile, exhibiting significantly higher body mass index, BP, triglycerides, and fasting insulin levels and lower HDL, IGF-1 levels, and insulin sensitivity, than individuals with 1hPG <155 mg/dl. Estimated GFR was significantly lower in individuals with 1hPG ≥155 mg/dl. In a logistic regression model adjusted for age and gender, individuals with 1hPG ≥155 mg/dl showed an increased risk for CKD compared with individuals with 1hPG <155 mg/dl. When the logistic regression analysis was restricted to individuals who had normal glucose tolerance, those with 1hPG ≥155 mg/dl showed a higher risk for CKD compared with individuals with 1hPG <155 mg/dl. Conclusions: These data suggest that a cutoff point of 155 mg/dl for the 1hPG during OGTT may be helpful in the identification of individuals who are at increased risk for CKD. PMID:20595688

  9. Misled by the Morning "Fasting" Plasma Glucose.

    PubMed

    King, Allen B

    2015-11-01

    Because of its ease and simplicity of its measurement, the morning fasting plasma glucose (FPG), has been as used a surrogate marker for the entire basal day when titrating once-nightly basal insulin. Common in obese insulin-treated patients with type 2 diabetes, late and large evening meals elevate the FPG. This has led to dosing of basal insulin well beyond the basal requirements and contributes to hypoglycemia and weight gain seen with this therapy. It is recommended that during basal insulin titration, the evening meal be limited and hypoglycemia be monitored early in the morning, that bewitching time when the "peakless" basal insulin's action is peaking and the predawn phenomenon insulin sensitivity is higher. PMID:25972281

  10. Association between One-Hour Post-Load Plasma Glucose Levels and Vascular Stiffness in Essential Hypertension

    PubMed Central

    Sciacqua, Angela; Maio, Raffaele; Miceli, Sofia; Pascale, Alessandra; Carullo, Giuseppe; Grillo, Nadia; Arturi, Franco; Sesti, Giorgio; Perticone, Francesco

    2012-01-01

    Objectives Pulse wave velocity (PWV) is a surrogate end-point for cardiovascular morbidity and mortality. A plasma glucose value ≥155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes (T2D) and for subclinical organ damage. Thus, we addressed the question if 1-hour post-load plasma glucose levels, affects PWV and its central hemodynamic correlates, as augmentation pressure (AP) and augmentation index (AI). Methods We enrolled 584 newly diagnosed hypertensives. All patients underwent OGTT and measurements of PWV, AP and AI. Insulin sensitivity was assessed by Matsuda-index. Results Among participants, 424 were NGT and 160 had impaired glucose tolerance (IGT). Of 424 NGT, 278 had 1-h post-load plasma glucose <155 mg/dl (NGT<155) and 146 had 1-h post-load plasma glucose ≥155 mg/dl (NGT≥155). NGT≥155 had a worse insulin sensitivity and higher hs-CRP than NGT<155, similar to IGT subjects. In addition, NGT ≥155 in comparison with NGT<155 had higher central systolic blood pressure (134±12 vs 131±10 mmHg), as well as PWV (8.4±3.7 vs 6.7±1.7 m/s), AP (12.5±7.1 vs 9.8±5.7 mmHg) and AI (29.4±11.9 vs 25.1±12.4%), and similar to IGT. At multiple regression analysis, 1-h post-load plasma glucose resulted the major determinant of all indices of vascular stiffness. Conclusion Hypertensive NGT≥155 subjects, compared with NGT<155, have higher PWV and its hemodynamic correlates that increase their cardiovascular risk profile. PMID:23028545

  11. Design of a sup 13 C (1H) RF probe for monitoring the in vivo metabolism of (1- sup 13 C)glucose in primate brain

    SciTech Connect

    Hammer, B.E.; Sacks, W.; Bigler, R.E.; Hennessy, M.J.; Sacks, S.; Fleischer, A.; Zanzonico, P.B. )

    1990-01-01

    The design of an RF probe suitable for obtaining proton-decoupled {sup 13}C spectra from a subhuman primate brain is described. Two orthogonal saddle coils, one tuned to the resonant frequency of {sup 13}C and the other to the resonant frequency of 1H, were used to monitor the in vivo metabolism of (1-{sup 13}C)glucose in rhesus monkey brain at 2.1 T. Difference spectra showed the appearance of {sup 13}C-enriched glutamate and glutamine 30 to 40 min after a bolus injection of (1-{sup 13}C)glucose.

  12. Effects of fasting on plasma glucose and prolonged tracer measurement of hepatic glucose output in NIDDM

    SciTech Connect

    Glauber, H.; Wallace, P.; Brechtel, G.

    1987-10-01

    We studied the measurement of hepatic glucose output (HGO) with prolonged (3-/sup 3/H)glucose infusion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM). Over the course of 10.5 h, plasma glucose concentration fell with fasting by one-third, from 234 +/- 21 to 152 +/- 12 mg/dl, and HGO fell from 2.35 +/- 0.18 to 1.36 +/- 0.07 mg . kg-1 . min-1 (P less than .001). In the basal state, HGO and glucose were significantly correlated (r = 0.68, P = .03), and in individual patients, HGO and glucose were closely correlated as both fell with fasting (mean r = 0.79, P less than .01). Plasma (3-/sup 3/H)glucose radioactivity approached a steady state only 5-6 h after initiation of the primed continuous infusion, and a 20% overestimate of HGO was demonstrated by not allowing sufficient time for tracer labeling of the glucose pool. Assumption of steady-state instead of non-steady-state kinetics in using Steele's equations to calculate glucose turnover resulted in a 9-24% overestimate of HGO. Stimulation of glycogenolysis by glucagon injection demonstrated no incorporation of (3-/sup 3/H)glucose in hepatic glycogen during the prolonged tracer infusion. In a separate study, plasma glucose was maintained at fasting levels (207 +/- 17 mg/dl) for 8 h with the glucose-clamp technique. Total glucose turnover rates remained constant during this prolonged tracer infusion. However, HGO fell to 30% of the basal value simply by maintaining fasting hyperglycemia in the presence of basal insulin levels.

  13. Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen–glucose deprivation in a neonatal brain slice model of asphyxia

    PubMed Central

    Liu, Jia; Litt, Lawrence; Segal, Mark R; Kelly, Mark J S; Yoshihara, Hikari A I; James, Thomas L

    2011-01-01

    Human clinical trials using 72 hours of mild hypothermia (32°C–34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that 1H/31P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen–glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the 1H spectra included PCr-1H (phosphocreatine in the 1H spectrum), ATP-1H (adenosine triphosphate in the 1H spectrum), and ADP-1H (adenosine diphosphate in the 1H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia. PMID:20717124

  14. Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen-glucose deprivation in a neonatal brain slice model of asphyxia.

    PubMed

    Liu, Jia; Litt, Lawrence; Segal, Mark R; Kelly, Mark J S; Yoshihara, Hikari A I; James, Thomas L

    2011-02-01

    Human clinical trials using 72 hours of mild hypothermia (32°C-34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that (1)H/(31)P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen-glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the (1)H spectra included PCr-(1)H (phosphocreatine in the (1)H spectrum), ATP-(1)H (adenosine triphosphate in the (1)H spectrum), and ADP-(1)H (adenosine diphosphate in the (1)H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia. PMID:20717124

  15. Normal fasting plasma glucose levels in some birds of prey.

    PubMed

    O'Donnell, J A; Garbett, R; Morzenti, A

    1978-10-01

    Blood samples taken from five great horned owls (Bubo virginianus), eight red-tailed hawks (Buteo jamaicensis), four marsh hawks (Circus cyaneus), two prairie falcons (Falco mexicanus), five golden eagles (Aquila chrysaetos), and five white leghorn chickens (Gallus domesticus) that had been fasted for 24 h were used to determine plasma levels of glucose by the glucose oxidase method. The mean plasma glucose levels were: great horned owls 374.6 mg/100 ml, red-tailed hawks 346.5 mg/00 ml, marsh hawks 369.3 mg/100 ml, prairie falcons 414.5 mg/100 ml, golden eagles 368.4 mg/100 ml, and white Leghorn chickens 218.2 mg/100 ml. The plasma glucose levels obtained for the raptorial birds in this study were considerably higher than those found for the chickens. These values are discussed in relation to the carnivorous food habits of raptors. PMID:739587

  16. Gestational diabetes mellitus: Screening with fasting plasma glucose.

    PubMed

    Agarwal, Mukesh M

    2016-07-25

    Fasting plasma glucose (FPG) as a screening test for gestational diabetes mellitus (GDM) has had a checkered history. During the last three decades, a few initial anecdotal reports have given way to the recent well-conducted studies. This review: (1) traces the history; (2) weighs the advantages and disadvantages; (3) addresses the significance in early pregnancy; (4) underscores the benefits after delivery; and (5) emphasizes the cost savings of using the FPG in the screening of GDM. It also highlights the utility of fasting capillary glucose and stresses the value of the FPG in circumventing the cumbersome oral glucose tolerance test. An understanding of all the caveats is crucial to be able to use the FPG for investigating glucose intolerance in pregnancy. Thus, all health professionals can use the patient-friendly FPG to simplify the onerous algorithms available for the screening and diagnosis of GDM - thereby helping each and every pregnant woman. PMID:27525055

  17. Gestational diabetes mellitus: Screening with fasting plasma glucose

    PubMed Central

    Agarwal, Mukesh M

    2016-01-01

    Fasting plasma glucose (FPG) as a screening test for gestational diabetes mellitus (GDM) has had a checkered history. During the last three decades, a few initial anecdotal reports have given way to the recent well-conducted studies. This review: (1) traces the history; (2) weighs the advantages and disadvantages; (3) addresses the significance in early pregnancy; (4) underscores the benefits after delivery; and (5) emphasizes the cost savings of using the FPG in the screening of GDM. It also highlights the utility of fasting capillary glucose and stresses the value of the FPG in circumventing the cumbersome oral glucose tolerance test. An understanding of all the caveats is crucial to be able to use the FPG for investigating glucose intolerance in pregnancy. Thus, all health professionals can use the patient-friendly FPG to simplify the onerous algorithms available for the screening and diagnosis of GDM - thereby helping each and every pregnant woman. PMID:27525055

  18. D-Glucose-recognition and phlorizin-binding sites in human sodium/D-glucose cotransporter 1 (hSGLT1): a tryptophan scanning study.

    PubMed

    Tyagi, Navneet K; Kumar, Azad; Goyal, Pankaj; Pandey, Dharmendra; Siess, Wolfgang; Kinne, Rolf K H

    2007-11-27

    In order to gain a better understanding of the structure-function relation in hSGLT1, single Trp residues were introduced into a functional hSGLT1 mutant devoid of Trps at positions that previously had been postulated to be involved in sugar recognition/translocation and/or phlorizin binding. The mutant proteins were expressed in Pichia pastoris, purified, and reconstituted into liposomes. In transport experiments the putative sugar binding site mutants W457hSGLT1 and W460hSGLT1 showed a drastic decrease in affinity toward alpha-methyl-d-glucopyranoside with Km values of 13.3 and 5.26 mM compared to 0.4 mM of the Trp-less hSGLT1. In addition, a strong decrease in the inhibitory effect of phlorizin was observed. In Trp fluorescence studies the position of the emission maxima of the mutants, their sensitivity to N-bromosuccinimide oxidation, and their interaction with water soluble quenchers demonstrate that Trp457 and Trp460 are in contact with the hydrophilic extravesicular environment. In both mutants Trp fluorescence was quenched significantly, but differently, by various glucose analogues. They also show significant protection by d-glucose and phlorizin against acrylamide, KI, or TCE quenching. W602hSGLT1 and W609hSGLT1, the putative aglucone binding site mutants, exhibit normal sugar and phlorizin affinity, and show fluorescence properties which indicate that these residues are located in a very hydrophilic environment. Phlorizin and phloretin, but not d-glucose, protect both mutants against collisional quenchers. Depth-calculations using the parallax method suggest a location of Trp457 and Trp460 at an average distance of 10.8 A and 7.4 A from the center of the bilayer, while Trp602 and Trp609 are located outside the membrane. These results suggest that in the native carrier residues Gln at position 457 and Thr at position 460 reside in a hydrophilic access pathway extending 5-7 A into the membrane to which sugars as well as the sugar moiety of inhibitory

  19. Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations

    PubMed Central

    Sinxadi, Phumla Zuleika; McIlleron, Helen Margaret; Dave, Joel Alex; Smith, Peter John; Levitt, Naomi Sharlene; Haas, David William; Maartens, Gary

    2016-01-01

    Abstract Efavirenz-based antiretroviral therapy (ART) has been associated with dyslipidemia and dysglycemia, risk factors for cardiovascular disease. However, the pathogenesis is not well understood. We characterized relationships between plasma efavirenz concentrations and lipid and glucose concentrations in HIV-infected South Africans. Participants on efavirenz-based ART were enrolled into a cross-sectional study. The oral glucose tolerance test was performed after an overnight fast, and plasma drawn for mid-dosing interval efavirenz, fasting total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides concentrations. Among 106 participants (77 women), median age was 38 years, median CD4 + T-cell count was 322 cells/μL, median duration on ART was 18 months, and median (interquartile range) efavirenz concentration was 2.23 (1.66 to 4.10) μg/mL. On multivariable analyses (adjusting for age, sex, body mass index, and ART duration) doubling of efavirenz concentrations resulted in mean changes in mmol/L (95%CI) of: total cholesterol (0.40 [0.22 to 0.59]), LDL cholesterol (0.19 [0.04 to 0.30]), HDL cholesterol (0.14 [0.07 to 0.20]), triglycerides (0.17 [0.03 to 0.33]), fasting glucose (0.18 [0.03 to 0.33]), and 2-h glucose concentrations (0.33 [0.08 to 0.60]). Among 57 participants with CYP2B6 genotype data, associations between slow metabolizer genotypes and metabolic profiles were generally consistent with those for measured efavirenz concentrations. Higher plasma efavirenz concentrations are associated with higher plasma lipid and glucose concentrations. This may have implications for long-term cardiovascular complications of efavirenz-based ART, particularly among populations with high prevalence of CYP2B6 slow metabolizer genotypes. PMID:26765416

  20. Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations.

    PubMed

    Sinxadi, Phumla Zuleika; McIlleron, Helen Margaret; Dave, Joel Alex; Smith, Peter John; Levitt, Naomi Sharlene; Haas, David William; Maartens, Gary

    2016-01-01

    Efavirenz-based antiretroviral therapy (ART) has been associated with dyslipidemia and dysglycemia, risk factors for cardiovascular disease. However, the pathogenesis is not well understood. We characterized relationships between plasma efavirenz concentrations and lipid and glucose concentrations in HIV-infected South Africans.Participants on efavirenz-based ART were enrolled into a cross-sectional study. The oral glucose tolerance test was performed after an overnight fast, and plasma drawn for mid-dosing interval efavirenz, fasting total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides concentrations.Among 106 participants (77 women), median age was 38 years, median CD4 + T-cell count was 322 cells/μL, median duration on ART was 18 months, and median (interquartile range) efavirenz concentration was 2.23 (1.66 to 4.10) μg/mL. On multivariable analyses (adjusting for age, sex, body mass index, and ART duration) doubling of efavirenz concentrations resulted in mean changes in mmol/L (95%CI) of: total cholesterol (0.40 [0.22 to 0.59]), LDL cholesterol (0.19 [0.04 to 0.30]), HDL cholesterol (0.14 [0.07 to 0.20]), triglycerides (0.17 [0.03 to 0.33]), fasting glucose (0.18 [0.03 to 0.33]), and 2-h glucose concentrations (0.33 [0.08 to 0.60]). Among 57 participants with CYP2B6 genotype data, associations between slow metabolizer genotypes and metabolic profiles were generally consistent with those for measured efavirenz concentrations.Higher plasma efavirenz concentrations are associated with higher plasma lipid and glucose concentrations. This may have implications for long-term cardiovascular complications of efavirenz-based ART, particularly among populations with high prevalence of CYP2B6 slow metabolizer genotypes. PMID:26765416

  1. 1H NMR-Based Metabolite Profiling of Plasma in a Rat Model of Chronic Kidney Disease

    PubMed Central

    Kim, Ju-Ae; Choi, Hyo-Jung; Kwon, Yong-Kook; Ryu, Do Hyun; Kwon, Tae-Hwan; Hwang, Geum-Sook

    2014-01-01

    Chronic kidney disease (CKD) is characterized by the gradual loss of the kidney function to excrete wastes and fluids from the blood. 1H NMR-based metabolomics was exploited to investigate the altered metabolic pattern in rats with CKD induced by surgical reduction of the renal mass (i.e., 5/6 nephrectomy (5/6 Nx)), particularly for identifying specific metabolic biomarkers associated with early of CKD. Plasma metabolite profiling was performed in CKD rats (at 4- or 8-weeks after 5/6 Nx) compared to sham-operated rats. Principle components analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots showed a significant separation between the groups. The resulting metabolic profiles demonstrated significantly increased plasma levels of organic anions, including citrate, β-hydroxybutyrate, lactate, acetate, acetoacetate, and formate in CKD. Moreover, levels of alanine, glutamine, and glutamate were significantly higher. These changes were likely to be associated with complicated metabolic acidosis in CKD for counteracting systemic metabolic acidosis or increased protein catabolism from muscle. In contrast, levels of VLDL/LDL (CH2)n and N-acetylglycoproteins were decreased. Taken together, the observed changes of plasma metabolite profiles in CKD rats provide insights into the disturbed metabolism in early phase of CKD, in particular for the altered metabolism of acid-base and/or amino acids. PMID:24465563

  2. The relationship of plasma glucose and electrocardiographic parameters in elderly women with different degrees of glucose tolerance.

    PubMed

    Solini, A; Passaro, A; D'Elia, K; Calzoni, F; Alberti, L; Fellin, R

    2000-08-01

    Plasma glucose has been regarded as a risk factor for macrovascular complications in diabetes, but less is known about its role in the development of cardiac impairment other than coronary heart disease (CHD). The aim of our study was to determine the relationship between basal and post-OGTT (Oral Glucose Tolerance Test) plasma glucose levels and some ECG parameters in a group of elderly women with normal or impaired glucose tolerance (IGT). One-hundred and one women with normal fasting glucose (<6.0 mmol/L) and no familial history or clinical signs of CHD and diabetes underwent an OGTT and a resting ECG. Based on the degree of glucose tolerance, we identified 24 women with a diagnostic OGTT for either IGT or diabetes; the 77 women (age range 52-88 years) with normal glucose tolerance were further divided into two groups according to their post-OGTT area under the curve (AUCG): below and above the median value (32 and 45 women, respectively). Basal plasma glucose and insulin levels, as well as lipid profile and percent of hypertensive patients were similar in the three groups. Mean corrected QT (QTc) was prolonged as a function of progressive worsening of glucose tolerance even after adjustment for possible confounding factors (p=0.03). A similar relationship was apparent when post-OGTT plasma glucose peak (GP) was considered. In a multiple regression analysis, AUCG and GP were the only factors independently related to both QTc and Sokolow index. Our observations suggest that, even in the presence of a normal glucose tolerance, plasma glucose concentrations during an OGTT are associated with peculiar ECG signs potentially combined with an increased risk of sudden death, arrhythmias, or cardiovascular mortality. PMID:11073343

  3. Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

    PubMed Central

    Fan, Fan; Ji, Chen; Wu, Yumei; Ferguson, Shawn M.; Tamarina, Natalia; Philipson, Louis H.; Lou, Xuelin

    2015-01-01

    Alterations in insulin granule exocytosis and endocytosis are paramount to pancreatic β cell dysfunction in diabetes mellitus. Here, using temporally controlled gene ablation specifically in β cells in mice, we identified an essential role of dynamin 2 GTPase in preserving normal biphasic insulin secretion and blood glucose homeostasis. Dynamin 2 deletion in β cells caused glucose intolerance and substantial reduction of the second phase of glucose-stimulated insulin secretion (GSIS); however, mutant β cells still maintained abundant insulin granules, with no signs of cell surface expansion. Compared with control β cells, real-time capacitance measurements demonstrated that exocytosis-endocytosis coupling was less efficient but not abolished; clathrin-mediated endocytosis (CME) was severely impaired at the step of membrane fission, which resulted in accumulation of clathrin-coated endocytic intermediates on the plasma membrane. Moreover, dynamin 2 ablation in β cells led to striking reorganization and enhancement of actin filaments, and insulin granule recruitment and mobilization were impaired at the later stage of GSIS. Together, our results demonstrate that dynamin 2 regulates insulin secretory capacity and dynamics in vivo through a mechanism depending on CME and F-actin remodeling. Moreover, this study indicates a potential pathophysiological link between endocytosis and diabetes mellitus. PMID:26413867

  4. Gluconeogenesis is not acutely regulated by either plasma glucose or plasma insulin concentration in parenterally fed ELBW infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parenterally fed ELBW infants often exhibit erratic regulation of plasma glucose levels in response to changes in glucose infusion rate. This apparent dysregulation could be the result of an inappropriate insulin secretory response, incomplete suppression of glucose production, or an inadequate chan...

  5. Alcohol, postprandial plasma glucose, and prognosis of hepatocellular carcinoma

    PubMed Central

    Abe, Hiroshi; Aida, Yuta; Ishiguro, Haruya; Yoshizawa, Kai; Miyazaki, Tamihiro; Itagaki, Munenori; Sutoh, Satoshi; Aizawa, Yoshio

    2013-01-01

    AIM: To identify factors associated with prognosis of hepatocellular carcinoma (HCC) after initial therapy. METHODS: A total of 377 HCC patients who were newly treated at Katsushika Medical Center, Japan from January 2000 to December 2009 and followed up for > 2 years, or died during follow-up, were enrolled. The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis. A similar analysis was performed in 282 patients with tumor stage T1-T3. Additionally, factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence. Finally, 214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels, and differences in their causes of death were examined. RESULTS: On multivariate Cox proportional hazards regression analysis, the following were significantly associated with survival: underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C, hazard ratio (HR): 0.603, 95% CI: 0.417-0.874, P = 0.0079], HCC stage (T1/T2 vs T3/T4, HR: 0.447, 95% CI: 0.347-0.576, P < 0.0001), and mean postprandial plasma glucose after initial therapy (< 200 vs ≥ 200 mg/dL, HR: 0.181, 95% CI: 0.067-0.488, P = 0.0008). In T1-T3 patients, uninterrupted alcohol consumption after initial therapy (no vs yes, HR: 0.641, 95% CI: 0.469-0.877, P = 0.0055) was significant in addition to underlying liver disease stage (non-cirrhosis/Child-Pugh A vs B/C, HR: 0649, 95% CI: 0.476-0.885, P = 0.0068), HCC stage (T1 vs T2/T3, HR: 0.788, 95% CI: 0.653-0.945, P = 0.0108), and mean postprandial plasma glucose after initial therapy (< 200 mg/dL vs ≥ 200 mg/dL, HR: 0.502, 95% CI: 0.337-0.747, P = 0.0005). In patients without local recurrence, time from initial to subsequent therapy for newly emerging HCC was significantly longer in

  6. Response to fifty grams oral glucose challenge test and pattern of preceding fasting plasma glucose in normal pregnant Nigerians

    PubMed Central

    Ajayi, Godwin Olufemi

    2014-01-01

    Background: Diabetes mellitus in pregnancy has profound implications for the baby and mother and thus active screening for this is desirable. Method: Fifty grams oral glucose challenge test was administered after obtaining consent to 222 women in good health with singleton pregnancies without diabetes mellitus at 24 to 28 weeks gestation after an overnight fast. Venous blood sample was obtained before and 1 hour after the glucose load. A diagnostic 3-hour 100 g oral glucose tolerance test was subsequently performed in all. Results: Two hundred and ten women had a normal response to oral glucose tolerance test i.e. venous plasma glucose below these cut-off levels: fasting 95 mg/dl (5.3 mmol/l), 1 hour 180 mg/dl (10.0 mmol/l), 2 hours 155 mg/dl (8.6 mmol/l) and 3 hours 140 mg/dl (7.8 mmol/l), while 12 were found to have gestational diabetes mellitus and were subsequently excluded from the study. They were appropriately managed. The mean maternal age was 30.9 ± 4.1 years (range 19 to 45 years) and the mean parity was 1.2 ± 1.1 (range 0 to 5). The mean fasting plasma glucose was 74.5 ± 11.5 mg/dl (range 42 to 117 mg/dl), while the mean plasma glucose 1 hour after 50 g glucose challenge test was 115.3 ± 19.1 mg/dl (range 56 to 180 mg/dl). Conclusions: The mean fasting plasma glucose in normal pregnant Nigerians was 74.5 ± 11.5 mg/dl (range 42 to 117 mg/dl). There is a need to re-appraise and possibly review downwards the World Health Organization fasting plasma glucose diagnostic criteria in pregnant Nigerians for better detection of gestational diabetes mellitus. Pregnant women with venous plasma glucose greater than 153.5 mg/dl (8.5 mmol/l) 1 hour after 50 g glucose challenge test are strongly recommended for diagnostic test of gestational diabetes mellitus.

  7. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

    PubMed

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2016-09-01

    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice. PMID:27430421

  8. Plasma cortisol and glucose concentrations in the striped mullet ( Mugil cephalus L.) subjected to intense handling stress

    NASA Astrophysics Data System (ADS)

    Hong, Wanshu

    1992-03-01

    The plasma cortisol and glucose concentrations were determined in mature female striped mullet ( Mugil cephalus L.) subjected to short term intense handling stress. The results indicated that plasma cortisol levels reached a peak 20 min after stress and declined gradually afterwards. The highest concentration of plasma glucose was observed 30 min after stress. The present study showed that the rise of plasma glucose was associated with the plasma cortisol levels.

  9. Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.

    PubMed

    Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J

    2015-01-01

    Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations. PMID:26435060

  10. Glycaemia regulates the glucose transporter number in the plasma membrane of rat skeletal muscle.

    PubMed Central

    Dimitrakoudis, D; Ramlal, T; Rastogi, S; Vranic, M; Klip, A

    1992-01-01

    The number of glucose transporters was measured in isolated membranes from diabetic-rat skeletal muscle to determine the role of circulating blood glucose levels in the control of glucose uptake into skeletal muscle. Three experimental groups of animals were investigated in the post-absorptive state: normoglycaemic/normoinsulinaemic, hyperglycaemic/normoinsulinaemic and hyperglycaemic/normoinsulinaemic made normoglycaemic/normoinsulinaemic by phlorizin treatment. Hyperglycaemia caused a reversible decrease in total transporter number, as measured by cytochalasin B binding, in both plasma membranes and internal membranes of skeletal muscle. Changes in GLUT4 glucose transporter protein mirrored changes in cytochalasin B binding in plasma membranes. However, there was no recovery of GLUT4 levels in intracellular membranes with correction of glycaemia. GLUT4 mRNA levels decreased with hyperglycaemia and recovered only partially with correction of glycaemia. Conversely, GLUT1 glucose transporters were only detectable in the plasma membranes; the levels of this protein varied directly with glycaemia, i.e. in the opposite direction to GLUT4 glucose transporters. This study demonstrates that hyperglycaemia, in the absence of hypoinsulinaemia, is capable of down-regulating the glucose transport system in skeletal muscle, the major site of peripheral resistance to insulin-stimulated glucose transport in diabetes. Furthermore, correction of hyperglycaemia causes a complete restoration of the transport system in the basal state (determined by the transporter number in the plasma membrane), but possibly only an incomplete recovery of the transport system's ability to respond to insulin (since there is no recovery of GLUT4 levels in the intracellular membrane insulin-responsive transporter pool). Finally, the effect of hyperglycaemia is specific for glucose transporter isoforms, with GLUT1 and GLUT4 proteins varying respectively in parallel and opposite directions to levels of

  11. An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults.

    PubMed

    Rivas, Eric; Newmire, Dan E; Crandall, Craig G; Hooper, Philip L; Ben-Ezra, Vic

    2016-07-01

    Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45±7.1% fat mass) type 2 diabetics (T2DM: 50.1±12y, 7.5±1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1±13.7y) healthy non-obese controls (HC: 33.4±7.8% fat mass, P<0.01; 5.3±0.4% HbA1c, P<0.01) participated. Using a randomized design, subjects underwent either a whole body passive hyperthermia treatment via head-out hot water immersion (1h resting in 39.4±0.4°C water) that increased internal temperature above baseline by ∆1.6±0.4°C or a control resting condition. Twenty-four hours post treatments, a 75g OGTT was administered to evaluate changes in plasma glucose, insulin, C-peptide, and leptin concentrations. Hyperthermia itself did not alter area under the curve for plasma glucose, insulin, or C-peptide during the OGTT in either group. Fasting absolute and normalized (kg·fat mass) plasma leptin was significantly increased (P<0.01) only after the hyperthermic exposure by 17% in T2DM and 24% in HC groups (P<0.001) when compared to the control condition. These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals. PMID:27264884

  12. Higher fasting plasma glucose is associated with striatal and hippocampal shape differences: the 2sweet project

    PubMed Central

    Zhang, Tianqi; Shaw, Marnie; Humphries, Jacob; Sachdev, Perminder; Anstey, Kaarin J; Cherbuin, Nicolas

    2016-01-01

    Objective Previous studies have demonstrated associations between higher normal fasting plasma glucose levels (NFG) (<6.1 mmol/L), type 2 diabetes (T2D) and hippocampal atrophy and other cerebral abnormalities. Little is known about the association between plasma glucose and the striatum despite sensorimotor deficits being implicated in T2D. This study aimed to investigate the relationship between plasma glucose levels and striatal and hippocampal morphology using vertex-based shape analysis. Design A population-based, cross-sectional study. Setting Canberra and Queanbeyan, Australia. Participants 287 cognitively healthy individuals (mean age 63 years, 132 female, 273 Caucasian) with (n=261) or without T2D (n=26), selected from 2551 participants taking part in the Personality & Total Health (PATH) Through Life study by availability of glucose data, MRI scan, and absence of gross brain abnormalities and cognitive impairment. Outcome measures Fasting plasma glucose was measured at first assessment, and MRI images were collected 8 years later. Shape differences indicating outward and inward deformation at the hippocampus and the striatum were examined with FMRIB Software Library-Integrated Registration and Segmentation Toolbox (FSL-FIRST) after controlling for sociodemographic and health variables. Results Higher plasma glucose was associated with shape differences indicating inward deformation, particularly at the caudate and putamen, among participants with NFG after controlling for age, sex, body mass index (BMI), hypertension, smoking and depressive symptoms. Those with T2D showed shape differences indicating inward deformation at the right hippocampus and bilateral striatum, but outward deformation at the left hippocampus, compared with participants with NFG. Conclusions These findings further emphasize the importance of early monitoring and management of plasma glucose levels, even within the normal range, as a risk factor for cerebral atrophy. PMID

  13. Decrease in the plasma von Willebrand factor concentration following glucose ingestion: the role of insulin sensitivity.

    PubMed

    von Känel, R; Nelesen, R A; Le, D T; Ziegler, M G; Dimsdale, J E

    2001-12-01

    Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age +/- SD, 40 +/- 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI(0,120)). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r =.43, P =.005). There were time effects for all variables of interest. While vWF antigen (P =.044), epinephrine (P =.003), and diastolic BP (P =.001) decreased after glucose challenge, norepinephrine (P =.009), systolic BP (P =.022), and heart rate (P <.001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r =.46, P =.004) and with screening systolic BP (r =.45, P =.004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI(0,120.) The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance. PMID:11735092

  14. Plasma Glucose Levels for Red Drum Sciaenops Ocellatus in a Florida Estuarine Fisheries Reserve

    NASA Technical Reports Server (NTRS)

    Bourtis, Carla M.; Francis-Floyd, Ruth; Boggs, Ashley S P.; Reyier, Eric A.; Stolen, Eric D.; Yanong, Roy P.; Guillette, Louis J., Jr.

    2015-01-01

    Despite the significant value of the southeastern United States' red drum (Sciaenops ocellatus) fishery, there is a lack of clinical blood chemistry data. This was the first study to assess plasma glucose values as an indicator of stress response to evaluate variation and the effect of reproductive activity for wild adult red drum in Florida. Red drum (n=126) were collected from NASA's Kennedy Space Center waters during three reproductive periods in 2011. Samples were obtained from the branchial vessels of the gill arch. Plasma glucose levels were significantly different among reproductive periods, with the highest mean values recorded during the spawning period, September- October (38.23 mg / dL +/- 10.0). The glucose range was 17 - 69 mg / dL. Glucose values were lower during all three periods than previous values recorded for cultured or captive red drum studies. This may indicate that fish from this population were under less stress than other populations previously sampled.

  15. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults

    PubMed Central

    Aekplakorn, Wichai; Tantayotai, Valla; Numsangkul, Sakawduan; Sripho, Wilarwan; Tatsato, Nutchanat; Burapasiriwat, Tuanjai; Pipatsart, Rachada; Sansom, Premsuree; Luckanajantachote, Pranee; Chawarokorn, Pongpat; Thanonghan, Anek; Lakhamkaew, Watchira; Mungkung, Aungsumalin; Boonkean, Rungnapa; Chantapoon, Chanidsa; Kungsri, Mayuree; Luanseng, Kasetsak; Chaiyajit, Kornsinun

    2015-01-01

    Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG) and the 2 hr postprandial glucose tolerance test (OGTT) in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8%) individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.). The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed. PMID:26347060

  16. Real-time estimation of plasma insulin concentration from continuous glucose monitor measurements.

    PubMed

    de Pereda, Diego; Romero-Vivo, Sergio; Ricarte, Beatriz; Rossetti, Paolo; Ampudia-Blasco, Francisco Javier; Bondia, Jorge

    2016-01-01

    Continuous glucose monitors can measure interstitial glucose concentration in real time for closed-loop glucose control systems, known as artificial pancreas. These control systems use an insulin feedback to maintain plasma glucose concentration within a narrow and safe range, and thus to avoid health complications. As it is not possible to measure plasma insulin concentration in real time, insulin models have been used in literature to estimate them. Nevertheless, the significant inter- and intra-patient variability of insulin absorption jeopardizes the accuracy of these estimations. In order to reduce these limitations, our objective is to perform a real-time estimation of plasma insulin concentration from continuous glucose monitoring (CGM). Hovorka's glucose-insulin model has been incorporated in an extended Kalman filter in which different selected time-variant model parameters have been considered as extended states. The observability of the original Hovorka's model and of several extended models has been evaluated by their Lie derivatives. We have evaluated this methodology with an in-silico study with 100 patients with Type 1 diabetes during 25 h. Furthermore, it has been also validated using clinical data from 12 insulin pump patients with Type 1 diabetes who underwent four mixed meal studies. Real-time insulin estimations have been compared to plasma insulin measurements to assess performance showing the validity of the methodology here used in comparison with that formerly used for insulin models. Hence, real-time estimations for plasma insulin concentration based on subcutaneous glucose monitoring can be beneficial for increasing the efficiency of control algorithms for the artificial pancreas. PMID:26343364

  17. Glucose-Insulin Therapy, Plasma Substrate Levels and Cardiac Recovery After Cardiac Ischemic Events

    PubMed Central

    Van Wezel, H. B.

    2008-01-01

    Introduction The potential usefulness of glucose-insulin therapy relies to a large extent on the premise that it prevents hyperglycemia and hyperlipidemia following cardiac ischemic events. Methods In this review we evaluate the literature concerning plasma glucose and free fatty acids levels during and following cardiac ischemic events. Results The data indicate that hyperlipidemia and hyperglycemia most likely occur during acute coronary ischemic syndromes in the conscious state (e.g. acute myocardial infarction) and less so during reperfusion following CABG reperfusion. This is in accordance with observations that glucose-insulin therapy during early reperfusion post CABG may actually cause hypolipidemia, because substantial hyperlipidemia does not appear to occur during that stage of cardiac surgery. Discussion Considering recent data indicating that hypolipidemia may be detrimental for cardiac function, we propose that free fatty acid levels during reperfusion post CABG with the adjunct glucose-insulin therapy need to be closely monitored. Conclusion From a clinical point of view, a strategy directed at monitoring and thereafter maintaining plasma substrate levels in the normal range for both glucose (4–6 mM) and FFA (0.2–0.6 mM) as well as stimulation of glucose oxidation, promises to be the most optimal metabolic reperfusion treatment following cardiac ischemic episodes. Future (preclinical and subsequently clinical) investigations are required to investigate whether the combination of glucose-insulin therapy with concomitant lipid administration may be beneficial in the setting of reperfusion post CABG. PMID:18266096

  18. Plasma glucose kinetics and response of insulin and GIP following a cereal breakfast in female subjects: effect of starch digestibility

    PubMed Central

    Péronnet, F; Meynier, A; Sauvinet, V; Normand, S; Bourdon, E; Mignault, D; St-Pierre, D H; Laville, M; Rabasa-Lhoret, R; Vinoy, S

    2015-01-01

    Background/Objectives: Foods with high contents of slowly digestible starch (SDS) elicit lower glycemic responses than foods with low contents of SDS but there has been debate on the underlying changes in plasma glucose kinetics, that is, respective contributions of the increase in the rates of appearance and disappearance of plasma glucose (RaT and RdT), and of the increase in the rate of appearance of exogenous glucose (RaE) and decrease in endogenous glucose production (EGP). Subjects/Methods: Sixteen young healthy females ingested in random order four types of breakfasts: an extruded cereal (0.3% SDS: Lo-SDS breakfast) or one of three biscuits (39–45% SDS: Hi-SDS breakfasts). The flour in the cereal products was labeled with 13C, and plasma glucose kinetics were measured using [6,6-2H2]glucose infusion, along with the response of plasma glucose, insulin and glucose-dependent insulinotropic peptide (GIP) concentrations. Results: When compared with the Lo-SDS breakfast, after the three Hi-SDS breakfasts, excursions in plasma glucose, the response of RaE, RaT and RdT, and the reduction in EGP were significantly lower (P<0.05). The amount of exogenous glucose absorbed over the 4.5-h postprandial period was also significantly lower by ~31% (P<0.001). These differences were associated with lower responses of GIP and insulin concentrations. Conclusions: Substituting extruded cereals with biscuits slows down the availability of glucose from the breakfast and its appearance in peripheral circulation, blunts the changes in plasma glucose kinetics and homeostasis, reduces excursions in plasma glucose, and possibly distributes the glucose ingested over a longer period following the meal. PMID:25852025

  19. Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans

    PubMed Central

    Butler, Andrew A.; St-Onge, Marie-Pierre; Siebert, Emily A.; Medici, Valentina; Stanhope, Kimber L.; Havel, Peter J.

    2015-01-01

    Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations. PMID:26435060

  20. 13C and 31P chemical shielding tensors of a single crystal of dipotassium α- D-glucose-1-phosphate dihydrate. An application of a 13C-{ 1H, 31P} triple-resonance technique

    NASA Astrophysics Data System (ADS)

    McDowell, C. A.; Naito, A.; Sastry, D. L.; Takegoshi, K.

    The 13C NMR spectra of a single crystal of dipotassium α- D-glucose-l-phosphate dehydrate for different orientations in the external magnetic field, were recorded by using 1H and 31P double nuclear decoupling. To overcome difficulties encountered because of the high 13C RF power required to achieve the Hartmann-Hahn condition, a new cross-polarization method (K. Takegoshi and C. A. McDowell, J. Magn. Reson.67, 356 (1986)) was used. The directions of the most shielded principal value of the 13C chemical shielding tensors for the C2-C6 carbon nuclei in the glucose group were along the CO bond, and that for the CI carbon nucleus made an angle of 42† with the C1-O5 bond direction in the O1-C1-O5 plane. The 31P chemical shielding tensors are axially symmetric and the direction of the least shielded principal value is almost parallel to the P-O1(R) bond, which is the longest among the four PO bonds in the phosphate moiety.

  1. Performance of Fasting Plasma Glucose and Postprandial Urine Glucose in Screening for Diabetes in Chinese High-risk Population

    PubMed Central

    Yang, Bing-Quan; Lu, Yang; He, Jia-Jia; Wu, Tong-Zhi; Xie, Zuo-Ling; Lei, Cheng-Hao; Zhou, Yi; Han, Jing; Bian, Mei-Qi; You, Hong; Mei, De-Xian; Sun, Zi-Lin

    2015-01-01

    Background: The conventional approaches to diabetes screening are potentially limited by poor compliance and laboratory demand. This study aimed to evaluate the performance of fasting plasma glucose (FPG) and postprandial urine glucose (PUG) in screening for diabetes in Chinese high-risk population. Methods: Nine hundred and nine subjects with high-risk factors of diabetes underwent oral glucose tolerance test after an overnight fast. FPG, hemoglobin A1c, 2-h plasma glucose (2 h-PG), and 2 h-PUG were evaluated. Diabetes and prediabetes were defined by the American Diabetes Association criteria. The area under the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of 2 h-PUG, and the optimal cut-off determined to provide the largest Youden index. Spearman correlation was used for relationship analysis. Results: Among 909 subjects, 33.4% (304/909) of subjects had prediabetes, and 17.2% (156/909) had diabetes. The 2 h-PUG was positively related to FPG and 2 h-PG (r = 0.428 and 0.551, respectively, both P < 0.001). For estimation of 2 h-PG ≥ 7.8 mmol/L and 2 h-PG ≥ 11.1 mmol/L using 2 h-PUG, the area under the ROC curve were 0.772 (95% confidence interval [CI ]: 0.738–0.806) and 0.885 (95% CI: 0.850–0.921), respectively. The corresponding optimal cut-offs for 2 h-PUG were 5.6 mmol/L and 7.5 mmol/L, respectively. Compared with FPG alone, FPG combined with 2 h-PUG had a higher sensitivity for detecting glucose abnormalities (84.1% vs. 73.7%, P < 0.001) and diabetes (82.7% vs. 48.1%, P < 0.001). Conclusion: FPG combined with 2 h-PUG substantially improves the sensitivity in detecting prediabetes and diabetes relative to FPG alone, and may represent an efficient layperson-oriented diabetes screening method. PMID:26668139

  2. 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

  3. Urinary N-acetyl-β-d-Glucosaminidase Levels are Positively Correlated With 2-Hr Plasma Glucose Levels During Oral Glucose Tolerance Testing in Prediabetes

    PubMed Central

    Ouchi, Motoshi; Suzuki, Tatsuya; Hashimoto, Masao; Motoyama, Masayuki; Ohara, Makoto; Suzuki, Kazunari; Igari, Yoshimasa; Watanabe, Kentaro; Nakano, Hiroshi; Oba, Kenzo

    2012-01-01

    Background Urinary N-acetyl-β-D-glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT). This study investigated when during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose, and insulin levels correlate most strongly with urinary N-acetyl-β-d-glucosaminidase (NAG) levels in prediabetic subjects. Methods The OGTT was administered to 80 subjects who had not yet received a diagnosis of diabetes mellitus (DM) and in whom HbA1c levels were ≤6.8% and fasting plasma glucose levels were <7.0 mmol/l. Forty-two subjects had normal glucose tolerance (NGT), 31 had impaired glucose tolerance (IGT), and 7 had DM according to World Health Organization criteria. Serum levels of cystatin C, the estimated glomerular filtration rate, the urinary albumin-to-creatinine (Cr) ratio, urinary and serum β2-microglobulin, and urinary NAG were measured as markers of renal function. Results NAG levels were significantly higher in subjects with DM and in subjects with IGT than in subjects with NGT. No significant associations were observed between glycemic status and other markers of renal function. Multiple linear regression analysis showed that the NAG level was positively correlated with plasma glucose levels at 120 min of the OGTT and was associated with the glycemic status of prediabetic patients. Conclusion These results suggest that postprandial hyperglycemia is an independent factor that causes renal tubular damage in prediabetes patients. PMID:23143631

  4. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    PubMed

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), S I (Cau r = -0.51, P < 0.01; SA r = -0.41, P < 0.01), Φ dynamic (Cau r = -0.41, P < 0.01; SA r = -0.57, P < 0.01), and Φ oral (Cau r = -0.61, P < 0.01; SA r = -0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10-10.5 mmol L(-1) in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose

  5. Glucose-independent inhibition of yeast plasma-membrane H+-ATPase by calmodulin antagonists.

    PubMed Central

    Romero, I; Maldonado, A M; Eraso, P

    1997-01-01

    Glucose metabolism causes activation of the yeast plasma-membrane H+-ATPase. The molecular mechanism of this regulation is not known, but it is probably mediated by phosphorylation of the enzyme. The involvement in this process of several kinases has been suggested but their actual role has not been proved. The physiological role of a calmodulin-dependent protein kinase in glucose-induced activation was investigated by studying the effect of specific calmodulin antagonists on the glucose-induced ATPase kinetic changes in wild-type and two mutant strains affected in the glucose regulation of the enzyme. Preincubation of the cells with calmidazolium or compound 48/80 impeded the increase in ATPase activity by reducing the Vmax of the enzyme without modifying the apparent affinity for ATP in the three strains. In one mutant, pma1-T912A, the putative calmodulin-dependent protein kinase-phosphorylatable Thr-912 was eliminated, and in the other, pma1-P536L, H+-ATPase was constitutively activated, suggesting that the antagonistic effect was not mediated by a calmodulin-dependent protein kinase and not related to glucose regulation. This was corroborated when the in vitro effect of the calmodulin antagonists on H+-ATPase activity was tested. Purified plasma membranes from glucose-starved or glucose-fermenting cells from both pma1-P890X, another constitutively activated ATPase mutant, and wild-type strains were preincubated with calmidazolium or melittin. In all cases, ATP hydrolysis was inhibited with an IC50 of approximately 1 microM. This inhibition was reversed by calmodulin. Analysis of the calmodulin-binding protein pattern in the plasma-membrane fraction eliminates ATPase as the calmodulin target protein. We conclude that H+-ATPase inhibition by calmodulin antagonists is mediated by an as yet unidentified calmodulin-dependent membrane protein. PMID:9148755

  6. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

    PubMed Central

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G. P.; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J.; la Fleur, Susanne E.

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients. PMID:24339800

  7. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats.

    PubMed

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G P; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J; la Fleur, Susanne E

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients. PMID:24339800

  8. Caffeic acid as active principle from the fruit of Xanthium strumarium to lower plasma glucose in diabetic rats.

    PubMed

    Hsu, F L; Chen, Y C; Cheng, J T

    2000-04-01

    The antihyperglycemic effect of caffeic acid, one of the phenolic compounds contained in the fruit of Xanthium strumarium, was investigated. After an intravenous injection of caffeic acid into diabetic rats of both streptozotocin-induced and insulin-resistant models, a dose-dependent decrease of plasma glucose was observed. However, a similar effect was not produced in normal rats. An insulin-independent action of caffeic acid can thus be considered. Otherwise, this compound reduced the elevation of plasma glucose level in insulin-resistant rats receiving a glucose challenge test. Also, glucose uptake into the isolated adipocytes was raised by caffeic acid in a concentration-dependent manner. Increase of glucose utilization by caffeic acid seems to be responsible for the lowering of plasma glucose. PMID:10821047

  9. Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

    SciTech Connect

    Jacobs, D.B.; Berenski, C.J.; Spangler, R.A.; Jung, C.Y.

    1987-06-15

    The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size.

  10. The effect of insulin on plasma glucose concentrations, expression of hepatic glucose transporters and key gluconeogenic enzymes during the perinatal period in broiler chickens.

    PubMed

    Franssens, Lies; Lesuisse, Jens; Wang, Yufeng; Willems, Els; Willemsen, Hilke; Koppenol, Astrid; Guo, Xiaoquan; Buyse, Johan; Decuypere, Eddy; Everaert, Nadia

    2016-06-01

    Chickens have blood glucose concentrations that are twofold higher than those observed in mammals. Moreover, the insulin sensitivity seems to decrease with postnatal age in both broiler and layer chickens. However, little is known about the response of insulin on plasma glucose concentrations and mRNA abundance of hepatic glucose transporters 1, 2, 3, 8, 9 and 12 (GLUT1, 2, 3, 8, 9 and 12) and three regulatory enzymes of the gluconeogenesis, phosphoenolpyruvate carboxykinase 1 and 2 (PCK1 and 2) or fructose-1,6-biphosphatase 1 (FBP1) in chicks during the perinatal period. In the present study, broiler embryos on embryonic day (ED)16, ED18 or newly-hatched broiler chicks were injected intravenously with bovine insulin (1μg/g body weight (BW)) to examine plasma glucose response and changes in hepatic mRNA abundance of the GLUTs, PCK1 and 2 and FBP1. Results were compared with a non-treated control group and a saline-injected sham group. Plasma glucose levels of insulin-treated ED18 embryos recovered faster from their minimum level than those of insulin-treated ED16 embryos or newly-hatched chicks. In addition, at the minimum plasma glucose level seven hours post-injection (PI), hepatic GLUT2, FBP1 and PCK2 mRNA abundance was decreased in insulin-injected embryos, compared to sham and control groups, being most pronounced when insulin injection occurred on ED16. PMID:26723190

  11. Noninvasive measurement of plasma glucose from exhaled breath in healthy and type 1 diabetic subjects

    PubMed Central

    Oliver, Stacy R.; Ngo, Jerry; Flores, Rebecca; Midyett, Jason; Meinardi, Simone; Carlson, Matthew K.; Rowland, F. Sherwood; Blake, Donald R.; Galassetti, Pietro R.

    2011-01-01

    Effective management of diabetes mellitus, affecting tens of millions of patients, requires frequent assessment of plasma glucose. Patient compliance for sufficient testing is often reduced by the unpleasantness of current methodologies, which require blood samples and often cause pain and skin callusing. We propose that the analysis of volatile organic compounds (VOCs) in exhaled breath can be used as a novel, alternative, noninvasive means to monitor glycemia in these patients. Seventeen healthy (9 females and 8 males, 28.0 ± 1.0 yr) and eight type 1 diabetic (T1DM) volunteers (5 females and 3 males, 25.8 ± 1.7 yr) were enrolled in a 240-min triphasic intravenous dextrose infusion protocol (baseline, hyperglycemia, euglycemia-hyperinsulinemia). In T1DM patients, insulin was also administered (using differing protocols on 2 repeated visits to separate the effects of insulinemia on breath composition). Exhaled breath and room air samples were collected at 12 time points, and concentrations of ∼100 VOCs were determined by gas chromatography and matched with direct plasma glucose measurements. Standard least squares regression was used on several subsets of exhaled gases to generate multilinear models to predict plasma glucose for each subject. Plasma glucose estimates based on two groups of four gases each (cluster A: acetone, methyl nitrate, ethanol, and ethyl benzene; cluster B: 2-pentyl nitrate, propane, methanol, and acetone) displayed very strong correlations with glucose concentrations (0.883 and 0.869 for clusters A and B, respectively) across nearly 300 measurements. Our study demonstrates the feasibility to accurately predict glycemia through exhaled breath analysis over a broad range of clinically relevant concentrations in both healthy and T1DM subjects. PMID:21467303

  12. Associations between plasma glucose and DSM-III-R cluster B personality traits in psychiatric outpatients.

    PubMed

    Svanborg, P; Mattila-Evenden, M; Gustavsson, P J; Uvnäs-Moberg, K; Asberg, M

    2000-01-01

    Associations between personality traits, measured with the Karolinska Scales of Personality, the Impulsiveness subscale from the Impulsiveness, Venturesomeness and Empathy (IVE) Inventory, and with self-assessed personality traits and disorders (SCID-II Screen Questionnaire), and plasma insulin, glucagon and glucose, respectively, were explored in a sample of 101 psychiatric outpatients of both sexes. No relationships between the peptide hormones and personality measures were found. However, fasting glucose values, which were all essentially within the normal biological variation, were significantly related to several personality measures. For males, a low blood glucose was associated with low stable general level of functioning, with high IVE Impulsiveness, and with self-assessed histrionic and narcissistic traits. High number of self-assessed personality traits for all cluster B personality disorders was strongly associated with high IVE Impulsiveness. The results of the present study support the generalizability of earlier findings from alcoholic impulsive offenders: in males, low blood glucose is associated with an extrovert and impulsive, acting-out behavior that includes the breaking of societal norms and rules. In contrast, for females a positive relationship between fasting glucose and self-assessed histrionic personality traits was found. Because no association between global level of functioning and glucose was found in women, these personality traits may not necessarily be maladaptive, as was the case for males. PMID:10644928

  13. The validation of the Z-Scan technique for the determination of plasma glucose

    NASA Astrophysics Data System (ADS)

    Alves, Sarah I.; Silva, Elaine A. O.; Costa, Simone S.; Sonego, Denise R. N.; Hallack, Maira L.; Coppini, Ornela L.; Rowies, Fernanda; Azzalis, Ligia A.; Junqueira, Virginia B. C.; Pereira, Edimar C.; Rocha, Katya C.; Fonseca, Fernando L. A.

    2013-11-01

    Glucose is the main energy source for the human body. The concentration of blood glucose is regulated by several hormones including both antagonists: insulin and glucagon. The quantification of glucose in the blood is used for diagnosing metabolic disorders of carbohydrates, such as diabetes, idiopathic hypoglycemia and pancreatic diseases. Currently, the methodology used for this determination is the enzymatic colorimetric with spectrophotometric. This study aimed to validate the use of measurements of nonlinear optical properties of plasma glucose via the Z-Scan technique. For this we used samples of calibrator patterns that simulate commercial samples of patients (ELITech ©). Besides calibrators, serum glucose levels within acceptable reference values (normal control serum - Brazilian Society of Clinical Pathology and Laboratory Medicine) and also overestimated (pathological control serum - Brazilian Society of Clinical Pathology and Laboratory Medicine) were used in the methodology proposal. Calibrator dilutions were performed and determined by the Z-Scan technique for the preparation of calibration curve. In conclusion, Z-Scan method can be used to determinate glucose levels in biological samples with enzymatic colorimetric reaction and also to apply the same quality control parameters used in biochemistry clinical.

  14. Phospholipids from herring roe improve plasma lipids and glucose tolerance in healthy, young adults

    PubMed Central

    2014-01-01

    Background Herring roe is an underutilized source of n-3 polyunsaturated fatty acids (PUFAs) for human consumption with high phospholipid (PL) content. Studies have shown that PL may improve bioavailability of n-3 PUFAs. Arctic Nutrition’s herring roe product MOPL™30 is a PL: docosahexaenoic acid (DHA)-rich fish oil mixture, with a DHA:eicosapentaenoic acid (EPA) ratio of about 3:1, which is also rich in choline. In this pilot study, we determined if MOPL30 could favorably affect plasma lipid parameters and glucose tolerance in healthy young adults. Methods Twenty female and one male adults, between 22 and 26 years of age, participated in the study. Participants took encapsulated MOPL30, 2.4 g/d EPA + DHA, for 14 days, and completed a three-day weighed food record before and during the capsule intake. Plasma lipids and their fatty acid (FA) composition, plasma and red blood cell (RBC) phosphatidylcholine (PC) FA composition, acylcarnitines, choline, betaine and insulin were measured before and after supplementation (n = 21), and one and four weeks after discontinuation of supplementation (n = 14). An oral glucose tolerance test was performed before and after supplementation. Results Fasting plasma triacylglycerol and non-esterified fatty acids decreased and HDL-cholesterol increased after 14 days of MOPL30 intake (p < 0.05). The dietary records showed that PUFA intake prior to and during capsule intake was not different. Fasting plasma glucose was unchanged from before to after supplementation. However, during oral glucose tolerance testing, blood glucose at both 10 and 120 min was significantly lower after supplementation with MOPL30 compared to baseline measurements. Plasma free choline and betaine were increased, and the n-6/n-3 polyunsaturated (PUFA) ratio in plasma and RBC PC were decreased post-supplementation. Four weeks after discontinuation of MOPL30, most parameters had returned to baseline, but a delayed effect was observed on n-6

  15. Spectral analysis of time functions of plasma glucose and immunoreactive insulin during intravenous glucose tolerance testing on atherosclerosis and noninsulin-dependent diabetes mellitus

    NASA Astrophysics Data System (ADS)

    Malinov, Igor A.; Denisova, Tatyana P.; Malinova, Lidia I.; Brook, Sergey B.

    2000-04-01

    The time functions of plasma glucose and insulin obtained during intravenous glucose tolerance test were approximated by sections of Fourier series. The convincing quantitative and quality distinctions of amplitudes both phases of the first and second harmonics of decomposition of the indicated time functions are obtained. These distinctions were used as a basis of diagnostic algorithm of metabolic violations appropriate for atherosclerosis and non-insulin dependent diabetes mellitus in clinically obvious and preclinical stages.

  16. Investigation of relative metabolic changes in the organs and plasma of rats exposed to X-ray radiation using HR-MAS (1) H NMR and solution (1) H NMR.

    PubMed

    Jang, Won Gyo; Park, Ju Yeon; Lee, Jueun; Bang, Eunjung; Kim, So Ra; Lee, Eun Kyeong; Yun, Hyun Jin; Kang, Chang-Mo; Hwang, Geum-Sook

    2016-04-01

    Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ-specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high-resolution magic-angle-spinning (HR-MAS) NMR and solution NMR-based metabolic profiling were used to investigate dose-dependent metabolic changes in multiple organs and tissues - including the jejunum, spleen, liver, and plasma - of rats exposed to X-ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low-dose (2 Gy) and high-dose (6 Gy) X-ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high-dose compared with the low-dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post-irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X-ray radiation. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26871685

  17. Berries modify the postprandial plasma glucose response to sucrose in healthy subjects.

    PubMed

    Törrönen, Riitta; Sarkkinen, Essi; Tapola, Niina; Hautaniemi, Elina; Kilpi, Kyllikki; Niskanen, Leo

    2010-04-01

    Sucrose increases postprandial blood glucose concentrations, and diets with a high glycaemic response may be associated with increased risk of obesity, type 2 diabetes and CVD. Previous studies have suggested that polyphenols may influence carbohydrate digestion and absorption and thereby postprandial glycaemia. Berries are rich sources of various polyphenols and berry products are typically consumed with sucrose. We investigated the glycaemic effect of a berry purée made of bilberries, blackcurrants, cranberries and strawberries, and sweetened with sucrose, in comparison to sucrose with adjustment of available carbohydrates. A total of twelve healthy subjects (eleven women and one man, aged 25-69 years) with normal fasting plasma glucose ingested 150 g of the berry purée with 35 g sucrose or a control sucrose load in a randomised, controlled cross-over design. After consumption of the berry meal, the plasma glucose concentrations were significantly lower at 15 and 30 min (P < 0.05, P < 0.01, respectively) and significantly higher at 150 min (P < 0.05) compared with the control meal. The peak glucose concentration was reached at 45 min after the berry meal and at 30 min after the control meal. The peak increase from the baseline was 1.0 mmol/l smaller (P = 0.002) after ingestion of the berry meal. There was no statistically significant difference in the 3 h area under the glucose response curve. These results show that berries rich in polyphenols decrease the postprandial glucose response of sucrose in healthy subjects. The delayed and attenuated glycaemic response indicates reduced digestion and/or absorption of sucrose from the berry meal. PMID:19930765

  18. Effects of sauna and glucose intake on TSH and thyroid hormone levels in plasma of euthyroid subjects.

    PubMed

    Strbák, V; Tatár, P; Angyal, R; Strec, V; Aksamitová, K; Vigas, M; Jánosová, H

    1987-05-01

    The effect of sauna on thyroid function parameters and its modification by glucose was studied in young euthyroid male volunteers. A 30-minute stay in sauna resulted in an increase in plasma TSH; the response was exaggerated if glycemia had been increased by oral glucose intake at the beginning of the experiment. Plasma rT3 also increased in sauna, this response was, however, blunted by the higher glycemia. TSH response to sauna was definitely present in young men (aged 20 to 25) and absent in middle-aged ones (50 to 55). To explore the mechanism of the effect of increased glycemia, TRH tests were performed and dopamine infusions were administered with and without glucose pretreatment. Increased glycemia did not affect TSH and T3 response to TRH in young volunteers; however, 90 minutes after the administration, plasma rT3 levels were significantly lower in glucose pretreated subjects than in those receiving TRH injections after water pretreatment. Simultaneous infusion of glucose prevented the inhibitory effect of dopamine infusion on plasma TSH. It was concluded that glucose directly modulates the effect of sauna on plasma TSH at a suprapituitary level, while the inhibiting effect of glucose on plasma rT3 response to sauna and TRH is probably mediated by the insulin effect on thyroid hormone metabolism. PMID:3106755

  19. Alteration in plasma glucose levels in Japanese encephalitis patients.

    PubMed

    Tandon, Apurva; Singh, Aditi; Atrishi, Ekta; Saxena, S K; Mathur, Asha

    2002-02-01

    A unique factor, human T cell hypoglycaemic factor (hTCHF), has been shown to produce hypoglycaemia during the convalescent stage in the plasma of patients with Japanese encephalitis virus (JEV) infection. The present study was undertaken to investigate the ability of T cells from fresh peripheral blood mononuclear cells (PBMC) of such patients to produce hTCHF. The PBMC, as well as the individual subpopulations, were cultured for 24 h and the culture supernatants (CS) were assayed for hypoglycaemic activity. The activity was observed in the CD8+ T cells. The hypoglycaemia in JE-confirmed patients coincided with the gradual rise in circulating glucagon level, with no significant alterations in insulin, growth hormone and cortisol levels. The hTCHF was purified by ion exchange chromatography and the purified protein was observed as a approximately 25 kDa band on SDS-PAGE. Secretory hTCHF in the sera of patients and T cell CS was present in 88% of convalescent serum samples. We conclude that during the convalescent stage of JEV infection, a unique factor, hTCHF, is secreted by activated CD8+ T cells from patients and that this is responsible for the development of hypoglycaemia. PMID:12059908

  20. Postnatal Stress in Mice: Effects on Body Fat, Plasma Lipids, Glucose and Insulin.

    PubMed

    d'Amore, A; Caiola, S; Maroccia, E; Loizzo, A

    2000-01-01

    Mice pups were exposed to stressful stimuli everyday during the first 3 weeks of life. Body weight, food intake and spontaneous locomotor activity, triglycerides, cholesterol, phospholipids, glucose and insulin basal levels, as well as epididymal fat pad weight and its cell volume were measured in stressed and control animals. Results indicated that postnatal stressful manipulations induced an increase in body weight, epididymal fat pad weight and its cell volume, as well as in insulin, glucose, cholesterol and triglycerides plasma levels, at 4 months of age. No significant changes in food consumption, locomotor activity and phospholipids plasma levels were found. Present data suggest that early stressful manipulations may induce residual effects on lipid and glucid metabolism. PMID:27414054

  1. Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats.

    PubMed

    Legette, Leecole L; Luna, Arlyn Y Moreno; Reed, Ralph L; Miranda, Cristobal L; Bobe, Gerd; Proteau, Rosita R; Stevens, Jan F

    2013-07-01

    Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (p<0.05) elevated in the highest dose group. There was a dose-dependent effect on body weight and plasma glucose levels. The highest dose group (n=6) had significantly lower plasma glucose levels compared to the control group (n=6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome. PMID:22640929

  2. Diurnal Variation in Oral Glucose Tolerance: Blood Sugar and Plasma Insulin Levels Morning, Afternoon, and Evening

    PubMed Central

    Jarrett, R. J.; Baker, I. A.; Keen, H.; Oakley, N. W.

    1972-01-01

    Twenty-four subjects received three oral glucose tolerance tests, in the morning, afternoon, and evening of separate days. The mean blood sugar levels in the afternoon and evening tests were similar, and they were both significantly higher than those in the morning test. Plasma immunoreactive insulin levels, however, were highest in the morning test. The pattern of insulin levels during the afternoon and evening tests resembled that described as typical of maturity-onset diabetes. PMID:5058728

  3. Risk Factors and Plasma Glucose Profile of Gestational Diabetes in Omani Women

    PubMed Central

    Chitme, Havagiray R; Al Shibli, Sumaiya Abdallah Said; Al-Shamiry, Raya Mahmood

    2016-01-01

    Objectives We sought to conduct a detailed study on the risk factors of gestational diabetes mellitus (GDM) in Omani women to determine the actual and applicable risk factors and glucose profile in this population. Methods We conducted a cross-sectional case-control study using pregnant women diagnosed with GDM. Pregnant women without GDM were used as a control group. We collected information related to age, family history, prior history of pregnancy complications, age of marriage, age of first pregnancy, fasting glucose level, and oral glucose tolerance test (OGTT) results from three hospitals in Oman through face-to-face interviews and hospital records. Results The median age of women with GDM was 33 years old (p < 0.050). A significant risk was noted in women with a history of diabetes (p < 0.001), and those with mothers’ with a history of GDM. A significant (p < 0.010) relationship with a likelihood ratio of 43.9 was observed between the incidence of GDM in women with five or six pregnancies, a history of > 3 deliveries, height < 155 cm, and pregnancy or marriage at age < 18 years (p < 0.010). The mean difference in random plasma glucose, one-hour OGTT, and two-hour OGTT was significantly higher in GDM cases compared to control. Conclusions Glucose profile, family history, anthropometric profile, and age of first pregnancy and marriage should be considered while screening for GDM and determining the care needs of Omani women with GDM. PMID:27602192

  4. The effect of portal infusions of epinephrine on ingestion, plasma glucose and insulin in dogs.

    PubMed

    Bellinger, L L; Williams, F E

    1990-09-01

    Preabsorptive satiety has been hypothesized to occur as the result of food activating oral and gastrointestinal receptors that cause the release of catecholamines in the liver. The catecholamines were then proposed to hyperpolarize hepatic glucoreceptors and produce satiety. In the present study the hepatic portal vein was chronically cannulated in six mongrel dogs. Upon recovery the dogs were infused, over three minutes, with either saline or epinephrine (0.83 and 1.5 micrograms/kg b. wt.). Infusions ended 10 minutes prior to the animals' daily one-hour feeding period. The epinephrine infusions resulted in physiological increases in plasma glucose and insulin, but did not inhibit food consumption. The animals were next prefed 20% of their normal daily food intake 30 minutes prior to infusion of epinephrine at the above noted doses. Again plasma glucose and insulin increased, but food consumption was not affected. These data show that epinephrine infusions which produce physiological changes in plasma glucose and insulin do not alter feeding behavior of mongrel dogs. These findings are in agreement with previous data that question the physiological importance of the preabsorptive catecholamine satiety hypothesis. PMID:2176295

  5. Mediation of Endogenous β-endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin-induced Diabetic Rats

    PubMed Central

    2004-01-01

    The role of β-endorphin in the plasma glucose-lowering action of tetrandrine in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. The plasma glucose concentration was assessed by the glucose oxidase method. The enzyme-linked immunosorbent assay was used to determine the plasma level of β-endorphin-like immunoreactivity (BER). The mRNA levels of glucose transporter subtype 4 (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats were detected by Northern blotting analysis. The expressed protein of GLUT4 or PEPCK was characterized by Western blotting analysis. Tetrandrine dose-dependently increased plasma BER in a manner parallel to the decrease of plasma glucose in STZ-diabetic rats. Moreover, the plasma glucose-lowering effect of tetrandrine was inhibited by naloxone and naloxonazine at doses sufficient to block opioid μ-receptors. Further, tetrandrine failed to produce plasma glucose-lowering action in opioid μ-receptor knockout diabetic mice. Bilateral adrenalectomy eliminated the plasma glucose-lowering effect and plasma BER-elevating effect of tetrandrine in STZ-diabetic rats. Both effects were abolished by treatment with hexamethonium or pentolinium at doses sufficient to block nicotinic receptors. Tetrandrine enhanced BER release directly from the isolated adrenal medulla of STZ-diabetic rats and this action was abolished by the blockade of nicotinic receptors. Repeated intravenous administration of tetrandrine (1.0 mg/kg) to STZ-diabetic rats for 3 days resulted in an increase in the mRNA and protein levels of the GLUT4 in soleus muscle, in addition to the lowering of plasma glucose. Similar treatment with tetrandrine reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. The obtained results suggest that tetrandrine may induce the activation of nicotinic receptors in adrenal medulla to enhance the secretion of β-endorphin, which could

  6. Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species-induced insulin resistance in mice.

    PubMed

    Hu, Hailong; Guo, Qian; Wang, Changlin; Ma, Xiao; He, Hongjuan; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2015-10-01

    There have been few reports about the possible toxic effects of titanium dioxide (TiO2 ) nanoparticles on the endocrine system. We explored the endocrine effects of oral administration to mice of anatase TiO2 nanoparticles (0, 64 and 320 mg kg(-1) body weight per day to control, low-dose and high-dose groups, respectively, 7 days per week for 14 weeks). TiO2 nanoparticles were characterized by scanning and transmission electron microscopy (TEM) and dynamic light scattering (DLS), and their physiological distribution was investigated by inductively coupled plasma. Biochemical analyzes included plasma glucose, insulin, heart blood triglycerides (TG), free fatty acid (FFA), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and reactive oxygen species (ROS)-related markers (total SOD, GSH and MDA). Phosphorylation of IRS1, Akt, JNK1, and p38 MAPK were analyzed by western blotting. Increased titanium levels were found in the liver, spleen, small intestine, kidney and pancreas. Biochemical analyzes showed that plasma glucose significantly increased whereas there was no difference in plasma insulin secretion. Increased ROS levels were found in serum and the liver, as evidenced by reduced total SOD activity and GSH level and increased MDA content. Western blotting showed that oral administration of TiO2 nanoparticles induced insulin resistance (IR) in mouse liver, shown by increased phosphorylation of IRS1 (Ser307) and reduced phosphorylation of Akt (Ser473). The pathway by which TiO2 nanoparticles increase ROS-induced IR were included in the inflammatory response and phosphokinase, as shown by increased serum levels of TNF-α and IL-6 and increased phosphorylation of JNK1 and p38 MAPK in liver. These results show that oral administration of TiO2 nanoparticles increases ROS, resulting in IR and increasing plasma glucose in mice. PMID:25826740

  7. Mediation of beta-endorphin by isoferulic acid to lower plasma glucose in streptozotocin-induced diabetic rats.

    PubMed

    Liu, I-Min; Chen, Wang-Chuan; Cheng, Juei-Tang

    2003-12-01

    We investigated the mechanism(s) by which isoferulic acid lowers plasma glucose levels in streptozotocin-induced diabetic rats (STZ-diabetic rats). In STZ-diabetic rats, isoferulic acid dose dependently lowered plasma glucose concentrations and increased plasma beta-endorphin-like immunoreactivity (BER). Both of these effects of isoferulic acid were abolished by pretreatment of rats with tamsulosin or 2-[2,6-dimethoxyphenoxyethyl]aminomethyl-1,4-benzodioxane hydrochloride (WB 4101) at doses sufficient to block alpha1-adrenoceptors. Also, isoferulic acid enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that could be abolished by treatment with alpha1-adrenoceptor antagonists. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of isoferulic acid, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Naloxone and naloxonazine inhibited the plasma glucose-lowering activity of isoferulic acid at doses sufficient to block opioid mu-receptors. In contrast with the effect in wild-type diabetic mice, isoferulic acid failed to lower plasma glucose levels in opioid mu-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with isoferulic acid three times in 1 day resulted in an increase in the expression of the glucose transporter subtype 4 form in soleus muscle. This effect was blocked by alpha1-adrenoceptor or opioid mu-receptor antagonists. The reduction of elevated mRNA or protein level of hepatic phosphoenolpyruvate carboxykinase was also impeded in the same groups of STZ-diabetic rats. In conclusion, our results suggest that isoferulic acid may activate alpha1-adrenoceptors to enhance the secretion of beta-endorphin, which can stimulate the opioid mu-receptors to increase glucose use or/and reduce hepatic gluconeogenesis, resulting in a decrease of plasma glucose in STZ-diabetic rats. PMID:12975496

  8. Circadian Control of the Daily Plasma Glucose Rhythm: An Interplay of GABA and Glutamate

    PubMed Central

    Kalsbeek, Andries; Foppen, Ewout; Schalij, Ingrid; Van Heijningen, Caroline; van der Vliet, Jan; Fliers, Eric; Buijs, Ruud M.

    2008-01-01

    The mammalian biological clock, located in the hypothalamic suprachiasmatic nuclei (SCN), imposes its temporal structure on the organism via neural and endocrine outputs. To further investigate SCN control of the autonomic nervous system we focused in the present study on the daily rhythm in plasma glucose concentrations. The hypothalamic paraventricular nucleus (PVN) is an important target area of biological clock output and harbors the pre-autonomic neurons that control peripheral sympathetic and parasympathetic activity. Using local administration of GABA and glutamate receptor (ant)agonists in the PVN at different times of the light/dark-cycle we investigated whether daily changes in the activity of autonomic nervous system contribute to the control of plasma glucose and plasma insulin concentrations. Activation of neuronal activity in the PVN of non-feeding animals, either by administering a glutamatergic agonist or a GABAergic antagonist, induced hyperglycemia. The effect of the GABA-antagonist was time dependent, causing increased plasma glucose concentrations only when administered during the light period. The absence of a hyperglycemic effect of the GABA-antagonist in SCN-ablated animals provided further evidence for a daily change in GABAergic input from the SCN to the PVN. On the other hand, feeding-induced plasma glucose and insulin responses were suppressed by inhibition of PVN neuronal activity only during the dark period. These results indicate that the pre-autonomic neurons in the PVN are controlled by an interplay of inhibitory and excitatory inputs. Liver-dedicated sympathetic pre-autonomic neurons (responsible for hepatic glucose production) and pancreas-dedicated pre-autonomic parasympathetic neurons (responsible for insulin release) are controlled by inhibitory GABAergic contacts that are mainly active during the light period. Both sympathetic and parasympathetic pre-autonomic PVN neurons also receive excitatory inputs, either from the

  9. The effects of post-exercise glucose and alanine ingestion on plasma carnitine and ketosis in humans.

    PubMed Central

    Carlin, J I; Olson, E B; Peters, H A; Reddan, W G

    1987-01-01

    1. Several studies have hypothesized that alanine decreases plasma ketone body levels by increasing availability of oxaloacetate, thus allowing acetyl groups to enter the tricarboxylic acid cycle and releasing co-enzyme A (CoA). 2. Four, fasted adult males exercised at 50% of their maximal oxygen consumption for 1.5 h, then ingested 100 g of either glucose or alanine 2 h into recovery. 3. Post-exercise ketosis had developed at 2 h into recovery, as shown by a significantly elevated concentration of beta-hydroxybutyrate in the plasma. At this time plasma free fatty acids were elevated above resting levels while plasma free carnitine concentrations had fallen below resting values. 4. After either alanine or glucose ingestion beta-hydroxybutyrate concentrations fell to the same extent. After the alanine load free carnitine increased above that seen in the glucose trial. Following either alanine or glucose ingestion free fatty acid levels fell; they remained at resting levels in the alanine trial but decreased below rest in the glucose trial. 5. We assume that plasma carnitine concentrations largely reflect the hepatic carnitine pools; therefore, elevations in the plasma free carnitine are probably the result of an increased utilization of acetyl CoA. The significant elevation in plasma free carnitine concentration found after alanine ingestion is consistent with the hypothesis that alanine increases the oxidation of acetyl CoA by providing oxaloacetate for the tricarboxylic acid cycle. PMID:3443938

  10. Effect of quinine therapy on plasma glucose and plasma insulin levels in pregnant women infected with Plasmodium falciparum malaria in Gezira state.

    PubMed

    Elbadawi, N E E; Mohamed, M I; Dawod, O Y; Ali, K E; Daoud, O H; Ali, E M; Ahmed, E G E; Mohamed, A E

    2011-09-01

    To determine if quinine has a metabolic effect during treatment of severe or complicated malaria, we studied its effects on plasma glucose and plasma insulin levels in 150 pregnant women with malaria referred to Madani maternity teaching hospital, Gezira state and 50 healthy pregnant controls. Levels were determined at baseline (day 0) before the start of quinine treatment, after 2 days of treatment (2 hours after the 4th dose) and after 7 days of treatment (day 8). There was a statistically significant increase in plasma insulin concentrations during the quinine infusion and fall in plasma glucose concentration (P < 0.001). Quinine administered at the recommended dose and rate can disrupt plasma glucose homeostasis although it is still the drug of choice for severe and complicated malaria in Sudan. PMID:22259921

  11. Reciprocal regulation of insulin and plasma 5'-AMP in glucose homeostasis in mice.

    PubMed

    Xia, Lin; Wang, Zhongqiu; Zhang, Ying; Yang, Xiao; Zhan, Yibei; Cheng, Rui; Wang, Shiming; Zhang, Jianfa

    2015-03-01

    A previous investigation has demonstrated that plasma 5'-AMP (pAMP) exacerbates and causes hyperglycemia in diabetic mice. However, the crosstalk between pAMP and insulin signaling to regulate glucose homeostasis has not been investigated in depth. In this study, we showed that the blood glucose level was more dependent on the ratio of insulin to pAMP than on the absolute level of these two factors. Administration of 5'-AMP significantly attenuated the insulin-stimulated insulin receptor (IR) autophosphorylation in the liver and muscle tissues, resulting in the inhibition of downstream AKT phosphorylation. A docking analysis indicated that adenosine was a potential inhibitor of IR tyrosine kinase. Moreover, the 5'-AMP treatment elevated the ATP level in the pancreas and in the isolated islets, stimulating insulin secretion and increasing the plasma level of insulin. The insulin administration decreased the 5'-AMP-induced hyper-adenosine level by the up-regulation of adenosine kinase activities. Our results indicate that blood glucose homeostasis is reciprocally regulated by pAMP and insulin. PMID:25512345

  12. Rice (Oryza sativa japonica) Albumin Suppresses the Elevation of Blood Glucose and Plasma Insulin Levels after Oral Glucose Loading.

    PubMed

    Ina, Shigenobu; Ninomiya, Kazumi; Mogi, Takashi; Hase, Ayumu; Ando, Toshiki; Matsukaze, Narumi; Ogihara, Jun; Akao, Makoto; Kumagai, Hitoshi; Kumagai, Hitomi

    2016-06-22

    The suppressive effect of rice albumin (RA) of 16 kDa on elevation of blood glucose level after oral loading of starch or glucose and its possible mechanism were examined. RA suppressed the increase in blood glucose levels in both the oral starch tolerance test and the oral glucose tolerance test. The blood glucose concentrations 15 min after the oral administration of starch were 144 ± 6 mg/dL for control group and 127 ± 4 mg/dL for RA 200 mg/kg BW group, while those after the oral administration of glucose were 157 ± 7 mg/dL for control group and 137 ± 4 mg/dL for RA 200 mg/kg BW group. However, in the intraperitoneal glucose tolerance test, no significant differences in blood glucose level were observed between RA and the control groups, indicating that RA suppresses the glucose absorption from the small intestine. However, RA did not inhibit the activity of mammalian α-amylase. RA was hydrolyzed to an indigestible high-molecular-weight peptide (HMP) of 14 kDa and low-molecular-weight peptides by pepsin and pancreatin. Furthermore, RA suppressed the glucose diffusion rate through a semipermeable membrane like dietary fibers in vitro. Therefore, the indigestible HMP may adsorb glucose and suppress its absorption from the small intestine. PMID:27228466

  13. Higher Fasting Plasma Glucose Levels, within the Normal Range, are Associated with Decreased Processing Speed in High Functioning Young Elderly.

    PubMed

    Raizes, Meytal; Elkana, Odelia; Franko, Motty; Ravona Springer, Ramit; Segev, Shlomo; Beeri, Michal Schnaider

    2015-01-01

    We explored the association of plasma glucose levels within the normal range with processing speed in high functioning young elderly, free of type 2 diabetes mellitus (T2DM). A sample of 41 participants (mean age = 64.7, SD = 10; glucose 94.5 mg/dL, SD = 9.3), were examined with a computerized cognitive battery. Hierarchical linear regression analysis showed that higher plasma glucose levels, albeit within the normal range (<110 mg/dL), were associated with longer reaction times (p <  0.01). These findings suggest that even in the subclinical range and in the absence of T2DM, monitoring plasma glucose levels may have an impact on cognitive function. PMID:26484908

  14. Intravenous lipid and amino acids briskly increase plasma glucose concentrations in small premature infants.

    PubMed

    Savich, R D; Finley, S L; Ogata, E S

    1988-07-01

    We determined the glycemic response to intravenous lipid infusion alone, lipid with amino acids, or amino acids alone in 15 very small premature infants receiving constant glucose infusion during early life. Infants who received lipid or lipid and amino acids demonstrated significant increases in glucose compared with infants who received amino acids. The combination of lipid and amino acids resulted in an earlier increase than lipid alone. Although plasma insulin did not change in all three groups, infants who received amino acids alone demonstrated an appropriate increase in glucagon. These data suggest that lipid infusion, a commonly used means of providing nutrition to premature infants, may cause significant disturbances in glucoregulation, particularly when administered with amino acids. PMID:3132930

  15. Restoration of early rise in plasma insulin levels improves the glucose tolerance of type 2 diabetic patients.

    PubMed

    Bruttomesso, D; Pianta, A; Mari, A; Valerio, A; Marescotti, M C; Avogaro, A; Tiengo, A; Del Prato, S

    1999-01-01

    The loss of first-phase insulin secretion is a characteristic feature of type 2 diabetic patients. The fast-acting insulin analog lispro provides a therapeutic tool for assessing the metabolic outcome of restoration of an early rise in plasma insulin levels after the ingestion of an oral glucose load. We studied eight type 2 diabetic patients on two different occasions when they received an oral glucose load (50 g) preceded by either human regular insulin or insulin analog lispro (both 0.075 U/kg lean body mass). Tritiated glucose was infused throughout the studies, and the oral glucose was labeled with [13C6]glucose for monitoring systemic and oral glucose kinetics, respectively. Basal plasma glucose (8.2 +/- 0.9 vs. 7.5 +/- 0.8 mmol/l), insulin (224 +/- 21 vs. 203 +/- 21 pmol/l), and endogenous glucose production (10.4 +/- 1.0 vs. 11.1 +/- 1.1 micromol x kg(-1) x min(-1)) were similar on both occasions. In spite of comparable incremental areas under the curve, the time course of plasma insulin concentration was much different. After injection of regular insulin, plasma insulin peaked at 120 min (368 +/- 42 pmol/l), while with lispro, the peak occurred at 60 min (481 +/- 42 pmol/l). Plasma insulin concentration during the last 3 h of the study, however, was lower with lispro compared with regular insulin. The incremental area under the curve of plasma C-peptide was lower with lispro (0.05 +/- 0.01 vs. 0.13 +/- 0.04 micromol/300 min; P < 0.01). After the ingestion of the oral glucose load, plasma glucose concentration increased by 78% at 80-100 min with regular insulin and by 62% with lispro (P < 0.05) and remained lower for the ensuing 3 h. The incremental area under the curve was 46% lower with lispro (715 +/- 109 vs. 389 +/- 109 pmol/300 min; P < 0.01). There was no difference in the two studies in the rate of appearance of the ingested glucose and in the overall rate of glucose disposal. During the initial 90 min, however, the rate of endogenous glucose

  16. Effects of Chinese herbal medicine on plasma glucose, protein and energy metabolism in sheep

    PubMed Central

    2013-01-01

    Background The use of antibiotics in animal diets is facing negative feedback due to the hidden danger of drug residues to human health. Traditional Chinese herbal medicine has been used to replace antibiotics in the past two decades and played an increasingly important role in livestock production. The present study was carried out to assess the feeding effects of a traditional nourishing Chinese herbal medicine mixture on kinetics of plasma glucose, protein and energy metabolism in sheep. Ruminal fermentation characteristics were also determined. Methods Four sheep were fed on either mixed hay (MH-diet) or MH-diet supplemented with 2% of Chinese herbal medicine (mixture of Astragalus root, Angelica root and Atractylodes rhizome; CHM-diet) over two 35-day periods using a crossover design. The turnover rate of plasma glucose was measured with an isotope dilution method using [U-13C]glucose. The rates of plasma leucine turnover and leucine oxidation, whole body protein synthesis (WBPS) and metabolic heat production were measured using the [1-13C]leucine dilution and open circuit calorimetry. Results Body weight gain of sheep was higher (P = 0.03) for CHM-diet than for MH-diet. Rumen pH was lower (P = 0.02), concentration of rumen total volatile fatty acid tended to be higher (P = 0.05) and acetate was higher (P = 0.04) for CHM-diet than for MH-diet. Turnover rates of plasma glucose and leucine did not differ between diets. Oxidation rate of leucine tended to be higher (P = 0.06) for CHM-diet than for MH-diet, but the WBPS did not differ between diets. Metabolic heat production tended to be greater (P = 0.05) for CHM-diet than for MH-diet. Conclusions The sheep fed on CHM-diet had a higher body weight gain and showed positive impacts on rumen fermentation and energy metabolism without resulting in any adverse response. Therefore, these results suggested that the Chinese herbal medicine mixture should be considered as a potential feed additive

  17. Effects of Cr methionine on glucose metabolism, plasma metabolites, meat lipid peroxidation, and tissue chromium in Mahabadi goat kids.

    PubMed

    Emami, A; Ganjkhanlou, M; Zali, A

    2015-03-01

    This study was designed to investigate the effects of chromium methionine (Cr-Met) on glucose metabolism, blood metabolites, meat lipid peroxidation, and tissue chromium (Cr) in Mahabadi goat kids. Thirty-two male kids (16.5 ± 2.8 kg BW, 4-5 months of age) were fed for 90 days in a completely randomized design with four treatments. Treatments were supplemented with 0 (control), 0.5, 1, and 1.5 mg Cr as Cr-Met/animal/daily. Blood samples were collected via heparin tubes from the jugular vein on 0, 21, 42, 63, and 90 days of experiment. On day 70, an intravenous glucose tolerance test (IVGTT) was conducted. At the end of the feeding trial, the kids were slaughtered, and the liver, kidney, and longissimus dorsi (LD) muscle samples were collected. Plasma glucose, insulin, and triglyceride concentrations were decreased by Cr supplementation (P < 0.05). LD muscle malondialdehyde (MDA) decreased, and plasma and tissue Cr contents increased with increasing supplemental Cr levels (P < 0.05). Plasma glucose concentrations at 30 and 60 min after glucose infusion were lower in the kids fed 1.5 mg Cr diet than the kids fed control diet (P < 0.05). The IVGTT indicated that the kids supplemented with 1.5 mg Cr had higher glucose clearance rate (K) and lower glucose half-life (T½; P < 0.05). Glucose area under the response curve (AUC) from 0 to 180 min after glucose infusion was decreased linearly (P < 0.01) by supplemental Cr. The results suggested that supplemental Cr may improve glucose utilization and lipid oxidation of meat in fattening kid. PMID:25476000

  18. Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration.

    PubMed

    Knuth, Nicolas D; Shrivastava, Cara R; Horowitz, Jeffrey F

    2009-01-01

    The primary goal of this study was to determine the acute glycemic and endocrine responses to the reduction of fat content from a meal. On three separate occasions, nine overweight subjects (body mass index = 30 +/- 1 kg/m(2); 5 men, 4 women) consumed 1) a control meal ( approximately 800 kcal; 100 g of carbohydrate, 31 g of fat, and 30 g of protein), 2) a low-fat meal ( approximately 530 kcal; 100 g of carbohydrate, 1 g of fat, and 30 g of protein), or 3) a low-fat meal plus lipid infusion [same meal as low-fat meal, but the total energy provided was the same as control (800 kcal), with the "missing" fat ( approximately 30 g) provided via an intravenous lipid infusion]. All three meals contained [(13)C]glucose (3 mg/kg body wt) to assess the bioavailability of ingested glucose. During the 5-h period after each meal, we measured the recovery of [(13)C]glucose in plasma, plasma glucose, and insulin concentrations. We also measured plasma concentration of the gastrointestinal peptides: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY(3-36) (PYY(3-36)). The recovery of the ingested [(13)C]glucose in the hour after ingestion was greater (P < 0.05) after the low-fat than after the control meal [area under the curve (AUC): 1,206 +/- 252 and 687 +/- 161 microM.h, respectively]. However, removing dietary fat from the meal did not affect the plasma concentration of glucose or insulin. Importantly, [(13)C]glucose recovery was not different during the low-fat and lipid infusion trials (AUC: 1,206 +/- 252 and 1,134 +/- 247 microM.h, respectively), indicating that the accelerated delivery of exogenous glucose found after removing fat from the meal is due exclusively to the reduction of fat in the gastrointestinal tract. In parallel with these findings, the reduction in fat calories from the meal reduced plasma concentration of GIP, GLP-1, and PYY(3-36). In summary, these data suggest that removing fat from the diet expedited

  19. Postprandial plasma glucose effects of once-weekly albiglutide for the treatment of type 2 diabetes.

    PubMed

    Matthews, Jessica E; Reinhardt, Rickey R; Carr, Molly C

    2016-05-01

    Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) vary in their structure, duration of action, efficacy, and safety. In order to optimize glycemic control, it is important to target both fasting (FPG) and postprandial plasma (PPG) glucose. Although phase 3 trials document the effect of GLP-1 RAs on glycated hemoglobin, few data are available to assess their effect on PPG. Albiglutide is a once-weekly GLP-1 RA with a half-life of ≈ 5 days. The goal of this review is to summarize the effects of albiglutide on PPG in four phase 2 trials and to describe the PPG-lowering effects of the GLP-1 RAs. At clinically relevant doses (30-64 mg), albiglutide consistently lowered PPG after each meal in addition to its effect on lowering FPG. Multiple weekly subcutaneous injections of albiglutide led to improvements in a variety of glycemic measures, including maximal reductions in PPG from baseline, postmeal glucose excursions, and FPG. Albiglutide, a longer-acting GLP-1 RAs, provides reductions in FPG, PPG following meals, and glucose over 24 hours. PMID:27043162

  20. Plasma Levels of Glucose and Insulin in Patients with Brain Tumors

    PubMed Central

    ALEXANDRU, OANA; ENE, L.; PURCARU, OANA STEFANA; TACHE, DANIELA ELISE; POPESCU, ALISA; NEAMTU, OANA MARIA; TATARANU, LIGIA GABRIELA; GEORGESCU, ADA MARIA; TUDORICA, VALERICA; ZAHARIA, CORNELIA; DRICU, ANICA

    2014-01-01

    In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors. PMID:24791202

  1. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    PubMed

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes. PMID:25757438

  2. Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxyindoles.

    PubMed

    Yokogoshi, H; Roberts, C H; Caballero, B; Wurtman, R J

    1984-07-01

    Administration of the artificial sweetener aspartame (L-aspartylphenylalanylmethyl ester; 200 mg/kg) by gavage to rats caused large increments in brain and plasma levels of phenylalanine and its product tyrosine. Glucose administration (3 g/kg, by gavage, a dose sufficient to cause insulin-mediated reductions in plasma levels of the large neutral amino acids leucine, isoleucine, and valine) also elevated brain phenylalanine and tyrosine, and enhanced the increments caused by the aspartame, nearly doubling the rise in brain phenylalanine. Each animal's brain phenylalanine or tyrosine levels were highly correlated (r = 0.97 and 0.99, respectively) with its plasma phenylalanine or tyrosine ratios, affirming that aspartame's effects on the brain amino acids result from the changes it produces in plasma composition. As described previously, glucose consumption increased brain tryptophan levels, and consequently, brain levels of the 5-hydroxyindoles serotonin and 5-hydroxyindoleacetic acid. Aspartame alone had no effect on these compounds but completely blocked the changes in 5-hydroxyindoles caused by glucose. Each animal's brain level of tryptophan (r = 0.89) and 5-hydroxyindoles (r = 0.74) was also significantly correlated with its plasma tryptophan ratio, affirming that the effects of glucose or aspartame on these brain constituents also result from the changes they produce in plasma composition. The aspartame-glucose combination also reduced brain levels of leucine, isoleucine, and valine to a significantly greater extent than aspartame or glucose alone. These observations indicate that high aspartame doses can generate major neurochemical changes in rats, especially when consumed along with carbohydrate-containing foods. However, they should not in any way be interpreted as demonstrating that aspartame significantly affects the human brain. PMID:6204522

  3. Fasting plasma glucose 6–12 weeks after starting insulin glargine predicts likelihood of treatment success: a pooled analysis

    PubMed Central

    Karl, D; Zhou, R; Vlajnic, A; Riddle, M

    2012-01-01

    Aims To evaluate whether fasting plasma glucose values measured early during insulin therapy can identify patients with Type 2 diabetes who may not achieve adequate glycaemic control after 6 months and will require additional treatment. Methods Patient-level data from seven prospective, randomized, controlled studies using treat-to-target methods were pooled to evaluate the efficacy of insulin glargine. Fasting plasma glucose was measured at baseline, week 6 or 8 (6/8) and week 12. HbA1c was measured at week 24 to assess glycaemic control. Results One thousand and thirty-six patients (56% male, 81% white) were included in the analysis (mean age 56.3 years; duration of diabetes 8.4 years). Baseline mean fasting plasma glucose was 11.2 mmol/l and mean HbA1c was 73 mmol/mol (8.8%). After 24 weeks of treatment, mean HbA1c decreased to 53 mmol/mol (7.0%); 56% of patients reached a target HbA1c≤ 53 mmol/mol (7.0%). Significant correlations with week 24 HbA1c were obtained for fasting plasma glucose measured at week 6/8 and week 12 (r = 0.32; P < 0.0001 for both). Patients with fasting plasma glucose > 10 mmol/l at week 6/8 or week 12 were significantly less likely to achieve the HbA1c target at the end of treatment than patients with fasting plasma glucose < 8.9 mmol/l (P < 0.0001 for both). If fasting plasma glucose was > 10 mmol/l at week 6/8 or week 12, patients had only a 27% chance of reaching the HbA1c goal. Conclusions Fasting plasma glucose remaining > 10 mmol/l after 6–12 weeks of glargine therapy indicates that reaching target HbA1c≤ 53 mmol/mol (7.0%) is unlikely and calls for individualized attention to consider further therapeutic options. PMID:22413808

  4. Native fluorescence spectroscopy of blood plasma of rats with experimental diabetes: identifying fingerprints of glucose-related metabolic pathways

    NASA Astrophysics Data System (ADS)

    Shirshin, Evgeny; Cherkasova, Olga; Tikhonova, Tatiana; Berlovskaya, Elena; Priezzhev, Alexander; Fadeev, Victor

    2015-05-01

    We present the results of a native fluorescence spectroscopy study of blood plasma of rats with experimental diabetes. It was shown that the fluorescence emission band shape at 320 nm excitation is the most indicative of hyperglycemia in the blood plasma samples. We provide the interpretation of this fact based on the changes in reduced nicotinamide adenine dinucleotide phosphate concentration due to glucose-related metabolic pathways and protein fluorescent cross-linking formation following nonenzymatic glycation.

  5. Does sugar content matter? Blood plasma glucose levels in an occasional and a specialist avian nectarivore.

    PubMed

    Witteveen, Minke; Brown, Mark; Downs, Colleen T

    2014-01-01

    Nectar composition within a plant pollinator group can be variable, and bird pollinated plants can be segregated into two groups based on their adaptations to either a specialist or an occasional bird pollination system. Specialist nectarivores rely primarily on nectar for their energy requirements, while occasional nectarivores meet their energy requirements from nectar as well as from seeds, fruit and insects. Avian blood plasma glucose concentration (PGlu) is generally high compared with mammals. It is also affected by a range of factors including species, gender, age, ambient temperature, feeding pattern, reproductive status, circadian rhythm and moult status, among others. We examined whether sugar content affected PGlu of two avian nectarivores, a specialist nectarivore the Amethyst Sunbird Chalcomitra amethystina, and an occasional nectarivore the Cape White-eye Zosterops virens, when fed sucrose-hexose sugar solution diets of varying concentrations (5%-35%). Both species regulated PGlu within a range which was affected by sampling time (fed or fasted) and not dietary sugar concentration. The range in mean PGlu was broader in Amethyst Sunbirds (11.52-16.51mmol/L) compared with Cape White-eyes (14.33-15.85mmol/L). This suggests that these birds are not constrained by dietary sugar concentration with regard to PGlu regulation, and consequently selective pressure on plants for their nectar characteristics is due to reasons other than glucose regulation. PMID:24095723

  6. Amperometric biosensor based on glucose dehydrogenase and plasma-polymerized thin films.

    PubMed

    Hiratsuka, Atsunori; Fujisawa, Kohta; Muguruma, Hitoshi

    2008-04-01

    A novel design is described for an amperometric biosensor based on NAD(P)-dependent glucose dehydrogenase (GDH) combined with a plasma-polymerized thin film (PPF). The GDH is sandwiched between several nanometer thick acetonitrile PPFs on a sputtered gold electrode (PPF/GDH/PPF/Au). The lower PPF layer plays the role as an interface between enzyme and electrode because it is extremely thin, adheres well to the substrate (electrode), has a flat surface and a highly-crosslinked network structure, and is hydrophilic in nature. The upper PPF layer (overcoating) was directly deposited on immobilized GDH. The optimized amperometric biosensor characteristics covered 2.5-26 mM glucose concentration at +0.6 V of applied potential; the least-squares slope was 320 nA mM(-1) cm(-2) and the correlation coefficient was 0.990. Unlike conventional wet-chemical processes that are incompatible with mass production techniques, this dry-chemistry procedure has great potential for enabling high-throughput production of bioelectronic devices. PMID:18403839

  7. Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study

    PubMed Central

    Yuan, Hai-Yan; Liang, Hai-Xia; Liang, Guang-Rong; Zhang, Gui-Xiang; Li, Huan-De

    2008-01-01

    Background: Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine. Objective: The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice. Methods: C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29. Results: Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] μIU/mL; P < 0.05) and

  8. Relationship Between A1C and Fasting Plasma Glucose in Dysglycemia or Type 2 Diabetes

    PubMed Central

    Ramachandran, Ambady; Riddle, Matthew C.; Kabali, Conrad; Gerstein, Hertzel C.

    2012-01-01

    OBJECTIVE A1C measurement has advantages over measures of plasma glucose. Few studies have evaluated the A1C–fasting plasma glucose (FPG) relationship and whether oral antidiabetes drugs (OADs) and ethnic or geographic variations affect the relationship. Baseline A1C and FPG data from the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial participants were analyzed to 1) elucidate the relationship between A1C and FPG in people with moderate dysglycemia (A1C 5.6–9.0% [38–75 mmol/mol]) and additional risk factors for cardiovascular disease, 2) determine whether this relationship is altered by use of an OAD, and 3) study whether geographic and ethnic differences exist. RESEARCH DESIGN AND METHODS Analysis was performed of 12,527 participants with dysglycemia or early type 2 diabetes recruited in North America, South America, Europe, Australia, and Asia who comprised white, Latin American, Asian, black, and other ethnicities. The A1C-FPG relationships were analyzed using cubic B spline curves in all participants and in subgroups not using an OAD or using an OAD and comprising persons of different ethnic or geographic origin. RESULTS A strong relationship between FPG in the range of 5.6–9.0 mmol/L and the corresponding A1C was seen across different geographic regions and ethnic groups. A smaller increase in A1C per unit increase in FPG occurred for persons taking an OAD versus those not taking an OAD. CONCLUSIONS The strong relationship between A1C and FPG in moderate dysglycemia is not significantly affected by ethnic or geographic differences. Use of an OAD alters the relationship and should be considered when interpreting A1C level. PMID:22323416

  9. Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels.

    PubMed

    Drevets, Wayne C; Price, Joseph L; Bardgett, Mark E; Reich, Theodore; Todd, Richard D; Raichle, Marcus E

    2002-03-01

    In a previous positron emission tomography (PET) study of major depression, we demonstrated that cerebral blood flow was increased in the left amygdala in unipolar depressives with familial pure depressive disease (FPDD) relative to healthy controls [J. Neurosci. 12 (1992) 3628.]. These measures were obtained from relatively low-resolution PET images using a stereotaxic method based upon skull X-ray landmarks. The current experiments aimed to replicate and extend these results using higher-resolution glucose metabolism images and magnetic resonance imaging (MRI)-based region-of-interest (ROI) analysis. The specificity of this finding to FPDD was also investigated by assessing depressed samples with bipolar disorder (BD-D) and depression spectrum disease (DSD). Finally, the relationship between amygdala metabolism and plasma cortisol levels obtained during the scanning procedure was assessed. Glucose metabolism was measured using PET and 18F-fluorodeoxyglucose (18FDG) in healthy control (n=12), FPDD (n=12), DSD (n=9) and BD-D (n=7) samples in the amygdala and the adjacent hippocampus. The left amygdala metabolism differed across groups (P<.001), being increased in both the FPDD and BD-D groups relative to the control group. The left amygdala metabolism was positively correlated with stressed plasma cortisol levels in both the unipolar (r=.69; P<.005) and the bipolar depressives (r=0.68;.1plasma cortisol were evident in post hoc analyses of metabolism in the right amygdala or the hippocampus. Preliminary assessment of BD subjects imaged during remission suggested that amygdala metabolism is also elevated in remitted subjects who are not taking mood-stabilizing drugs, but within the normal range in subjects taking mood stabilizers. These data confirm our previous finding that neurophysiological activity is abnormally increased in FPDD, and extend it to BD-D. These

  10. Glucose Starvation Inhibits Autophagy via Vacuolar Hydrolysis and Induces Plasma Membrane Internalization by Down-regulating Recycling*

    PubMed Central

    Lang, Michael J.; Martinez-Marquez, Jorge Y.; Prosser, Derek C.; Ganser, Laura R.; Buelto, Destiney; Wendland, Beverly; Duncan, Mara C.

    2014-01-01

    Cellular energy influences all aspects of cellular function. Although cells can adapt to a gradual reduction in energy, acute energy depletion poses a unique challenge. Because acute depletion hampers the transport of new energy sources into the cell, the cell must use endogenous substrates to replenish energy after acute depletion. In the yeast Saccharomyces cerevisiae, glucose starvation causes an acute depletion of intracellular energy that recovers during continued glucose starvation. However, how the cell replenishes energy during the early phase of glucose starvation is unknown. In this study, we investigated the role of pathways that deliver proteins and lipids to the vacuole during glucose starvation. We report that in response to glucose starvation, plasma membrane proteins are directed to the vacuole through reduced recycling at the endosomes. Furthermore, we found that vacuolar hydrolysis inhibits macroautophagy in a target of rapamycin complex 1-dependent manner. Accordingly, we found that endocytosis and hydrolysis are required for survival in glucose starvation, whereas macroautophagy is dispensable. Together, these results suggest that hydrolysis of components delivered to the vacuole independent of autophagy is the cell survival mechanism used by S. cerevisiae in response to glucose starvation. PMID:24753258

  11. The natural 13C abundance of plasma glucose is a useful biomarker of recent dietary caloric sweetener intake.

    PubMed

    Cook, Chad M; Alvig, Amy L; Liu, Yu Qiu David; Schoeller, Dale A

    2010-02-01

    There is a need for objective biomarkers of dietary intake, because self-reporting is often subject to bias. We tested the validity of a biomarker for the fraction of dietary carbohydrate (CHO) from cane sugar and high fructose corn syrup (C(4) sugars) using natural (13)C abundance of plasma glucose. In a randomized, single-blinded, crossover design, 5 participants consumed 3 weight-maintaining diets for 7 d, with a 2-wk washout between diet periods. Diets differed in the fraction of total CHO energy from C(4) sugars (5, 16, or 32%). During each diet period, blood samples were drawn at hours 0800 and 1600 on d 1, 3, and 5 and at 0800, 1000, 1200, 1400, and 1600 on d 7. The delta(13)C abundance of plasma glucose was analyzed via GC- isotope ratio MS. Within each diet period, delta(13)C abundance of the 0800 fasting glucose did not change from baseline with increasing time during a diet period; however, there was a strong positive correlation (R(2) = 0.89) between delta(13)C abundance of the glucose concentration at 1000 on d 7 and the percent of breakfast CHO from C(4) sugars. Also, delta(13)C abundance of the combined plasma glucose samples on d 7 demonstrated a strong positive correlation (R(2) = 0.90) with the percent of total daily CHO from C(4) sugars. The natural delta(13)C abundance of postprandial plasma glucose relative to dietary C(4) CHO content was a valid biomarker for contributions of C(4) caloric sweeteners from the previous meal. PMID:20018804

  12. The effect of low zinc (Zn) intake on the plasma Zn response to a meal or glucose load

    SciTech Connect

    Hambidge, K.M.; Mellman, D.; Westcott, J.L. )

    1991-03-15

    The objective of this study was to test the hypothesis that the post-prandial net efflux of Zn from the plasma compartment is greater following a period of acute Zn deprivation. For 8 days, 5 healthy adults received their normal diet plus a 15 mg Zn supplement, following which they were fed a liquid synthetic egg albumin, high phytate diet providing less than 1 mg Zn per day for 8 days. On the 7th day on each diet, subjects were fed the low Zn liquid breakfast providing 240-400 kcal according to body weight. On the 8th day on each diet, subjects received an isocaloric quantity of glucose. Blood samples were collected before and for 6 hrs after both the test breakfast and glucose load. Post-prandial changes in plasma Zn were analyzed by a two-factor analysis of variance with repeated measures. Mean fasting plasma Zn did not change after a week of severe dietary Zn restriction. Post glucose decline in plasma Zn did not change significantly, but post-breakfast decline in plasma Zn was consistently greater across the 6 hr period. The maximal post-prandial decline was 11.6 {plus minus} 6.1 ug/dl in the control period and 19.3 {plus minus} 2.6 ug/dl in the Zn restricted period. It is concluded that the plasma Zn response is greater with a meal than with an equicaloric glucose load and that plasma Zn is more sensitive to a Zn restricted diet post-prandially than in the fasting state.

  13. Differences in neutral amino acid and glucose transport between brush border and basolateral plasma membrane of intestinal epithelial cells.

    PubMed

    Hopfer, U; Sigrist-Nelson, K; Ammann, E; Murer, H

    1976-12-01

    A comparison of L-valine and D-glucose transport was carried out with vesicles of plasma membrane isolated either from the luminal (brush border) or from the contra-luminal (basolateral) region of small intestinal epithelial cells. The existence of transport systems for both non-electrolytes was demonstrated by stereospecificity and saturability of uptake, as well as tracer coupling. Transport of L-valine and D-glucose differs markedly in the two types of plasma membrane with respect to stimulation by Na+. The presence of Na+ stimulated initial L-valine and D-glucose uptake in brush border, but not in basolateral membrane. Moreover, an electro-chemical Na+ gradient, oriented with the lower potential on the inside, supported accumulation of the non-electrolytes above medium concentration only in the brush border membrane. L-Valine and D-glucose transport also were saturated at lower concentrations in brush border (10-20 mM) than in basolateral plasma membranes (30-50 mM). A third difference between the two membranes was found in the effectiveness of known inhibitors of D-glucose transport. In brush border membranes phlorizin was more potent than phloretin and 2', 3', 4'-trihydroxy-4-methoxy chalcone and cytochalasin B did not inhibit at all. In contrast, with the basolateral plasma membranes the order of potency was changed to phloretin = 2',3',4'-trihydroxy-4-methoxy chalcone greater than cytochalasin B greater than phlorizin. These results indicate the presence of different types of transport systems for monosaccharides and neutral amino acids in the luminal and contra-luminal region of the plasma membrane. Active transepithelial transport can be explained on the basis of the different properties of the non-electrolyte transport systems in the two cellular regions and an electro-chemical Na+ gradient that is dependent on cellular metabolism. PMID:137908

  14. Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects.

    PubMed Central

    Bogardus, C; Lillioja, S; Howard, B V; Reaven, G; Mott, D

    1984-01-01

    The relationships between insulin secretion, insulin action, and fasting plasma glucose concentration (FPG) were examined in 34 southwest American Indians (19 nondiabetics, 15 noninsulin-dependent diabetics) who had a broad range of FPG (88-310 mg/100 ml). Fasting, glucose-stimulated, and meal-stimulated plasma insulin concentrations were negatively correlated with FPG in diabetics but not in nondiabetics. In contrast, fasting and glucose-stimulated plasma C-peptide concentrations did not decrease with increasing FPG in either group and 24-h urinary C-peptide excretion during a diet of mixed composition was positively correlated with FPG for all subjects (r = 0.36, P less than 0.05). Fasting free fatty acid (FFA) was correlated with FPG in nondiabetics (r = 0.49, P less than 0.05) and diabetics (r = 0.77, P less than 0.001). Fasting FFA was also correlated with the isotopically determined endogenous glucose production rate in the diabetics (r = 0.54, P less than 0.05). Endogenous glucose production was strongly correlated with FPG in the diabetics (r = 0.90, P less than 0.0001), but not in the nondiabetics. Indirect calorimetry showed that FPG was also negatively correlated with basal glucose oxidation rates (r = -0.61, P less than 0.001), but positively with lipid oxidation (r = 0.74, P less than 0.001) in the diabetics. Insulin action was measured as total insulin-mediated glucose disposal, glucose oxidation, and storage rates, using the euglycemic clamp with simultaneous indirect calorimetry at plasma insulin concentrations of 135 +/- 5 and 1738 +/- 59 microU/ml. These parameters of insulin action were significantly, negatively correlated with FPG in the nondiabetics at both insulin concentrations, but not in the diabetics although all the diabetics had markedly decreased insulin action. We conclude that decreased insulin action is present in the noninsulin-dependent diabetics in this population and marked hyperglycemia occurs with the addition of decreased

  15. Amperometric, screen-printed, glucose biosensor for analysis of human plasma samples using a biocomposite water-based carbon ink incorporating glucose oxidase.

    PubMed

    Crouch, Eric; Cowell, David C; Hoskins, Stephen; Pittson, Robin W; Hart, John P

    2005-12-01

    This paper describes the optimisation of a screen-printing water-based carbon ink containing cobalt phthalocyanine (CoPC) and glucose oxidase (GOD) for the fabrication of a glucose biosensor. To optimise the performance of the biosensor, the loadings of the electrocatalyst (CoPC) and enzyme (GOD) were varied. It was found that the maximum linear range was achieved with a CoPC loading of 20% (m/m, relative to the mass of carbon) and a GOD loading of 628 U per gram of carbon. In our studies we chose to employ chronoamperometry, as this technique is commonly used for commercial devices. The optimum operating applied potential was found to be +0.5 V, following an incubation period of 60 s. The optimum supporting electrolyte was found to be 0.05 M phosphate buffer at pH 8.0, which resulted in a linear range of 0.2-5 mM, the former represents the detection limit. The sensitivity was 1.12 microA mM(-1). The effect of temperature was also investigated, and it was found that 40 degrees C gave optimal performance. The resulting amperometric biosensors were evaluated by measuring the glucose concentrations for 10 different human plasma samples containing endogenous glucose and also added glucose. The same samples were analysed by a standard spectrophotometric method, and the results obtained by the two different methods were compared. A good correlation coefficient (R(2) = 0.95) and slope (0.98) were calculated from the experimental data, indicating that the new devices hold promise for biomedical studies. PMID:16266677

  16. Rapidly alternating photoperiods disrupt central and peripheral rhythmicity and decrease plasma glucose, but do not affect glucose tolerance or insulin secretion in sheep.

    PubMed

    Varcoe, Tamara J; Gatford, Kathryn L; Voultsios, Athena; Salkeld, Mark D; Boden, Michael J; Rattanatray, Leewen; Kennaway, David J

    2014-09-01

    Disrupting circadian rhythms in rodents perturbs glucose metabolism and increases adiposity. To determine whether these effects occur in a large diurnal animal, we assessed the impact of circadian rhythm disruption upon metabolic function in sheep. Adult ewes (n = 7) underwent 3 weeks of a control 12 h light-12 h dark photoperiod, followed by 4 weeks of rapidly alternating photoperiods (RAPs) whereby the time of light exposure was reversed twice each week. Measures of central (melatonin secretion and core body temperature) and peripheral rhythmicity (clock and metabolic gene expression in skeletal muscle) were obtained over 24 h in both conditions. Metabolic homeostasis was assessed by glucose tolerance tests and 24 h glucose and insulin profiles. Melatonin and core body temperature rhythms resynchronized within 2 days of the last photoperiod shift. High-amplitude Bmal1, Clock, Nr1d1, Cry2 and Per3 mRNA rhythms were apparent in skeletal muscle, which were phase advanced by up to 3.5 h at 2 days after the last phase shift, whereas Per1 expression was downregulated at this time. Pparα, Pgc1α and Nampt mRNA were constitutively expressed in both conditions. Nocturnal glucose concentrations were reduced following chronic phase shifts (zeitgeber time 0, -5.5%; zeitgeber time 12, -2.9%; and zeitgeber time 16, -5.7%), whereas plasma insulin, glucose tolerance and glucose-stimulated insulin secretion were not altered. These results demonstrate that clock gene expression within ovine skeletal muscle oscillates over 24 h and responds to changing photoperiods. However, metabolic genes which link circadian and metabolic clocks in rodents were arrhythmic in sheep. Differences may be due to the ruminant versus monogastric digestive organization in each species. Together, these results demonstrate that despite disruptions to central and peripheral rhythmicity following exposure to rapidly alternating photoperiods, there was minimal impact on glucose homeostasis in

  17. U1h Superstructure

    SciTech Connect

    Glen Sykes

    2000-11-01

    The U1H Shaft Project is a design build subcontract to supply the U. S. Department of Energy (DOE) a 1,045 ft. deep, 20 ft. diameter, concrete lined shaft for unspecified purposes. The subcontract awarded to Atkinson Construction by Bechtel Nevada to design and construct the shaft for the DOE has been split into phases with portions of the work being released as dictated by available funding. The first portion released included the design for the shaft, permanent hoist, headframe, and collar arrangement. The second release consisted of constructing the shaft collar to a depth of 110 ft., the service entry, utility trenches, and installation of the temporary sinking plant. The temporary sinking plant included the installation of the sinking headframe, the sinking hoist, two deck winches, the shaft form, the sinking work deck, and temporary utilities required to sink the shaft. Both the design and collar construction were completed on schedule. The third release consisted of excavating and lining the shaft to the station depth of approximately 950 feet. Work is currently proceeding on this production sinking phase. At a depth of approximately 600 feet, Atkinson has surpassed production expectation and is more than 3 months ahead of schedule. Atkinson has employed the use of a Bobcat 331 excavator as the primary means of excavation. the shaft is being excavated entirely in an alluvial deposit with varying degrees of calcium carbonate cementation. Several more work packages are expected to be released in the near future. The remaining work packages include, construction of the shaft station a depth of 975 ft. and construction of the shaft sump to a depth of 1,045 ft., installation of the loading pocket and station steel and equipment, installation of the shaft steel and guides, installation of the shaft utilities, and installation of the permanent headframe, hoist, collar utilities, and facilities.

  18. Quantitative study of starving platelets in a minimal medium: maintenance by acetate or plasma but not by glucose.

    PubMed

    Whisson, M E; Nakhoul, A; Howman, P; Niu, X; Guppy, M

    1993-06-01

    The requirement of donor platelets for fuels, plasma and calcium were studied using platelets washed, filtered to remove leucocytes and resuspended in a new glucose-free minimal platelet storage medium with low citrate (3 mmol/l), low buffer capacity and no calcium. This is the first study of platelets stored without plasma, glucose or calcium and it was shown that platelets continued to aggregate with collagen plus adrenaline for 48 h and showed only a 50% fall in 'swirl index', an objective morphology score, after 3 days, showing that by these criteria human platelets do not require glucose. Sodium acetate extended the storage time by between 2 and 4 days, depending on the index parameter. This is the first evidence showing that failure of platelets in these conditions is at least partly due to exhaustion of fuel, and the first evidence that acetate prolongs in vitro survival. As little as 10% low-glucose plasma extended the storage time, but it was no better than acetate. New observations using this system included a very rapid fall in pH during resuspension of the washed platelet pellet, a rising pH in the absence of added fuel and an increased pH with added acetate. PMID:8374698

  19. Effects of piragliatin, a glucokinase activator, on fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus.

    PubMed

    Zhi, Jianguo; Zhai, Suoping

    2016-02-01

    To assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of piragliatin, a double-blind, randomized, placebo-controlled, multiple-ascending-doses study was conducted in patients with type 2 diabetes mellitus (T2D). Fifty-nine T2D patients were given piragliatin or placebo in a dose-escalation design as a single dose on day 1 followed by multiple doses on days 3 through 8 at doses of 10, 25, 50, 100, and 200 mg twice a day (BID) as well as 200 mg every day (QD). Blood and urine samples were collected for PK analysis. PD assessments included plasma glucose, insulin, C-peptide, glucagon, and GLP-1. Piragliatin exposure was dose proportional without appreciable accumulation or food effect. Piragliatin treatment at steady state yielded dose-dependent reductions up to 32.5% and 35.5% for the highest dose in fasting and postprandial plasma glucose. Piragliatin was well tolerated. Mild or moderate hypoglycemia with rapid recovery after sugar-containing drinks or scheduled meals was the only dose-limiting adverse event. It is concluded that multiple doses of piragliatin consistently showed rapid, dose-dependent glucose reduction of fasting and postprandial plasma glucose in T2D patients. PMID:26183686

  20. Effects of low-dose thiazide diuretics on fasting plasma glucose and serum potassium-a meta-analysis.

    PubMed

    Mukete, Bertrand N; Rosendorff, Clive

    2013-01-01

    This study is a meta-analysis of the metabolic profile (fasting plasma glucose and serum potassium) of low-dose thiazide and thiazide-like diuretics. The meta-analysis involved 10 randomized controlled clinical trials with a total sample size of 17,636 and 17,947 for the potassium and glucose arms respectively. The random effect model was used to calculate the odds ratio with 95 percent confidence interval. The cumulative mean change of fasting plasma glucose was +0.20 mmol/L (+3.6 mg/dL) for the diuretic arm versus +0.12 mmol/L (+2.2 mg/dL) for the comparator arm. The cumulative mean change of serum potassium was -0.22 mmol/L (-0.22 mEq/L) for the diuretic arm versus +0.05 mmol/L (+0.05 mEq/L) for the comparator arm. The aggregate odds ratio for having higher fasting plasma glucose in subjects on low-dose thiazide versus non-thiazide antihypertensive was 1.22 (1.11 to 1.33; P < .01). The odds ratio for having a lower serum potassium in subjects on low-dose thiazide versus non-thiazide antihypertensive was 0.36 (0.27 to 0.49; P < .01). The magnitude of the observed change in fasting plasma glucose associated with low-dose thiazide diuretic use, while statistically significant, does not appear to place patients at clinically significant risk. On the other hand, the observed change in serum potassium was also statistically significant, and may be clinically significant in patients whose baseline potassium concentration is low or low-normal, and could predispose at-risk patients, such as those with ischemic heart disease, to ventricular arrhythmias. PMID:23800570

  1. The Prevalence and Associated Factors of Periodontitis According to Fasting Plasma Glucose in the Korean Adults

    PubMed Central

    Hong, Jae Won; Noh, Jung Hyun; Kim, Dong-Jun

    2016-01-01

    Abstract Although the relationship between diabetes and periodontitis is well established, the association between periodontitis and prediabetes has been investigated less extensively. Furthermore, there has been little research on the prevalence of periodontitis among individuals with prediabetes and diabetes as well as in the overall population using nationally representative data. Among 12,406 adults (≥19 years’ old) who participated in the 2012–2013 Korea National Health and Nutrition Examination Survey, a total of 9977 subjects completed oral and laboratory examinations and were included in this analysis. Periodontitis was defined as a community periodontal index score of ≥3 according to the World Health Organization criteria. The fasting plasma glucose level was categorized into the following 5 groups: normal fasting glucose (NFG) 1 (<90 mg/dL), NFG 2 (90–99 mg/dL), impaired fasting glucose (IFG) 1 (100–110 mg/dL), IFG 2 (111–125 mg/dL), and diabetes (≥126 mg/dL). Overall, the weighted prevalence of periodontitis among the Korean adult population was 24.8% (23.3–26.4%) (weight n = 8,455,952/34,086,014). The unadjusted weighted prevalences of periodontitis were 16.7%, 22.8%, 29.6%, 40.7%, and 46.7% in the NFG 1, NFG 2, IFG 1, IFG 2, and diabetes groups, respectively (P < 0.001). After adjusting for age, sex, smoking history, heavy alcohol drinking, college graduation, household income, waist circumference, serum triglyceride level, serum high-density lipoprotein cholesterol level, and the presence of hypertension, the adjusted weighted prevalence of periodontitis increased to 29.7% in the IFG 2 group (P = 0.045) and 32.5% in the diabetes group (P < 0.001), compared with the NFG 1 group (24%). The odds ratios for periodontitis with the above-mentioned variables as covariates were 1.42 (95% confidence interval [CI] 1.14–1.77, P = 0.002) in the diabetes group and 1.33 (95% CI 1.01–1.75, P = 0.044) in the IFG

  2. Effect of acute hyperglycemia on potassium (86Rb+) permeability and plasma lipid peroxidation in subjects with normal glucose tolerance.

    PubMed

    Güven, M; Onaran, I; Ulutin, T; Sultuybek, G; Hatemi, H

    2001-04-01

    Hyperglycemia is likely to be one of the important determinants of ion transport as it is known to induce oxidative stress and may thus enhance non-specific permeability of membranes. The aim of the present study was to evaluate the effects of an acute increase in glycemia on 86Rb+ (a marker for K+) influx and lipid peroxidation. We evaluated the 75-g oral glucose tolerance test (OGTT)-induced modification on 86Rb+ influx and plasma lipid peroxidation in 20 subjects with normal glucose tolerance (NGT). After 2-hour glucose loading, the levels of passive 86Rb+ influx and plasma lipid peroxidation were significantly increased, whereas the active influx of 86Rb+ was unchanged. The total and passive influx of 86Rb+ into erythrocytes was significantly correlated with the level of plasma lipid peroxidation. This study demonstrates that acute hyperglycemia induces an increase in the passive influx of 86Rb+ in subjects with NGT, suggesting that acute hyperglycemia may produce an oxidative stress in plasma. These changes may be among the earliest changes occurring in response to hyperglycemia. PMID:11383909

  3. Effect of acute hyperglycemia on potassium (86Rb+) permeability and plasma lipid peroxidation in subjects with normal glucose tolerance.

    PubMed

    Güven, M; Onaran, I; Ulutin, T; Sultuybek, G; Hatemi, H

    2001-01-01

    Hyperglycemia is likely to be one of the important determinants of ion transport as it is known to induce oxidative stress and may thus enhance non-specific permeability of membranes. The aim of the present study was to evaluate the effects of an acute increase in glycemia on 86Rb+ (a marker for K+) influx and lipid peroxidation. We evaluated the 75-g oral glucose tolerance test (OGTT)-induced modification on 86Rb+ influx and plasma lipid peroxidation in 20 subjects with normal glucose tolerance (NGT). After 2-hour glucose loading, the levels of passive 86Rb+ influx and plasma lipid peroxidation were significantly increased, whereas the active influx of 86Rb+ was unchanged. The total and passive influx of 86Rb+ into erythrocytes was significantly correlated with the level of plasma lipid peroxidation. This study demonstrates that acute hyperglycemia induces an increase in the passive influx of 86Rb+ in subjects with NGT, suggesting that acute hyperglycemia may produce an oxidative stress in plasma. These changes may be among the earliest changes occurring in response to hyperglycemia. PMID:11508792

  4. 1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women.

    PubMed

    Ghio, Alessandra; Seghieri, Giuseppe; Lencioni, Cristina; Anichini, Roberto; Bertolotto, Alessandra; De Bellis, Alessandra; Resi, Veronica; Lacaria, Emilia; Del Prato, Stefano; Di Cianni, Graziano

    2012-01-01

    Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL, n = 661; 120-139 mg/dL, n = 710; 140-159 mg/dL, n = 912; 160-179 mg/dL, n = 885; and ≥180 mg/dL, n = 996). We calculated incremental area under glucose (AUC(gluc)) and insulin curves (AUC(ins)), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUC(ins)/AUC(gluc). AUC(gluc) and AUC(ins) progressively increased according to 1-hour plasma glucose concentrations (both P < 0.0001 for trend). HOMA-B progressively declined (P < 0.001), and HOMA-R progressively increased across the five groups. AUC(ins)/AUC(gluc) decreased in a linear manner across the 5 groups (P < 0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: -29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (all P < 0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion. PMID:22567007

  5. 1H- and 2H-NMR studies of a fragment of PMP1, a regulatory subunit associated with the yeast plasma membrane H(+)-ATPase. Conformational properties and lipid-peptide interactions.

    PubMed

    Beswick, V; Roux, M; Navarre, C; Coïc, Y M; Huynh-Dinh, T; Goffeau, A; Sanson, A; Neumann, J M

    1998-01-01

    PMP1 is a 38-residue polypeptide associated with the yeast plasma membrane H(+)-ATPase, found to regulate the enzyme activity. To investigate the molecular basis of the PMP1 biological function, the conformational properties of a synthetic PMP1 fragment, A18-F38, comprising the predicted C-terminal cytoplasmic domain and a part of the transmembrane anchor have been studied by 1H- and 2H-NMR spectroscopies. High resolution 1H-NMR experiments showed that, in deuterated DPC micelles, the A18-G34 segment adopts a well defined helix conformation. Our data suggest that the whole PMP1 molecule forms a unique helix whose axis might be slightly tilted with respect to the bilayer normal. Protonated DPC, DMPC and DMPS were incorporated in deuterated micelles containing the PMP1 fragment for studying lipid-peptide interactions. Unusually strong and selective intermolecular NOEs between lipid chain and peptide side chain protons, especially those of the unique Trp residue, were observed. Solid state 2H-NMR experiments performed on pure deuterated POPC and mixed deuterated POPC:POPS (5:1) bilayers revealed that the PMP1 fragment specifically interacts with negatively charged PS lipids. PMID:9782385

  6. Plasma lactate and glucose flushes following burst swimming in silver trevally (Pseudocaranx dentex: Carangidae) support the "releaser" hypothesis.

    PubMed

    Wells, R M G; Baldwin, J

    2006-03-01

    Silver trevally (Pseudocaranx dentex) are highly athletic marine teleosts inhabiting the tropical waters of the Great Barrier Reef, Australia. Burst swimming increased plasma lactate from 1.6 +/- 0.4 S.D. to 21.6 +/- 3.3 mM (N = 6), among the highest values reported for functional hypoxia in fish. These data support the hypothesis that elite swimmers release lactate produced in the myotome into the circulation following anaerobic burst activity. The fish further developed a hyperglycaemic response to burst exercise with plasma glucose increasing from 6.6 +/- 2.0 to 13.2 +/- 2.3 mM (N = 6). Post-exercise erythrocyte swelling also occurred, but nucleoside triphosphate levels remained unaltered and do not provide a mechanism to modulate haemoglobin function during exercise. Metabolism of the blood cells appeared to be fuelled by both lactate and glucose. PMID:16459118

  7. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    NASA Astrophysics Data System (ADS)

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  8. Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1.

    PubMed

    Huang, Ping; Altshuller, Yelena M; Hou, June Chunqiu; Pessin, Jeffrey E; Frohman, Michael A

    2005-06-01

    Insulin stimulates glucose uptake in fat and muscle by mobilizing Glut4 glucose transporters from intracellular membrane storage sites to the plasma membrane. This process requires the trafficking of Glut4-containing vesicles toward the cell periphery, docking at exocytic sites, and plasma membrane fusion. We show here that phospholipase D (PLD) production of the lipid phosphatidic acid (PA) is a key event in the fusion process. PLD1 is found on Glut4-containing vesicles, is activated by insulin signaling, and traffics with Glut4 to exocytic sites. Increasing PLD1 activity facilitates glucose uptake, whereas decreasing PLD1 activity is inhibitory. Diminished PA production does not substantially hinder trafficking of the vesicles or their docking at the plasma membrane, but it does impede fusion-mediated extracellular exposure of the transporter. The fusion block caused by RNA interference-mediated PLD1 deficiency is rescued by exogenous provision of a lipid that promotes fusion pore formation and expansion, suggesting that the step regulated by PA is late in the process of vesicle fusion. PMID:15772157

  9. The effects of combined vitamin D and calcium supplementation on fasting plasma glucose in non-diabetic adults age 65 and older

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Altered vitamin D and calcium homeostasis may play a role in the development of glucose intolerance. In a 3-year randomized controlled trial, we compared the effects of combined vitamin D and calcium supplementation vs. placebo on fasting plasma glucose (FPG) in healthy adults 65 years of age or old...

  10. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: 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...

  11. The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study.

    PubMed

    Krysiak, Robert; Okrzesik, Joanna; Okopien, Boguslaw

    2015-05-01

    Metformin was found to affect plasma levels of some pituitary hormones. This study was aimed at investigating whether metformin treatment has an impact on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance. The study included 27 patients with hyperprolactinaemia, who had been treated for at least 6 months with bromocriptine. Based on prolactin levels, bromocriptine-treated patients were divided into two groups: patients with elevated (group A, n = 12) and patients with normal (group B, n = 15) prolactin levels. The control group included 16 age-, sex- and weight-matched hyperprolactinaemia-free individuals with impaired glucose tolerance (group C).The lipid profile, fasting plasma glucose levels, the homeostatic model assessment of insulin resistance ratio (HOMA-IR), glycated haemoglobin, as well as plasma levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment (2.55-3 g daily). In all treatment groups, metformin reduced HOMA-IR, plasma triglycerides and 2-h postchallenge plasma glucose. In patients with hyperprolactinaemia, but not in the other groups of patients, metformin slightly reduced plasma levels of prolactin, and this effect correlated weakly with the metabolic effects of this drug. Our study shows that metformin decreases plasma prolactin levels only in patients with elevated levels of this hormone. The obtained results suggest that metformin treatment may bring some benefits to hyperprolactinaemic patients with coexisting glucose metabolism disturbances already receiving dopamine agonist therapy. PMID:25239203

  12. 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

  13. Effects of Rice Straw Supplemented with Urea and Molasses on Intermediary Metabolism of Plasma Glucose and Leucine in Sheep.

    PubMed

    Alam, Mohammad Khairul; Ogata, Yasumichi; Sato, Yukari; Sano, Hiroaki

    2016-04-01

    An isotope dilution method using [U-(13)C]glucose and [1-(13)C]leucine (Leu) was conducted to evaluate the effects of rice straw supplemented with urea and molasses (RSUM-diet) on plasma glucose and Leu turnover rates in sheep. Nitrogen (N) balance, rumen fermentation characteristics and blood metabolite concentrations were also determined. Four sheep were fed either mixed hay (MH-diet), or a RSUM-diet with a crossover design for two 21 days period. Feed allowance was computed on the basis of metabolizable energy at maintenance level. The isotope dilution method was performed as the primed-continuous infusion on day 21 of each dietary period. Nitrogen intake was lower (p = 0.01) for the RSUM-diet and N digestibility did not differ (p = 0.57) between diets. Concentrations of rumen total volatile fatty acids tended to be higher (p = 0.09) for the RSUM-diet than the MH-diet. Acetate concentration in the rumen did not differ (p = 0.38) between diets, whereas propionate concentration was higher (p = 0.01) for the RSUM-diet compared to the MH-diet. Turnover rates as well as concentrations of plasma glucose and Leu did not differ between diets. It can be concluded that kinetics of plasma glucose and Leu metabolism were comparable between the RSUM-diet and the MH-diet, and rumen fermentation characteristics were improved in sheep fed the RSUM-diet compared to the MH-diet. PMID:26949953

  14. Effects of Rice Straw Supplemented with Urea and Molasses on Intermediary Metabolism of Plasma Glucose and Leucine in Sheep

    PubMed Central

    Alam, Mohammad Khairul; Ogata, Yasumichi; Sato, Yukari; Sano, Hiroaki

    2016-01-01

    An isotope dilution method using [U-13C]glucose and [1-13C]leucine (Leu) was conducted to evaluate the effects of rice straw supplemented with urea and molasses (RSUM-diet) on plasma glucose and Leu turnover rates in sheep. Nitrogen (N) balance, rumen fermentation characteristics and blood metabolite concentrations were also determined. Four sheep were fed either mixed hay (MH-diet), or a RSUM-diet with a crossover design for two 21 days period. Feed allowance was computed on the basis of metabolizable energy at maintenance level. The isotope dilution method was performed as the primed-continuous infusion on day 21 of each dietary period. Nitrogen intake was lower (p = 0.01) for the RSUM-diet and N digestibility did not differ (p = 0.57) between diets. Concentrations of rumen total volatile fatty acids tended to be higher (p = 0.09) for the RSUM-diet than the MH-diet. Acetate concentration in the rumen did not differ (p = 0.38) between diets, whereas propionate concentration was higher (p = 0.01) for the RSUM-diet compared to the MH-diet. Turnover rates as well as concentrations of plasma glucose and Leu did not differ between diets. It can be concluded that kinetics of plasma glucose and Leu metabolism were comparable between the RSUM-diet and the MH-diet, and rumen fermentation characteristics were improved in sheep fed the RSUM-diet compared to the MH-diet. PMID:26949953

  15. Comparison of several insulin sensitivity indices derived from basal plasma insulin and glucose levels with minimal model indices.

    PubMed

    García-Estévez, D A; Araújo-Vilar, D; Fiestras-Janeiro, G; Saavedra-González, A; Cabezas-Cerrato, J

    2003-01-01

    Some techniques for the evaluation of insulin resistance (IR), such as the clamp technique, are not viable for the study of large populations; and for this reason, alternative approaches based on fasting plasma glucose (FPG) and plasma insulin (FPI) have been proposed. The aim of this study was to compare the IR calculations obtained from FPI and FPG values with the insulin sensitivity (IS) index derived from the minimal model. Eighty-seven healthy subjects with a wide range of body mass index (18 - 44 kg x m -2) and 16 DM2 non-obese patients were included in the study. All of the patients underwent a frequently sampled intravenous glucose tolerance test (FSIGTT), and the minimal model of glucose was used for the estimation of insulin sensitivity (IS MINIMAL ). The HOMA-IR index, the Avignon index, and the quotient FPG/FPI were used to calculate basal steady-state IR. The basal IR value that best correlated with IS was Log (1/HOMA-IR) (r = 0.70, p < 0.001). All of the basal indices showed a high correlation with each other. In conclusions, insulin sensitivity indices as determined from the basal glycaemia and insulinemia values are not good estimators for metabolic reality from the perspective of the minimal model. Nevertheless, they might well have an IR screening value for epidemiological studies, as long as there is no pancreatic beta-cell dysfunction. PMID:12669265

  16. Influence of Acarbose on Plasma Glucose Fluctuations in Insulin-Treated Patients with Type 2 Diabetes: A Pilot Study

    PubMed Central

    Li, Feng-fei; Xu, Xiao-hua; Fu, Li-yuan; Su, Xiao-fei; Wu, Jin-dan; Lu, Chun-feng; Ye, Lei; Ma, Jian-hua

    2015-01-01

    Background and Aims. To evaluate the effect of adding acarbose on glycemic excursions measured by continuous glucose monitoring system (CGMS) in patients with type 2 diabetes mellitus (T2DM) already on insulin therapy. Materials and Methods. This was an opened and unblended study. 134 patients with T2DM were recruited. After initial rapidly corrected hyperglycaemia by continuous subcutaneous insulin infusion (CSII) for 7 d, a 4–6-day premixed insulin titration period subsequently followed. Patients were then randomized 1 : 1 to acarbose plus insulin group or insulin therapy group for 2 weeks. CGMS was used to measure glucose fluctuations for at least 3 days after therapy cessation. Results. Patients in acarbose plus insulin group achieved a significant improvement of MAGE compared to that of insulin therapy only group (5.56 ± 2.16 versus 7.50 ± 3.28 mmol/L, P = 0.044), accompanied by a significant decrease in the incremental AUC of plasma glucose concentration above 10.0 mmol/L (0.5 [0.03, 0.9] versus 0.85 [0.23,1.4]  mmol/L per day, P = 0.037). Conclusions. Add-on acarbose to insulin therapy further improves glucose fluctuation in patients with T2DM. This study was registered with ClinicalTrials.gov registration number ChiCTR-TRC-11001218. PMID:26640487

  17. Chronic growth hormone treatment in normal rats reduces post-prandial skeletal muscle plasma membrane GLUT1 content, but not glucose transport or GLUT4 expression and localization.

    PubMed Central

    Napoli, R; Cittadini, A; Chow, J C; Hirshman, M F; Smith, R J; Douglas, P S; Horton, E S

    1996-01-01

    Whether skeletal muscle glucose transport system is impaired in the basal, post-prandial state during chronic growth hormone treatment is unknown. The current study was designed to determine whether 4 weeks of human growth hormone (hGH) treatment (3.5 mg/kg per day) would impair glucose transport and/or the number of glucose transporters in plasma membrane vesicles isolated from hindlimb skeletal muscle of Sprague-Dawley rats under basal, post-prandial conditions. hGH treatment was shown to have no effect on glucose influx (Vmax or K(m)) determined under equilibrium exchange conditions in isolated plasma membrane vesicles. Plasma membrane glucose transporter number (Ro) measured by cytochalasin B binding was also unchanged by hGH treatment. Consequently, glucose transporter turnover number (Vmax/Ro), a measure of average glucose transporter intrinsic activity, was similar in hGH-treated and control rats. hGH did not change GLUT4 protein content in whole muscle or in the plasma membrane, and muscle content of GLUT4 mRNA also was unchanged. In contrast, GLUT1 protein content in the plasma membrane fraction was significantly reduced by hGH treatment. This was associated with a modest, although not significant, decrease in muscle content of GLUT1 mRNA. In conclusion, high-dose hGH treatment for 4 weeks did not alter post-prandial skeletal muscle glucose transport activity. Neither the muscle level nor the intracellular localization of GLUT4 was changed by the hormone treatment. On the contrary, the basal post-prandial level of GLUT1 in the plasma membrane was reduced by hGH. The mRNA data suggest that this reduction might result from a decrease in the synthesis of GLUT1. PMID:8645183

  18. DEVELOPMENTAL CHANGES OF PLASMA INSULIN, GLUCAGON, INSULIN-LIKE GROWTH FACTORS, THYROID HORMONES AND GLUCOSE CONCENTRATIONS IN CHICK EMBRYOS AND HATCHED CHICKS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The developmental hormonal changes in Cobb 500 chick embryos and hatched chicks were determined by measuring plasma insulin, glucagon, IGF-I, IGF-II, triiodothyronine, thyroxine, and glucose concentrations at different ages of chick embryos and hatched chicks. Plasma samples were obtained daily fro...

  19. Carbon Nanotube-Plasma Polymer-Based Amperometric Biosensors: Enzyme-Friendly Platform for Ultrasensitive Glucose Detection

    NASA Astrophysics Data System (ADS)

    Muguruma, Hitoshi; Matsui, Yasunori; Shibayama, Yu

    2007-09-01

    An amperometric enzyme biosensor fabricated with carbon nanotubes (CNTs) and plasma-polymerized thin films (PPFs) is reported. A mixture of the enzyme glucose oxidase (GOD) and a CNT film is sandwiched with 10-nm-thick acetonitrile PPFs. Under PPF layer was deposited onto a sputtered gold electrode. To facilitate the electrochemical communication between the CNT layer and GOD, CNT was treated with oxygen plasma. The device with single-walled CNTs showed a sensitivity higher than that of multiwalled CNTs. The glucose biosensor showed ultrasensitivity (a sensitivity of 40 μA mM-1 cm-2, a correlation coefficient of 0.992, a linear response range of 0.025-1.9 mM, a detection limit of 6.2 μM at S/N = 3, +0.8 V vs Ag/AgCl), and a rapid response (< 4 s in reaching 95% of maximum response). This high performance is attributed to the fact that CNTs have excellent electrocatalytic activity and enhance electron transfer, and that PPFs and/or the plasma process for CNTs are the enzyme-friendly platform, i.e., a suitable design of the interface between GOD and CNTs.

  20. Fasting modifies Aroclor 1254 impact on plasma cortisol, glucose and lactate responses to a handling disturbance in Arctic charr

    USGS Publications Warehouse

    Jorgensen, E.H.; Vijayan, M.M.; Aluru, N.; Maule, A.G.

    2002-01-01

    Integrated effects of polychlorinated biphenyl (PCB) and nutritional status on responses to handling disturbance were investigated in the Arctic charr (Salvelinus alpinus). The fish were orally contaminated with Aroclor 1254 and held either with or without food for 5 months before they were subjected to a 10-min handling disturbance. Food-deprived fish were given 0, 1, 10 or 100 mg PCB kg-1 and the fed fish 0 or 100 mg PCB kg-1. Plasma cortisol, glucose and lactate levels were measured at 0 (pre-handling), 1, 3, 6 and 23 h after the handling disturbance. Food-deprived control fish had elevated plasma cortisol levels compared with fed fish before handling. These basal cortisol levels were suppressed by PCB in food-deprived fish, and elevated by PCB in fed fish. The immediate cortisol and glucose responses to handling disturbance were suppressed by PCB in a dose-dependent way in food-deprived fish. Although these responses were also lowered by PCB in the fed fish, the effect was much less pronounced than in food-deprived fish. There were only minor effects on plasma lactate responses. Our findings suggest that the stress responses of the Arctic charr are compromised by PCB and that the long-term fasting, typical of high-latitude fish, makes these species particularly sensitive to organochlorines such as PCB. ?? 2002 Elsevier Science Inc. All rights reserved.

  1. Rutin ameliorates diabetic neuropathy by lowering plasma glucose and decreasing oxidative stress via Nrf2 signaling pathway in rats.

    PubMed

    Tian, Ruifeng; Yang, Wenqing; Xue, Qiang; Gao, Liang; Huo, Junli; Ren, Dongqing; Chen, Xiaoyan

    2016-01-15

    Rutin exhibits antidiabetic, antioxidant and anti-inflammatory properties, which makes rutin an attractive candidate for diabetic complications. The present study was designed to investigate the potential effect of rutin on diabetic neuropathy. After induction of diabetic neuropathy, rutin (5mg/kg, 25mg/kg and 50mg/kg) were daily given to the diabetic rats for 2 weeks. At the end of rutin administration, rutin produced a significant inhibition of mechanical hyperalgesia, thermal hyperalgesia and cold allodynia, as well as partial restoration of nerve conduction velocities in diabetic rats. Furthermore, rutin significantly increased Na(+), K(+)-ATPase activities in sciatic nerves and decreased caspase-3 expression in dorsal root ganglions (DRG). In addition, rutin significantly decreased plasma glucose, attenuated oxidative stress and neuroinflammation. Further studies showed that rutin significantly increased hydrogen sulfide (H2S) level, up-regulated the expression of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in DRG. The evidences suggest the beneficial effect of rutin on diabetic neuropathy. Additionally, insulin (2 IU) and BG-12 (15mg/kg) were used to investigate the mechanisms underlying the beneficial effect of rutin on diabetic neuropathy. Insulin achieved lower plasma glucose and BG-12 achieved comparable Nrf2 expression than/to rutin (50mg/kg), respectively. In contrast, the beneficial effect of insulin and BG-12 was inferior to that of rutin (50mg/kg), suggesting that both lowered plasma glucose and Nrf2 signaling contribute to the beneficial effect of rutin on diabetic neuropathy. In conclusion, rutin produces significant protection in diabetic neuropathy, which makes it an attractive candidate for the treatment of diabetic neuropathy. PMID:26688570

  2. The performance of hemoglobin A1c against fasting plasma glucose and oral glucose tolerance test in detecting prediabetes and diabetes

    PubMed Central

    Karakaya, Jale; Akin, Safak; Karagaoglu, Ergun; Gurlek, Alper

    2014-01-01

    Background: In recent years, hemoglobin A1c (HbA1c) is accepted among the algorithms used for making diagnosis for diabetes and prediabetes since it does not require subjects to be prepared for giving a blood sample. The aim of this study is to assess the performance of HbA1c against fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in detecting prediabetes and diabetes. Materials and Methods: A total of 315 subjects were included in this study. The success of HbA1c in distinguishing the three diagnostic classes was examined by three-way receiver operating characteristic (ROC) analysis. The best cut-off points for HbA1c were found for discriminating the three disease status. Results: The performance of HbA1c, measured by the volume under the ROC surface (VUS), is found to be statistically significant (VUS = 0.535, P < 0.001). The best cut-off points for discriminating between normal and prediabetes groups and between prediabetes and diabetes groups are c1 = 5.2% and c2 = 6.4% respectively. Conclusion: The performance of HbA1c in distinguishing between the prediabetes and diabetes groups was higher than its ability in distinguishing between healthy and prediabetes groups. This study provides enough information to understand what proportion of diabetes patients were skipped with the HbA1c especially when the test result is healthy or prediabetes. If a subject was diagnosed as healthy or prediabetes by HbA1c, it would be beneficial to verify the status of that subject by the gold standard test (OGTT and FPG). PMID:25657750

  3. Plasma Periostin Levels Are Increased in Chinese Subjects with Obesity and Type 2 Diabetes and Are Positively Correlated with Glucose and Lipid Parameters

    PubMed Central

    Luo, Yuanyuan; Qu, Hua; Wang, Hang; Wei, Huili; Wu, Jing; Duan, Yang; Liu, Dan; Deng, Huacong

    2016-01-01

    The purpose of this study is to examine the relations among plasma periostin, glucose and lipid metabolism, insulin resistance and inflammation in Chinese patients with obesity (OB), and type 2 diabetes mellitus (T2DM). Plasma periostin levels in the T2DM group were significantly higher than the NGT group (P < 0.01). Patients with both OB and T2DM had the highest periostin levels. Correlation analysis showed that plasma periostin levels were positively correlated with weight, waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), fasting plasma glucose (FPG), 2 h postchallenge plasma glucose (2 h PG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), TNF-α, and IL-6 (P < 0.05 or 0.001) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.001). Multiple linear regression analysis showed that TG, TNF-α, and HOMA-IR were independent related factors in influencing the levels of plasma periostin (P < 0.001). These results suggested that Chinese patients with obesity and T2DM had significantly higher plasma periostin levels. Plasma periostin levels were strongly associated with plasma TG, chronic inflammation, and insulin resistance. PMID:27313402

  4. Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs

    PubMed Central

    Wein, Silvia; Wolffram, Siegfried

    2014-01-01

    Treatment goals of diabetes mellitus type 2 (DMT2) include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (n = 16, body weight = BW 25–30 kg) were fed flavonoid-poor grain-based meals without (GBM) or with quercetin (GBMQ). In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA), and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW) in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW) animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying. PMID:24847478

  5. Change in fasting plasma glucose and incident type 2 diabetes mellitus: results from a prospective cohort study

    PubMed Central

    Mozaffary, Amirhossein; Asgari, Samaneh; Tohidi, Maryam; Kazempour-Ardebili, Sara; Azizi, Fereidoun; Hadaegh, Farzad

    2016-01-01

    Objective To investigate the association between changes in fasting plasma glucose (FPG) values and incident type 2 diabetes (T2D) in a cohort of the Iranian population. Design Prospective cohort study. Setting This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) to investigate the association between change in FPG between baseline examination (1999–2001) and the second visit (2002–2005) with incident T2D. Participants A total of 3981 non-diabetic participants aged ≥20 years. Outcome measure T2D was defined if the participant was using antidiabetic drugs or if FPG was ≥7 mmol/L or if the 2 h post-challenge plasma glucose (2-hPCG) was ≥11.1 mmol/L. Results During a median follow-up of 6.17 years, after the second examination, 288 new cases of T2D were identified. In a multivariate Cox proportional hazard analysis using age as timescale, we presented a simple model including FPG change (HR 1.19, 95% CI 1.07 to 1.33) and baseline waist circumference (WC) (HR 1.004, 95% CI 1.001 to 1.008) with a discriminative power (C-index) of 72%. Furthermore, we showed that the highest quartile of FPG change enhanced the T2D risk to 1.65 (95% CI 1.2 to 2.27) compared with the lowest quartile (p for trend=0.004).The independent risk of FPG change resisted further adjustment with 2-hPCG change. Adding the 2-hPCG change only slightly increased the discriminative power of the model including FPG change and baseline value of WC (0.73% vs 0.72%). After the study population had been limited to those with normal fasting glucose/normal glucose tolerance, FPG change remained an independent predictor (HR 1.57, 95% CI 1.31 to 1.88). Conclusions Two measurements of FPG obtained about 3 years apart can help to identify populations at risk of incident T2D independently of important traditional risk factors and their changes, including 2-hPCG change. PMID:27217283

  6. Effects of glucagon and insulin on plasma glucose, triglyceride, and triglyceride-rich lipoprotein concentrations in laying hens fed diets containing different types of fats.

    PubMed

    Pál, L; Grossmann, R; Dublecz, K; Husvéth, F; Wagner, L; Bartos, A; Kovács, G

    2002-11-01

    The influence of dietary fat supplementations differing in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) on the effects of glucagon and insulin on plasma glucose, triglyceride (TG), and TG-rich lipoprotein concentrations was investigated in laying hens. Birds were fed either a low-fat control diet (LF) or diets supplemented with 4% pumpkin seed oil (PO; rich in n-6 PUFA) or 4% cod liver oil (CO; rich in n-3 PUFA). After 4 wk feeding of the experimental diets, hens were implanted with wing vein catheters and injected with porcine glucagon (20 microg/kg BW) and porcine insulin (0.5 IU/kg BW), 2 to 5 h after oviposition. Plasma glucose, TG, and TG-rich lipoprotein concentrations were determined from 10 min pre-injection to 60 min post-injection. PO diet resulted in a prolonged plasma glucose response to glucagon administration and altered hypoglycemic response to insulin. However, CO diet did not influence plasma glucose response to either glucagon or insulin administration compared to LF diet. The effects of glucagon and insulin on plasma TG and TG-rich lipoproteins were similar for all diets regardless of the amount or type of fat. The results suggest that feeding dietary fats with high n-6 to n-3 PUFA ratio alters the glucagon and insulin sensitivity of plasma glucose in laying hens. Fats rich in n-3 PUFA seem to have no influence on the plasma glucose response to glucagon and insulin. PMID:12455597

  7. Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-activated protein kinase.

    PubMed

    Hwang, Seung-Lark; Yang, Byung-Keun; Lee, Jai-Youl; Kim, Jeong-Han; Kim, Byung-Dong; Kim, Byung-Hong; Suh, Ki-Hyoung; Kim, Dae Young; Kim, Dae-Yong; Kim, Moon Sung; Song, Hebok; Park, Byeoung-Soo; Huh, Tae-Lin

    2008-06-27

    AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is implicated as a key factor in controlling whole body homeostasis, including fatty acid oxidation and glucose uptake. We report that a synthetic structural isomer of dihydrocapsiate, isodihydrocapsiate (8-methylnonanoic acid 3-hydroxy-4-methoxy benzyl ester) improves type 2 diabetes by activating AMPK through the LKB1 pathway. In L6 myotube cells, phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and glucose uptake were significantly increased, whereas these effects were attenuated by an AMPK inhibitor, compound C. In addition, increased phosphorylation of AMPK and ACC by isodihydrocapsiate was significantly reduced by radicicol, an LKB1 destabilizer, suggesting that increased glucose uptake in L6 cells with isodihydrocapsiate treatment is predominantly accomplished by a LKB1-mediated AMPK activation pathway. Oral administration of isodihydrocapsiate to diabetic (db/db) mice reduced blood glucose levels by 40% after a 4-week treatment period. Our results support the development of isodihydrocapsiate as a potential therapeutic agent to target AMPK in type 2 diabetes. PMID:18435912

  8. Enhancement of glucose uptake in skeletal muscle L6 cells and insulin secretion in pancreatic hamster-insulinoma-transfected cells by application of non-thermal plasma jet

    NASA Astrophysics Data System (ADS)

    Kumar, Naresh; Kaushik, Nagendra K.; Park, Gyungsoon; Choi, Eun H.; Uhm, Han S.

    2013-11-01

    Type-II diabetes Mellitus is characterized by defects in insulin action on peripheral tissues, such as skeletal muscle, adipose tissue, and liver and pancreatic beta cells. Since the skeletal muscle accounts for approximately 75% of insulin-stimulated glucose-uptake in our body, impaired insulin secretion from defected beta cell plays a major role in the afflicted glucose homoeostasis. It was shown that the intracellular reactive oxygen species and nitric oxide level was increased by non-thermal-plasma treatment in ambient air. These increased intracellular reactive species may enhance glucose uptake and insulin secretion through the activation of intracellular calcium (Ca+) and cAMP production.

  9. Consumption of the slow-digesting waxy maize starch leads to blunted plasma glucose and insulin response but does not influence energy expenditure or appetite in humans

    PubMed Central

    Sands, Amanda L.; Leidy, Heather J.; Hamaker, Bruce R.; Maguire, Paul; Campbell, Wayne W.

    2015-01-01

    Limited research in humans suggests that slowly digestible starch may blunt the postprandial increase and subsequent decline of plasma glucose and insulin concentrations, leading to prolonged energy availability and satiety, compared to more rapidly digestible starch. This study examined the postprandial metabolic and appetitive responses of waxy maize starch (WM), a slow-digestible starch. It was hypothesized that the waxy maize treatment would result in a blunted and more sustained glucose and insulin response, as well as energy expenditure and appetitive responses. Twelve subjects (6 men and 6 women) (age, 23 ± 1 years; body mass index, 22.2 ± 0.7 kg/m2; insulin sensitivity [homeostatic model assessment], 16% ± 2%; physical activity, 556 ± 120 min/wk) consumed, on separate days, 50 g of available carbohydrate as WM, a maltodextrin-sucrose mixture (MS), or white bread (control). Postprandial plasma glucose and insulin, energy expenditure, and appetite (hunger, fullness, desire to eat) were measured over 4 hours. Compared to control, the 4-hour glucose response was not different for MS and WM, and the 4-hour insulin response was higher for MS (P < .005) and lower for WM (P < .05). Compared to MS, WM led to lower 4-hour glucose and insulin responses (P < .001). These differences were driven by blunted glucose and insulin responses during the first hour for WM. Postprandial energy expenditure and appetite were not different among treatments. These results support that WM provides sustained glucose availability in young, insulin-sensitive adults. PMID:19628104

  10. The effects of wild blueberry consumption on plasma markers and gene expression related to glucose metabolism in the obese Zucker rat.

    PubMed

    Vendrame, Stefano; Zhao, Alice; Merrow, Thomas; Klimis-Zacas, Dorothy

    2015-06-01

    Impaired fasting blood glucose is one of the landmark signs of metabolic syndrome, together with hyperinsulinemia, dyslipidemia, hypertension, and a chronic proinflammatory, pro-oxidative, and prothrombotic environment. This study investigates the effect of wild blueberry (WB) consumption on blood glucose levels and other parameters involved in glucose metabolism in the obese Zucker rat (OZR), an experimental model of metabolic syndrome. Sixteen OZRs and 16 lean littermate controls (lean Zucker rat [LZR]) were fed an 8% enriched WB diet or a control (C) diet for 8 weeks. Plasma concentrations of glucose, insulin, glycated hemoglobin GHbA1c, resistin, and retinol-binding protein 4 (RBP4) were measured. Expression of the resistin, RBP4, and glucose transporter GLUT4 genes was also determined both in the liver and the abdominal adipose tissue (AAT). Plasma glycated hemoglobin HbA1c, RBP4, and resistin concentrations were significantly lower in OZRs following the WB diet (-20%, -22%, and -27%, respectively, compared to C diet, P<.05). Following WB consumption, resistin expression was significantly downregulated in the liver of both OZRs and LZRs (-28% and -61%, respectively, P<.05), while RBP4 expression was significantly downregulated in the AAT of both OZRs and LZRs (-87% and -43%, respectively, P<.05). All other markers were not significantly affected following WB consumption. In conclusion, WB consumption normalizes some markers related to glucose metabolism in the OZR model of metabolic syndrome, but has no effect on fasting blood glucose or insulin concentrations. PMID:25383490

  11. Consumption of the slow-digesting waxy maize starch leads to blunted plasma glucose and insulin response but does not influence energy expenditure or appetite in humans.

    PubMed

    Sands, Amanda L; Leidy, Heather J; Hamaker, Bruce R; Maguire, Paul; Campbell, Wayne W

    2009-06-01

    Limited research in humans suggests that slowly digestible starch may blunt the postprandial increase and subsequent decline of plasma glucose and insulin concentrations, leading to prolonged energy availability and satiety, compared to more rapidly digestible starch. This study examined the postprandial metabolic and appetitive responses of waxy maize starch (WM), a slow-digestible starch. It was hypothesized that the waxy maize treatment would result in a blunted and more sustained glucose and insulin response, as well as energy expenditure and appetitive responses. Twelve subjects (6 men and 6 women) (age, 23 +/- 1 years; body mass index, 22.2 +/- 0.7 kg/m(2); insulin sensitivity [homeostatic model assessment], 16% +/- 2%; physical activity, 556 +/- 120 min/wk) consumed, on separate days, 50 g of available carbohydrate as WM, a maltodextrin-sucrose mixture (MS), or white bread (control). Postprandial plasma glucose and insulin, energy expenditure, and appetite (hunger, fullness, desire to eat) were measured over 4 hours. Compared to control, the 4-hour glucose response was not different for MS and WM, and the 4-hour insulin response was higher for MS (P < .005) and lower for WM (P < .05). Compared to MS, WM led to lower 4-hour glucose and insulin responses (P < .001). These differences were driven by blunted glucose and insulin responses during the first hour for WM. Postprandial energy expenditure and appetite were not different among treatments. These results support that WM provides sustained glucose availability in young, insulin-sensitive adults. PMID:19628104

  12. Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability

    PubMed Central

    Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

    2014-01-01

    Background and Purpose The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Experimental Approach Four cysteine-modified GLP-1 analogues (1–4) were prepared using Gly8-GLP-1(7–36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Key Results Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Conclusions and Implications Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. PMID:25039358

  13. Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test.

    PubMed

    Berhane, Feven; Fite, Alemu; Daboul, Nour; Al-Janabi, Wissam; Msallaty, Zaher; Caruso, Michael; Lewis, Monique K; Yi, Zhengping; Diamond, Michael P; Abou-Samra, Abdul-Badi; Seyoum, Berhane

    2015-01-01

    Insulin resistance, which plays a central role in the pathogenesis of type 2 diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is imperative to understand the metabolic changes that occur at the cellular level in the early stages of insulin resistance. The objective of this study was to determine the pattern of circulating lactate levels during oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal nondiabetic subjects. Lactate and glycerol were determined every 30 minutes during OGTT and HIEC on 22 participants. Lactate progressively increased throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had significantly higher mean M-values compared to those with BMI ≥ 30 at baseline (P < 0.05). This trend also continued throughout the OGTT. In addition, those with impaired glucose tolerance test (IGT) had significantly higher mean lactate levels compared to those with normal glucose tolerance (P < 0.001). In conclusion, we found that lactate increased during HIEC study, which is a state of hyperinsulinemia similar to the metabolic milieu seen during the early stages in the development of T2D. PMID:25961050

  14. U1h shaft project

    SciTech Connect

    Brian Briggs; R. G. Musick

    2000-06-30

    The U1h shaft project is a design/build subcontract to construct one 20 foot (ft) finished diameter shaft to a depth of 1,045 ft at the Nevada Test Site. Atkinson Construction was subcontracted by Bechtel Nevada to construct the U1h Shaft for the Department of Energy. The project consists of furnishing and installing the sinking plant, construction of the 1,045 ft of concrete lined shaft, development of a shaft station at a depth of 976 ft, and construction of a loading pocket at the station. The outfitting of the shaft and installation of a new hoist may be incorporated into the project at a later date. This paper should be of interest to those involved with the construction of relatively deep shafts and underground excavations.

  15. Metabonomic signature analysis of cervical carcinoma and precancerous lesions in women by (1)H NMR spectroscopy.

    PubMed

    Hasim, Ayshamgul; Ali, Mayinuer; Mamtimin, Batur; Ma, Jun-Qi; Li, Qiao-Zhi; Abudula, Abulizi

    2012-06-01

    (1)H nuclear magnetic resonance (NMR)-based metabonomics has been used to characterize the metabolic profiles of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to model the systematic variation related to patients with CIN or CSCC with healthy controls. Potential metabolic biomarkers were identified using database comparisons, and the one-way analysis of variance (ANOVA) test was used to examine the significance of the metabolites. Compared with plasma obtained from the healthy controls, plasma from patients with CIN had higher levels of very-low density lipoprotein (VLDL), acetone, unsaturated lipid and carnitine, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, glycine, acetylcysteine, myo-inositol, choline and glycoprotein. Plasma from patients with CSCC had higher levels of acetate and formate, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine and tyrosine compared with the plasma of the healthy controls. In addition, compared with the plasma of patients with CIN, the plasma of CSCC patients had higher levels of acetate, formate, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, tyrosine, acetylcysteine, myo-inositol, glycoprotein, α-glucose and β-glucose, together with lower levels of acetone, unsaturated lipid and carnitine. Moreover, the profiles showed high feasibility and specificity by statistical analysis with OPLS-DA compared to the Thinprep cytology test (TCT) by setting the histopathological outcome as standard. The metabolic profile obtained for cervical cancer is significant, even for the precancerous disease. This suggests a systemic metabolic response to cancer, which may be used to identify potential early diagnostic biomarkers of the cancer and to establish

  16. Metabonomic signature analysis of cervical carcinoma and precancerous lesions in women by 1H NMR spectroscopy

    PubMed Central

    HASIM, AYSHAMGUL; ALI, MAYINUER; MAMTIMIN, BATUR; MA, JUN-QI; LI, QIAO-ZHI; ABUDULA, ABULIZI

    2012-01-01

    1H nuclear magnetic resonance (NMR)-based metabonomics has been used to characterize the metabolic profiles of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to model the systematic variation related to patients with CIN or CSCC with healthy controls. Potential metabolic biomarkers were identified using database comparisons, and the one-way analysis of variance (ANOVA) test was used to examine the significance of the metabolites. Compared with plasma obtained from the healthy controls, plasma from patients with CIN had higher levels of very-low density lipoprotein (VLDL), acetone, unsaturated lipid and carnitine, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, glycine, acetylcysteine, myo-inositol, choline and glycoprotein. Plasma from patients with CSCC had higher levels of acetate and formate, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine and tyrosine compared with the plasma of the healthy controls. In addition, compared with the plasma of patients with CIN, the plasma of CSCC patients had higher levels of acetate, formate, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, tyrosine, acetylcysteine, myo-inositol, glycoprotein, α-glucose and β-glucose, together with lower levels of acetone, unsaturated lipid and carnitine. Moreover, the profiles showed high feasibility and specificity by statistical analysis with OPLS-DA compared to the Thinprep cytology test (TCT) by setting the histopathological outcome as standard. The metabolic profile obtained for cervical cancer is significant, even for the precancerous disease. This suggests a systemic metabolic response to cancer, which may be used to identify potential early diagnostic biomarkers of the cancer and to establish

  17. A Linear Dose-Response Relationship between Fasting Plasma Glucose and Colorectal Cancer Risk: Systematic Review and Meta-analysis

    PubMed Central

    Shi, Jianguo; Xiong, Lijuan; Li, Jiaoyuan; Cao, Heng; Jiang, Wen; Liu, Bo; Chen, Xueqin; Liu, Cheng; Liu, Ke; Wang, Guobin; Cai, Kailin

    2015-01-01

    For many years, the question of whether hyperglycaemia, a manifestation of prediabetes, diabetes mellitus and metabolic syndrome, is a risk factor for colorectal cancer has been intensely studied. In fact, even after the conclusion of several prospective studies, the topic is still controversial. We conducted a systematic review and meta-analysis to investigate the dose-response relationship between blood glucose concentration and the incidence of colorectal cancer. A linear (P = 0.303 for non-linearity) dose-response relationship was observed between fasting plasma glucose (FPG) and colorectal cancer risk without significant heterogeneity. The relative risk (RR) for colorectal cancer per 20 mg/dL increase in FPG was 1.015 (95% CI: 1.012–1.019, P = 0.000). In subgroup analyses, the pooled RRs for colon cancer (CC) and rectal cancer (RC) studies were 1.035 (95% CI 1.008–1.062, P = 0.011) and 1.031 (95% CI: 0.189–5.628, P = 0.972), respectively; in the analysis comparing men and women, the pooled RRs were 1.016 (95% CI: 1.012–1.020, P = 0.000) and 1.011 (95% CI: 0.995–1.027, P = 0.164), respectively. Sensitivity analyses using two methods showed similar results. In conclusion, there is a significant linear dose-response relationship between FPG and the incidence risk of colorectal cancer. For people with diabetes or prediabetes, controlling blood glucose might be useful to prevent colorectal cancer. PMID:26620869

  18. Development of diagnotors based on time-average values of plasma glucose and immunoreactive insulin levels during intravenous glucose tolerance testing

    NASA Astrophysics Data System (ADS)

    Denisova, Tatyana P.; Malinov, Igor A.; Malinova, Lidia I.; Brook, Sergey B.

    2000-04-01

    The diagnostic algorithm of glucose-insulinic violations for the patients with a clinically obvious atherosclerosis of coronary arteries, non-insulin dependent diabetes mellitus and persons with the heritable predisposition to these forms of pathology was designed. The realization of intravenous glucose tolerance test in specially fitted groups of patients served as basis of the algorithm.

  19. Deoxyandrographolide promotes glucose uptake through glucose transporter-4 translocation to plasma membrane in L6 myotubes and exerts antihyperglycemic effect in vivo.

    PubMed

    Arha, Deepti; Pandeti, Sukanya; Mishra, Akansha; Srivastava, Swayam Prakash; Srivastava, Arvind Kumar; Narender, Tadigoppula; Tamrakar, Akhilesh Kumar

    2015-12-01

    Skeletal muscle is the principal site for postprandial glucose utilization and augmenting the rate of glucose utilization in this tissue may help to control hyperglycemia associated with diabetes mellitus. Here, we explored the effect of Deoxyandrographolide (DeoAn) isolated from the Andrographis paniculata Nees on glucose utilization in skeletal muscle and investigated its antihyperglycemic effect in vivo in streptozotocin-induced diabetic rats and genetically diabetic db/db mice. In L6 myotubes, DeoAn dose-dependently stimulated glucose uptake by enhancing the translocation of glucose transporter 4 (GLUT4) to cell surface, without affecting the total cellular GLUT4 and GLUT1 content. These effects of DeoAn were additive to insulin. Further analysis revealed that DeoAn activated PI-3-K- and AMPK-dependent signaling pathways, account for the augmented glucose transport in L6 myotubes. Furthermore, DeoAn lowered postprandial blood glucose levels in streptozotocin-induced diabetic rats and also suppressed the rises in the fasting blood glucose, serum insulin, triglycerides and LDL-Cholesterol levels of db/db mice. These findings suggest the therapeutic efficacy of the DeoAn for type 2 diabetes mellitus and can be potential phytochemical for its management. PMID:26528798

  20. Nerve conduction abnormalities in untreated maturity-onset diabetes: relation to levels of fasting plasma glucose and glycosylated hemoglobin.

    PubMed

    Graf, R J; Halter, J B; Halar, E; Porte, D

    1979-03-01

    The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the influence of hyperglycemia on nerve conduction, we studied 20 untreated maturity-onset diabetic patients and 23 normal control subjects of similar age. Nerve conduction velocity of motor (median, peroneal, and tibial) and sensory (median and sural) nerves in diabetic patients was significantly slowed and H-reflex latency time prolonged. Levels of fasting plasma glucose in diabetic subjects were correlated with slowed motor conduction velocity of the median, peroneal, and tibial nerves but not with sensory nerve conduction velocities. Levels of glycosylated hemoglobin, an index of long-term glycemia, were correlated with slowing of peroneal motor conduction velocity in diabetic patients. These associations could not be explained by patient age or duration of diabetes. These findings suggest that the degree of hyperglycemia of untreated maturity-onset diabetes contributes to the motor nerve conduction abnormalities in this disease. PMID:426398

  1. Combination of 5-aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats.

    PubMed

    Hara, Takeshi; Koda, Aya; Nozawa, Naoko; Ota, Urara; Kondo, Hikaru; Nakagawa, Hitoshi; Kamiya, Atsuko; Miyashita, Kazutoshi; Itoh, Hiroshi; Nakajima, Motowo; Tanaka, Tohru

    2016-06-01

    Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2DM). 5-Aminolevulinic acid (ALA), a natural amino acid produced only in the mitochondria, is a precursor of heme. Cytochromes that contain heme play an important role in aerobic energy metabolism. Thus, ALA may help reduce T2DM-associated hyperglycemia. In this study, we investigated the effect of ALA combined with sodium ferrous citrate (SFC) on hyperglycemia in Zucker diabetic fatty (ZDF) rats. We found that the gavage administration of ALA combined with SFC (ALA/SFC) for 6 weeks reduced plasma glucose and hemoglobin A1c (HbA1c) levels in rats without affecting plasma insulin levels. The glucose-lowering effect depended on the amount of ALA/SFC administered per day. Furthermore, the glucose tolerance was also significantly improved by ALA/SFC administration. Although food intake was slightly reduced in the rats administered ALA/SFC, there was no effect on their body weight. Importantly, ALA/SFC administration induced heme oxygenase-1 (HO-1) expression in white adipose tissue and liver, and the induced expression levels of HO-1 correlated with the glucose-lowering effects of ALA/SFC. Taken together, these results suggest that ALA combined with ferrous ion is effective in reducing hyperglycemia of T2DM without affecting plasma insulin levels. HO-1 induction may be involved in the mechanisms underlying the glucose-lowering effect of ALA/SFC. PMID:27239432

  2. The effects of a nutraceutical combination on plasma lipids and glucose: A systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Pirro, Matteo; Mannarino, Massimo Raffaele; Bianconi, Vanessa; Simental-Mendía, Luis E; Bagaglia, Francesco; Mannarino, Elmo; Sahebkar, Amirhossein

    2016-08-01

    Dyslipidemia and hyperglycemia are associated with an increased risk of ischemic cardiovascular disease. Positive effects of a nutraceutical combination comprising red yeast rice, berberine, policosanol, astaxanthin, coenzyme Q10 and folic acid (NComb) on plasma lipid and glucose levels have been reported in some but not all clinical trials. To address this inconsistency, we tried to estimate the size of lipid- and glucose-lowering effects of NComb through a systematic review and meta-analysis of randomized controlled trials. A systematic literature search in PubMed-Medline, SCOPUS and Google Scholar databases was conducted to identify randomized controlled trials investigating the effects of NComb on plasma lipids and glucose levels. Inverse variance-weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in lipid and glucose levels using a random-effects model. Random-effects meta-regression was performed to assess the effect of putative confounders on plasma lipid and glucose levels. Fourteen trials (1670 subjects in the NComb arm and 1489 subjects in the control arm) met the eligibility criteria for lipid analysis and 10 trials (1014 subjects in the NComb arm and 962 subjects in the control arm) for glucose analysis. Overall, WMDs were significant for the impact of NComb supplementation on plasma levels of total cholesterol (-26.15mg/dL, p<0.001), LDL-cholesterol (-23.85mg/dL, p<0.001), HDL-cholesterol (2.53mg/dL, p<0.001), triglycerides (-13.83mg/dL, p<0.001) and glucose (-2.59mg/dL, p=0.010). NComb-induced amelioration of lipid profile was not affected by duration of supplementation nor by baseline lipid levels; conversely, a greater glucose-lowering effect of NComb was found with higher baseline glucose levels and longer durations of supplementation. In conclusion, the present results suggest that NComb supplementation is associated with improvement of lipid and glucose profile. Short-term beneficial effects of

  3. Comparison of the clinical characteristics of diabetes mellitus diagnosed using fasting plasma glucose and haemoglobin A1c: The 2011 Korea National Health and Nutrition Examination Survey.

    PubMed

    Hong, Sangmo; Kang, Jun Goo; Kim, Chul Sik; Lee, Seong Jin; Lee, Chang Beom; Ihm, Sung-Hee

    2016-03-01

    We compared the characteristics of a Korean adult population diagnosed with diabetes using only a fasting plasma glucose criterion or an HbA1c criterion. The single difference between these two groups was age. Further studies should be undertaken to clarify whether age-specific diagnostic criteria would be appropriate in Korean populations. PMID:26972956

  4. Mass spectrometry-based microassay of (2)H and (13)C plasma glucose labeling to quantify liver metabolic fluxes in vivo.

    PubMed

    Hasenour, Clinton M; Wall, Martha L; Ridley, D Emerson; Hughey, Curtis C; James, Freyja D; Wasserman, David H; Young, Jamey D

    2015-07-15

    Mouse models designed to examine hepatic metabolism are critical to diabetes and obesity research. Thus, a microscale method to quantitatively assess hepatic glucose and intermediary metabolism in conscious, unrestrained mice was developed. [(13)C3]propionate, [(2)H2]water, and [6,6-(2)H2]glucose isotopes were delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on three 40-μl arterial plasma glucose samples obtained during the euglycemic isotopic steady state. Model-based regression of hepatic glucose and citric acid cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model to track carbon and hydrogen atom transitions through the network and thereby simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from glycogen diminished, and endogenous glucose production was exclusively gluconeogenic with prolonged fasting. Gluconeogenic flux from phosphoenolpyruvate (PEP) remained stable, whereas that from glycerol modestly increased from short- to long-term fasting. CAC flux [i.e., citrate synthase (VCS)] was reduced with long-term fasting. Interestingly, anaplerosis and cataplerosis increased with fast duration; accordingly, pyruvate carboxylation and the conversion of oxaloacetate to PEP were severalfold higher than VCS in long-term fasted mice. This method utilizes state-of-the-art in vivo methodology and comprehensive isotopomer modeling to quantify hepatic glucose and intermediary fluxes during physiological stress in mice. The small plasma requirements permit serial sampling without stress and the affirmation of steady-state glucose kinetics. Furthermore, the approach can accommodate a broad range of modeling assumptions, isotope tracers, and measurement inputs without the need to introduce ad hoc mathematical approximations. PMID:25991647

  5. Multiple-Input Subject-Specific Modeling of Plasma Glucose Concentration for Feedforward Control

    PubMed Central

    2015-01-01

    The ability to accurately develop subject-specific, input causation models, for blood glucose concentration (BGC) for large input sets can have a significant impact on tightening control for insulin dependent diabetes. More specifically, for Type 1 diabetics (T1Ds), it can lead to an effective artificial pancreas (i.e., an automatic control system that delivers exogenous insulin) under extreme changes in critical disturbances. These disturbances include food consumption, activity variations, and physiological stress changes. Thus, this paper presents a free-living, outpatient, multiple-input, modeling method for BGC with strong causation attributes that is stable and guards against overfitting to provide an effective modeling approach for feedforward control (FFC). This approach is a Wiener block-oriented methodology, which has unique attributes for meeting critical requirements for effective, long-term, FFC. PMID:25620845

  6. Effect of altered eating pattern on serum fructosamine: total protein ratio and plasma glucose level.

    PubMed

    Ch'ng, S L; Cheah, S H; Husain, R; Duncan, M T

    1989-05-01

    The effect of alteration of eating pattern during Ramadan on body mass index (BMI), serum fructosamine: total protein ratio (F/TP), and glucose level in 18 healthy male Asiatic Moslems were studied. The results showed a significant decrease (p less than 0.025) in F/TP at the second week of Ramadan in 11 subjects who experienced continuous decrease in BMI throughout Ramadan. The remaining 7 subjects showed no significant changes in BMI and F/TP. No evidence of hypoglycaemia was observed in the subjects during the study. Serum fructosamine: total protein ratio in subjects with altered eating pattern preferably should be interpreted along with the change in body mass index. PMID:2774480

  7. Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice

    PubMed Central

    Stanley, Sarah A.; Gagner, Jennifer E.; Damanpour, Shadi; Yoshida, Mitsukuni; Dordick, Jonathan S.; Friedman, Jeffrey M.

    2013-01-01

    Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca2+-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells. PMID:22556257

  8. Glucose transport and milk secretion during manipulated plasma insulin and glucose concentrations and during LPS-induced mastitis in dairy cows.

    PubMed

    Gross, J J; van Dorland, H A; Wellnitz, O; Bruckmaier, R M

    2015-08-01

    In dairy cows, glucose is essential as energy source and substrate for milk constituents. The objective of this study was to investigate effects of long-term manipulated glucose and insulin concentrations in combination with a LPS-induced mastitis on mRNA abundance of glucose transporters and factors involved in milk composition. Focusing on direct effects of insulin and glucose without influence of periparturient endocrine adaptations, 18 dairy cows (28 ± 6 weeks of lactation) were randomly assigned to one of three infusion treatments for 56 h (six animals each). Treatments included a hyperinsulinemic hypoglycaemic clamp (HypoG), a hyperinsulinemic euglycaemic clamp (EuG) and a control group (NaCl). After 48 h of infusions, an intramammary challenge with LPS from E. coli was performed and infusions continued for additional 8 h. Mammary gland biopsies were taken before, at 48 (before LPS challenge) and at 56 h (after LPS challenge) of infusion, and mRNA abundance of genes involved in mammary gland metabolism was measured by RT-qPCR. During the 48 h of infusions, mRNA abundance of glucose transporters GLUT1, 3, 4, 8, 12, SGLT1, 2) was not affected in HypoG, while they were downregulated in EuG. The mRNA abundance of alpha-lactalbumin, insulin-induced gene 1, κ-casein and acetyl-CoA carboxylase was downregulated in HypoG, but not affected in EuG. Contrary during the intramammary LPS challenge, most of the glucose transporters were downregulated in NaCl and HypoG, but not in EuG. The mRNA abundance of glucose transporters in the mammary gland seems not to be affected by a shortage of glucose, while enzymes and milk constituents directly depending on glucose as a substrate are immediately downregulated. During LPS-induced mastitis in combination with hypoglycaemia, mammary gland metabolism was more aligned to save glucose for the immune system compared to a situation without limited glucose availability during EuG. PMID:25319117

  9. Effects of pentobarbital on plasma glucose and free fatty acids in the rat.

    NASA Technical Reports Server (NTRS)

    Furner, R. L.; Neville, E. D.; Talarico, K. S.; Feller, D. D.

    1972-01-01

    Hyperglycemia and hypolipemia were observed in rats after the injection of sodium pentobarbital. The observed changes were independent of whether the blood was collected by decapitation or by needle puncture of the aorta. The hyperglycemic response was caused by two factors including the stress of the injection per se and the pharmacological action of the drug. Hyperlipemia was observed at 5 min postinjection. However, pentobarbital decreased plasma free fatty acids by 15 min postinjection. Both the hyperglycemia and hypolipemia responses were dose dependent.

  10. Plasma secretin concentration in anaesthetized pigs after intraduodenal glucose, fat, aminoacids, or meals with various pH.

    PubMed

    Fahrenkrug, J; Schaffalitzky de Muckadell, O B; Holst, J J

    1977-01-01

    The concentration of immunoreactive secretin in portal blood and the secretion from the exocrine pancreas were measured during intraduodenal infusion of isotonic or hypertonic saline, isotonic or hypertonic glucose, aminoacids, fat emulsion, or 0.1 mol X 1(-1) hydrochloric acid in 7 anaesthetized pigs. None of these substances, except hydrochloric acid, had any effect on plasma secretin concentration and pancreatic flow rate and bicarbonate output. Plasma secretin concentration rose significantly from 5.6 +/- 2.7 pmol X 1(-1) (mean +/- S.E.M.) to a peak value of 201.2 +/- 80.5 pmol X 1(-1) 15 min after infusion of hydrochloric acid. Pancreatic flow rate and bicarbonate output increased from 0.51 +/- 0.19 ml X h-1 (mean +/- S.E.M.) to 9.85 +/- 2.33 ml X h-1 and from 52 +/- 11 micronmol X h-1 to 1.004 +/- 290 micronmol X h-1, respectively. During intraduodenal introduction of meals with pH adjusted from 1.0 to 7.0 in 4 pigs amylase was secreted at all pH levels. However, only when pH of the meal was 1.0, resulting in an intraduodenal pH from 1.0 to 1.7 during the stimulation, was a significant increase in plasma secretin concentration and pancreatic flow rate observed from 5.5 +/- 2.8 pmol X 1(-1) (mean +/- S.E.M.) to 115.0 +/- 51.2 pmol X 1(-1) and from 0.20 +/- 0.08 ml X h-1 to 6.25 +/- 2.57 ml X h-1, respectively. PMID:17153

  11. γ-Tocopherol abolishes postprandial increases in plasma methylglyoxal following an oral dose of glucose in healthy, college-aged men.

    PubMed

    Masterjohn, Christopher; Mah, Eunice; Guo, Yi; Koo, Sung I; Bruno, Richard S

    2012-03-01

    Postprandial hyperglycemia contributes to the risk of cardiovascular disease in part by increasing concentrations of the reactive dicarbonyl methylglyoxal (MGO), a byproduct of glucose metabolism. Oxidative stress increases MGO formation from glucose in vitro and decreases its glutathione-dependent detoxification to lactate. We hypothesized that the antioxidant γ-tocopherol, a form of vitamin E, would decrease hyperglycemia-mediated postprandial increases in plasma MGO in healthy, normoglycemic, college-aged men. Participants (n=12 men; 22.3±1.0 years; 29.3±2.4 kg/m(2)) received an oral dose of glucose (75 g) in the fasted state prior to and following 5-day ingestion of a vitamin E supplement enriched in γ-tocopherol (500 mg/day). γ-Tocopherol supplementation increased (P<.0001) plasma γ-tocopherol from 2.22±0.32 to 7.06±0.71 μmol/l. Baseline MGO concentrations and postprandial hyperglycemic responses were unaffected by γ-tocopherol supplementation (P>.05). Postprandial MGO concentrations increased in the absence of supplemental γ-tocopherol (P<.05), but not following γ-tocopherol supplementation (P>.05). Area under the curve for plasma MGO was significantly (P<.05) smaller with the supplementation of γ-tocopherol than without (area under the curve (0-180 min), -778±1010 vs. 2277±705). Plasma concentrations of γ-carboxyethyl-hydroxychroman, reduced glutathione and markers of total antioxidant capacity increased after supplementation, and these markers and plasma γ-tocopherol were inversely correlated with plasma MGO (r=-0.48 to -0.67, P<.05). These data suggest that short-term supplementation of γ-tocopherol abolishes the oral glucose-mediated increases in postprandial MGO through its direct and indirect antioxidant properties and may reduce hyperglycemia-mediated cardiovascular disease risk. PMID:21543210

  12. Changes in Plasma Levels of N-Arachidonoyl Ethanolamine and N-Palmitoylethanolamine following Bariatric Surgery in Morbidly Obese Females with Impaired Glucose Homeostasis

    PubMed Central

    Mallipedhi, Akhila; Prior, Sarah L.; Dunseath, Gareth; Bracken, Richard M.; Barry, Jonathan; Caplin, Scott; Eyre, Nia; Morgan, James; Baxter, John N.; O'Sullivan, Saoirse E.; Sarmad, Sarir; Barrett, David A.; Bain, Stephen C.; Luzio, Steve D.

    2015-01-01

    Aim. We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods. A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results. Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = −0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = −0.59, P = 0.04). Conclusion. Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis. PMID:25874237

  13. 1H NMR global metabolic phenotyping of acute pancreatitis in the emergency unit.

    PubMed

    Villaseñor, Alma; Kinross, James M; Li, Jia V; Penney, Nicholas; Barton, Richard H; Nicholson, Jeremy K; Darzi, Ara; Barbas, Coral; Holmes, Elaine

    2014-12-01

    We have investigated the urinary and plasma metabolic phenotype of acute pancreatitis (AP) patients presenting to the emergency room at a single center London teaching hospital with acute abdominal pain using (1)H NMR spectroscopy and multivariate modeling. Patients were allocated to either the AP (n = 15) or non-AP patients group (all other causes of abdominal pain, n = 21) on the basis of the national guidelines. Patients were assessed for three clinical outcomes: (1) diagnosis of AP, (2) etiology of AP caused by alcohol consumption and cholelithiasis, and (3) AP severity based on the Glasgow score. Samples from AP patients were characterized by high levels of urinary ketone bodies, glucose, plasma choline and lipid, and relatively low levels of urinary hippurate, creatine and plasma-branched chain amino acids. AP could be reliably identified with a high degree of sensitivity and specificity (OPLS-DA model R(2) = 0.76 and Q(2)Y = 0.59) using panel of discriminatory biomarkers consisting of guanine, hippurate and creatine (urine), and valine, alanine and lipoproteins (plasma). Metabolic phenotyping was also able to distinguish between cholelithiasis and colonic inflammation among the heterogeneous non-AP group. This work has demonstrated that combinatorial biomarkers have a strong diagnostic and prognostic potential in AP with relevance to clinical decision making in the emergency unit. PMID:25160714

  14. Combining glycosylated hemoglobin A1c and fasting plasma glucose for diagnosis of type 2 diabetes in Chinese adults

    PubMed Central

    2013-01-01

    Background Glycosylated hemoglobin A1c (HbA1c) has been applied to identify type 2 diabetes (T2DM) in the U.S. and European countries. It has not been used in China mainly due to lack of a standardized approach to measure HbA1c, short of knowledge about racial-specific standard and deficiency of an optimal cut-off point. Methods To evaluate combination of HbA1c and fasting plasma glucose (FPG) in diagnosing T2DM in Chinese adults, a multistage sampling cross-sectional study was conducted in Shanghai, China, in 2009. The FPG measurement, HbA1c assay, and oral glucose tolerance test (OGTT) were performed in 6,661 Chinese adults (3057 men, 3604 women) who had no prior history of diabetes to identify the unrecognized T2DM. Results A total of 454 participants were identified as T2DM based on the 1999 World Health Organization (WHO) diagnostic criteria. Of these patients, 239 were detected using an FPG ≥ 7.0 mmol/l and 141 were further identified using an HbA1c ≥ 43 mmol/mol (6.1%), achieving a sensitivity of 83.7% and a specificity of 89.3% for combining use of FPG and HbA1c. In subjects at high risk of diabetes, the combining use of FPG and HbA1c produced a higher sensitivity and an improved positive predictive value (PPV), and had a satisfactory specificity and negative predictive value (NPV). Conclusions The combining use of FPG and HbA1c is a potential screening and diagnosis approach for T2DM in Chinese adults, especially among those at high risk of the disease. PMID:24099651

  15. Investigating the Role of Plasma Glucose Concentration as a Phenotypic Marker for CYP2C9 Genetic Variants, in the Diabetic Population of Gujarat.

    PubMed

    Bhatt, D; Chauhan, N; Sharma, A; Dhawan, D; Bhatt, R V; Phatak, S; Padh, H

    2014-01-01

    The present study was aimed to investigate the role of plasma glucose concentration as a phenotypic marker and to study the frequency distribution of CYP2C9 genetic variants in Gujarat state diabetic population. One hundred and nine unrelated diabetes mellitus patients treated with sulfonylureas were genotyped for CYP2C9*2 and CYP2C9*3 alleles. Their pre- and posttreatment postprandial blood glucose levels were recorded and mean glucose drop per milligram of drug values were calculated and further used as an index for phenotypic correlation. The frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles in the Gujarat state diabetic population were 0.84, 0.07 and 0.09, respectively. The distribution of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes were 0.73, 0.08, 0.13, 0.0, 0.06 and 0.0, respectively. Patients with CYP2C9*1/*2 genotype did not show any significant difference in the mean glucose drop per milligram of drug values when compared with wild-type patients in glipizide-treatment group. Patients with CYP2C9*1/*3 genotype showed greater mean glucose drop per milligram of drug values than patients with CYP2C9*1/*1 wild-type genotype for both glipizide and glimepiride while patients with CYP2C9*2/*3 genotype showed greater drop than patients with CYP2C9*1/*1 genotype only in the glipizide-treatment group. The presence of CYP2C9*3 allele significantly affected plasma glucose drop per milligram of drug values in patients taking glipizide and glimepiride, while effects of CYP2C9*2 allele were insignificant. Further studies are needed to confirm the effects of CYP2C9*2 allele on plasma glucose drop per milligram of drug values. However, plasma glucose concentration is a complex physiological marker that cannot be used to establish perfect genotype-phenotype correlation. Hence studies exploring robust phenotypic markers must be initiated. PMID:24799741

  16. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

    PubMed Central

    Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  17. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration.

    PubMed

    Karnchanasorn, Rudruidee; Huang, Jean; Ou, Horng-Yih; Feng, Wei; Chuang, Lee-Ming; Chiu, Ken C; Samoa, Raynald

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m(2), P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  18. Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients☆

    PubMed Central

    Marquis-Gravel, Guillaume; Hayami, Douglas; Juneau, Martin; Nigam, Anil; Guilbeault, Valérie; Latour, Élise; Gayda, Mathieu

    2015-01-01

    Objectives To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and β-cell function in obese subjects. Methods The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and β-cell function of 72 obese subjects (54 women; mean age = 53 ± 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2–3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. Results Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 ± 0.9; after: 5.2 ± 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 ± 57; after: 82 ± 43; P = 0.003), and insulin resistance, as assessed by the HOMA-IR score (before: 3.6 ± 2.5; after: 2.8 ± 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 ± 0.55; after: 5.69 ± 0.39; P = 0.448), nor β-cell function (HOMA-β, %) (before: 149 ± 78; after: 144 ± 75; P = 0.58). Conclusion Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects. PMID:26844086

  19. The Effects of Hyperhydrating Supplements Containing Creatine and Glucose on Plasma Lipids and Insulin Sensitivity in Endurance-Trained Athletes.

    PubMed

    Polyviou, Thelma P; Pitsiladis, Yannis P; Celis-Morales, Carlos; Brown, Benjamin; Speakman, John R; Malkova, Dalia

    2015-01-01

    The addition of carbohydrate (CHO) in the form of simple sugars to creatine (Cr) supplements is central. The study aimed to determine whether ingestion of glucose (Glu) simultaneously with Cr and glycerol (Cr/Gly) supplement is detrimental to plasma lipids of endurance-trained individuals and find out whether modification arising can be attenuated by replacing part of the Glu with alpha lipoic acid (Ala). Twenty-two endurance-trained cyclists were randomized to receive Cr/Gly/Glu (11.4 g Cr-H2O, 1 g Gly/kg BM, and 150 g Glu) or Cr/Gly/Glu/Ala (11.4 g Cr-H2O, 1 g Gly/kg BM, 100 g Glu, and 1 g Ala) for 7 days. Fasting concentration of TAG increased significantly (P < 0.01) after supplementation with Cr/Gly/Glu (before: 0.9 ± 0.2 mmol/L; after: 1.3 ± 0.4 mmol/L) and Cr/Gly/Glu/Ala (before: 0.8 ± 0.2 mmol/L; after: 1.2 ± 0.5 mmol/L) but changes were not different between the groups. Supplementation significantly (P < 0.05) increased the TAG to HDL-cholesterol ratio but had no effect on fasting concentration of total, HDL-, and LDL-cholesterol and insulin resistance. Thus, addition of Glu to Cr containing supplements enhances plasma TAG concentration and the TAG to HDL-cholesterol ratio and this enhancement cannot be attenuated by partial replacement of Glu with Ala. PMID:26167296

  20. The Effects of Hyperhydrating Supplements Containing Creatine and Glucose on Plasma Lipids and Insulin Sensitivity in Endurance-Trained Athletes

    PubMed Central

    Polyviou, Thelma P.; Pitsiladis, Yannis P.; Celis-Morales, Carlos; Brown, Benjamin; Speakman, John R.; Malkova, Dalia

    2015-01-01

    The addition of carbohydrate (CHO) in the form of simple sugars to creatine (Cr) supplements is central. The study aimed to determine whether ingestion of glucose (Glu) simultaneously with Cr and glycerol (Cr/Gly) supplement is detrimental to plasma lipids of endurance-trained individuals and find out whether modification arising can be attenuated by replacing part of the Glu with alpha lipoic acid (Ala). Twenty-two endurance-trained cyclists were randomized to receive Cr/Gly/Glu (11.4 g Cr-H2O, 1 g Gly/kg BM, and 150 g Glu) or Cr/Gly/Glu/Ala (11.4 g Cr-H2O, 1 g Gly/kg BM, 100 g Glu, and 1 g Ala) for 7 days. Fasting concentration of TAG increased significantly (P < 0.01) after supplementation with Cr/Gly/Glu (before: 0.9 ± 0.2 mmol/L; after: 1.3 ± 0.4 mmol/L) and Cr/Gly/Glu/Ala (before: 0.8 ± 0.2 mmol/L; after: 1.2 ± 0.5 mmol/L) but changes were not different between the groups. Supplementation significantly (P < 0.05) increased the TAG to HDL-cholesterol ratio but had no effect on fasting concentration of total, HDL-, and LDL-cholesterol and insulin resistance. Thus, addition of Glu to Cr containing supplements enhances plasma TAG concentration and the TAG to HDL-cholesterol ratio and this enhancement cannot be attenuated by partial replacement of Glu with Ala. PMID:26167296

  1. Crystallographic and computational studies on 4-phenyl-N-(beta-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: comparison with alpha-D-glucose, N-acetyl-beta-D-glucopyranosylamine and N-benzoyl-N'-beta-D-glucopyranosyl urea binding.

    PubMed

    Alexacou, Kyra-Melinda; Hayes, Joseph M; Tiraidis, Costas; Zographos, Spyros E; Leonidas, Demetres D; Chrysina, Evangelia D; Archontis, Georgios; Oikonomakos, Nikos G; Paul, Jashuva V; Varghese, Babu; Loganathan, Duraikkannu

    2008-05-15

    4-Phenyl-N-(beta-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide (glucosyltriazolylacetamide) has been studied in kinetic and crystallographic experiments with glycogen phosphorylase b (GPb), in an effort to utilize its potential as a lead for the design of potent antihyperglycaemic agents. Docking and molecular dynamics (MD) calculations have been used to monitor more closely the binding modes in operation and compare the results with experiment. Kinetic experiments in the direction of glycogen synthesis showed that glucosyltriazolylacetamide is a better inhibitor (K(i) = 0.18 mM) than the parent compound alpha-D-glucose (K(i) = 1.7 mM) or beta-D-glucose (K(i) = 7.4 mM) but less potent inhibitor than the lead compound N-acetyl-beta-D-glucopyranosylamine (K(i) = 32 microM). To elucidate the molecular basis underlying the inhibition of the newly identified compound, we determined the structure of GPb in complex with glucosyltriazolylacetamide at 100 K to 1.88 A resolution, and the structure of the compound in the free form. Glucosyltriazolylacetamide is accommodated in the catalytic site of the enzyme and the glucopyranose interacts in a manner similar to that observed in the GPb-alpha-D-glucose complex, while the substituent group in the beta-position of the C1 atom makes additional hydrogen bonding and van der Waals interactions to the protein. A bifurcated donor type hydrogen bonding involving O3H, N3, and N4 is seen as an important structural motif strengthening the binding of glucosyltriazolylacetamide with GP which necessitated change in the torsion about C8-N2 bond by about 62 degrees going from its free to the complex form with GPb. On binding to GP, glucosyltriazolylacetamide induces significant conformational changes in the vicinity of this site. Specifically, the 280s loop (residues 282-288) shifts 0.7 to 3.1 A (CA atoms) to accommodate glucosyltriazolylacetamide. These conformational changes do not lead to increased contacts between the inhibitor and the

  2. High Fasting Plasma Glucose Mortality Effect: A Comparative Risk Assessment in 25–64 Years Old Iranian Population

    PubMed Central

    Peykari, Niloofar; Saeedi, Moghaddam Sahar; Djalalinia, Shirin; Kasaeian, Amir; Sheidaei, Ali; Mansouri, Anita; Mohammadi, Younes; Parsaeian, Mahboubeh; Mehdipour, Parinaz; Larijani, Bagher; Farzadfar, Farshad

    2016-01-01

    Background: High fasting plasma glucose (FPG) is one of the main leading risk factors of ischemic heart disease (IHD), stroke, and chronic kidney diseases (CKDs). We estimated population attributable fraction (PAF) and attributed death of these fatal outcomes of high FPG at national and subnational levels in 25–64 years old Iranian adult. Methods: We used national and subnational data of the Non-Communicable Disease Surveillance Survey for exposure to risk factors in 2005 and 2011 among Iranian adults of 25–64 years old. For estimating the attributed death, using the death registration system data of Iran, we multiply the cause-specific PAFs by the number of outcome-specific deaths. Results: In Iran, high FPG was responsible for about 31% of attributed total deaths of IHD, stroke, and CKD in 2011. The related attributed deaths had increased from 2005 to 2011. In females, the PAFs for the effect of high FPG on IHD, stroke, and CKD were higher in 2011 than 2005 in all age groups. In males, this increase has occurred in over 45 years old. The highest PAFs of high FPG outcomes mostly related to central provinces of Iran. The central region of Iran had the highest and the southeast of the country had the lowest levels of attributed deaths. Conclusions: Considering the global 25 × 25 targets for noncommunicable disease mortality reduction, high FPG as a leading risk factor of fatal outcomes should be more targeted through the dietary, behavioral, and pharmacological interventions in Iran. PMID:27280011

  3. Stalk segment 5 of the yeast plasma membrane H(+)-ATPase. Labeling with a fluorescent maleimide reveals a conformational change during glucose activation.

    PubMed

    Miranda, Manuel; Pardo, Juan Pablo; Allen, Kenneth E; Slayman, Carolyn W

    2002-10-25

    Glucose is well known to cause a rapid, reversible activation of the yeast plasma membrane H(+)-ATPase, very likely mediated by phosphorylation of two or more Ser/Thr residues near the C terminus. Recent mutagenesis studies have shown that glucose-dependent activation can be mimicked constitutively by amino acid substitutions in stalk segment 5 (S5), an alpha-helical stretch connecting the catalytic part of the ATPase with transmembrane segment 5 (Miranda, M., Allen, K. E., Pardo, J. P., and Slayman, C. W. (2001) J. Biol. Chem. 276, 22485-22490). In the present work, the fluorescent maleimide Alexa-488 has served as a probe for glucose-dependent changes in the conformation of S5. Experiments were carried out in a "3C" version of the ATPase, from which six of nine native cysteines had been removed by site-directed mutagenesis to eliminate background labeling by Alexa-488. In this construct, three of twelve cysteines introduced at various positions along S5 (A668C, S672C, and D676C) reacted with the Alexa dye in a glucose-independent manner, as shown by fluorescent labeling of the 100 kDa Pma1 polypeptide and by isolation and identification of the corresponding tryptic peptides. Especially significant was the fact that three additional cysteines reacted with Alexa-488 more rapidly (Y689C) or only (V665C and L678C) in plasma membranes from glucose-metabolizing cells. The results support a model in which the S5 alpha-helix undergoes a significant change in conformation to expose positions 665, 678, and 689 during glucose-dependent activation of the ATPase. PMID:12169695

  4. Glucose-β-CD interaction assisted ACN field-amplified sample stacking in CZE for determination of trace amlodipine in beagle dog plasma.

    PubMed

    Li, Ji; Li, You; Zhang, Wenting; Chen, Zhao; Fan, Guorong

    2013-06-01

    A simple, sensitive and low-cost method using CE coupled with glucose-β-CD interaction assisted ACN stacking technique has been developed for quantification of trace amlodipine in dog plasma. The plasma samples were extracted with methyl tert-butyl ether. The separation was performed at 25°C in a 31.2 cm × 75 μm fused-silica capillary with an applied voltage of 15 kV. The BGE was composed of 6.25 mM borate/25 mM phosphate (pH 2.5) and 5 mg/mL glucose-β-CD. The detection wavelength was 200 nm. Because CD could diminish the interaction between drugs and matrix, and derivation groups of CD play an important role in separation performance, the effects of β-CD, and its derivatives on the separation were studied at several concentrations (0, 2.5, 5.0, 10.0 mg/mL). In this study, organic solvent field-amplified sample stacking technique in combination with glucose-β-CD enhanced the sensitivity about 60-70 folds and glucose-β-CD could effectively improve the peak shape. All the validation data, such as accuracy, precision extraction recovery, and stability, were within the required limits. The calibration curve was linear for amlodipine from 1 to 200 ng/mL. The method developed was successfully applied to the pharmacokinetic studies of amlodipine besylate in beagle dogs. PMID:23495256

  5. A mixture of Salacia oblonga extract and IP-PA1 reduces fasting plasma glucose (FPG) and low-density lipoprotein (LDL) cholesterol levels.

    PubMed

    Nakata, Kazue; Taniguchi, Yoshie; Yoshioka, Noriko; Yoshida, Aya; Inagawa, Hiroyuki; Nakamoto, Takeru; Yoshimura, Hiroshi; Miyake, Shin-Ichiro; Kohchi, Chie; Kuroki, Masahide; Soma, Gen-Ichiro

    2011-10-01

    At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of α-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. SI tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG ≥ 150 mg/dl, or LDL ≥ 120 mg/dl, or HDL < 40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases. PMID:22125681

  6. A mixture of Salacia oblonga extract and IP-PA1 reduces fasting plasma glucose (FPG) and low-density lipoprotein (LDL) cholesterol levels

    PubMed Central

    Nakata, Kazue; Taniguchi, Yoshie; Yoshioka, Noriko; Yoshida, Aya; Inagawa, Hiroyuki; Nakamoto, Takeru; Yoshimura, Hiroshi; Miyake, Shin-ichiro; Kohchi, Chie; Kuroki, Masahide

    2011-01-01

    At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of α-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. SI tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG ≥ 150 mg/dl, or LDL ≥ 120 mg/dl, or HDL < 40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases. PMID:22125681

  7. The seasonal glucocorticoid response of male Rufous-winged Sparrows to acute stress correlates with changes in plasma uric acid, but neither glucose nor testosterone.

    PubMed

    Deviche, Pierre; Valle, Shelley; Gao, Sisi; Davies, Scott; Bittner, Stephanie; Carpentier, Elodie

    2016-09-01

    We sought to clarify functional relationships between baseline and acute stress-induced changes in plasma levels of the stress hormone corticosterone (CORT) and the reproductive hormone testosterone (T), and those of two main metabolites, uric acid (UA) and glucose (GLU). Acute stress in vertebrates generally stimulates the secretion of glucocorticoids, which in birds is primarily CORT. This stimulation is thought to promote behavioral and metabolic changes, including increased glycemia. However, limited information in free-ranging birds supports the view that acutely elevated plasma CORT stimulates glycemia. Acute stress also often decreases the secretion of reproductive hormones (e.g., T in males), but the role of CORT in this decrease and the contribution of T to the regulation of plasma GLU remain poorly understood. We measured initial (pre-stress) and acute stress-induced plasma CORT and T as well as GLU in adult male Rufous-winged Sparrows, Peucaea carpalis, sampled during the pre-breeding, breeding, post-breeding molt, and non-breeding stages. Stress increased plasma CORT and the magnitude of this increase did not differ across life history stages. The stress-induced elevation of plasma CORT was consistently associated with decreased plasma UA, suggesting a role for CORT in the regulation of plasma UA during stress. During stress plasma GLU either increased (pre-breeding), did not change (breeding), or decreased (molt and non-breeding), and plasma T either decreased (pre-breeding and breeding) or did not change (molt and non-breeding). These data provide only partial support to the hypothesis that CORT secretion during acute stress exerts a hyperglycemic action or is responsible for the observed decrease in plasma T taking place at certain life history stages. They also do not support the hypothesis that rapid changes in plasma T influence glycemia. PMID:27292791

  8. Effect of housefly maggot meal (magmeal) diets on the performance, concentration of plasma glucose, cortisol and blood characteristics of Oreochromis niloticus fingerlings.

    PubMed

    Ogunji, J O; Kloas, W; Wirth, M; Neumann, N; Pietsch, C

    2008-08-01

    A 56-day feeding trial was conducted to access the effect of housefly maggot meal (magmeal) diets on the performance, concentration of plasma glucose, cortisol and blood characteristics of Oreochromis niloticus fingerlings. Seven feeds formulated to contain 36% protein and 20 kJ g(-1) gross energy (dry matter basis), were prepared by replacing fish meal with magmeal. Fifteen fingerlings (initial average weight 2.0 +/- 0.1 g) stocked per experimental tank were fed in triplicates at 5% body weight in two portions per day (a level previously established). Growth and food conversion ratio were adequate and comparable without any significant differences (p < 0.5) between feeding groups. Mean values for haematocrit and plasma glucose were not significantly different (p < 0.05) among the feeding groups. Fish group fed control diet (containing highest inclusion level of fish meal and without magmeal) gave the lowest haemoglobin concentration (5.96 +/- 0.22 g dl(-1)). This value was significantly different from other feeding groups. Stressful conditions in fish and in mammals are associated with decreased growth, haematocrit (packed cell volume) and haemoglobin values, increased whole blood glucose (hyperglycaemia) and plasma cortisol concentrations. No such physiological changes were observed in this study. Results suggest that feeding O. niloticus fingerling with magmeal diets did not cause any form of physiological stress. Magmeal can be used as a good alternative protein source in tilapia diets. PMID:18662361

  9. Effect of an aqueous extract of Scoparia dulcis on blood glucose, plasma insulin and some polyol pathway enzymes in experimental rat diabetes.

    PubMed

    Latha, M; Pari, L

    2004-04-01

    The effects of an aqueous extract of the plant Scoparia dulcis (200 mg/kg) on the polyol pathway and lipid peroxidation were examined in the liver of streptozotocin adult diabetic male albino Wistar rats. The diabetic control rats (N = 6) presented a significant increase in blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides, and a significant decrease in plasma insulin and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) compared to normal rats (N = 6). Scoparia dulcis plant extract (SPEt, 200 mg kg-1 day-1) and glibenclamide (600 microg kg-1 day-1), a reference drug, were administered by gavage for 6 weeks to diabetic rats (N = 6 for each group) and significantly reduced blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin, TBARS, and hydroperoxides, and significantly increased plasma insulin, GPx, GST and GSH activities in liver. The effect of the SPEt was compared with that of glibenclamide. The effect of the extract may have been due to the decreased influx of glucose into the polyol pathway leading to increased activities of antioxidant enzymes and plasma insulin and decreased activity of sorbitol dehydrogenase. These results indicate that the SPEt was effective in attenuating hyperglycemia in rats and their susceptibility to oxygen free radicals. PMID:15064821

  10. Determinants of Fasting Plasma Glucose and Glycosylated Hemoglobin Among Low Income Latinos with Poorly Controlled Type 2 Diabetes

    PubMed Central

    Kollannoor-Samuel, Grace; Chhabra, Jyoti; Fernandez, Maria Luz; Vega-LÓpez, Sonia; Pérez, Sofia Segura; Damio, Grace; Calle, Mariana C.; D’Agostino, Darrin; Pérez-Escamilla, Rafael

    2011-01-01

    The objective of this study was to identify demographic, socio-economic, acculturation, lifestyle, sleeping pattern, and biomedical determinants of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), among Latinos with type 2 diabetes (T2D). Latino adults (N = 211) with T2D enrolled in the DIALBEST trial were interviewed in their homes. Fasting blood samples were also collected in the participants’ homes. Because all participants had poor glucose control, above-median values for FPG (173 mg/dl) and HbA1c (9.2%) were considered to be indicative of poorer glycemic control. Multivariate analyses showed that receiving heating assistance (OR: 2.20; 95% CI: 0.96–4.96), and having a radio (3.11, 1.16–8.35), were risk factors for higher FPG levels, and lower income (10.4, 1.54–69.30) was a risk factor for higher HbA1c levels. Lower carbohydrate intake during the previous day (0.04; 0.005–0.37), as well as regular physical activity (0.30; 0.13–0.69), breakfast (2.78; 1.10–6.99) and dinner skipping (3.9; 1.03–14.9) during previous week were significantly associated with FPG concentrations. Being middle aged (2.24, 1.12–4.47), 30–60 min of sleep during the day time (0.07, 0.01–0.74) and having medical insurance (0.31, 0.10–0.96) were predictors of HbA1c. Results suggest that contemporaneous lifestyle behaviors were associated with FPG and contextual biomedical factors such as health care access with HbA1c. Lower socio-economic status indicators were associated with poorer FPG and HbA1c glycemic control. PMID:21181446

  11. Multiple Functional Polymorphisms in the G6PC2 Gene Contribute to the Association with Higher Fasting Plasma Glucose Levels

    PubMed Central

    Baerenwald, D. A.; Bonnefond, A.; Bouatia-Naji, N.; Flemming, B. P.; Umunakwe, O. C.; Oeser, J. K.; Pound, L. D.; Conley, N. L.; Cauchi, S.; Lobbens, S.; Eury, E.; Balkau, B.; Lantieri, O.; Dadi, P. K.; Jacobson, D. A.; Froguel, P.; O’Brien, R. M.

    2014-01-01

    Aims We previously identified the G6PC2 locus as a strong determinant of fasting plasma glucose (FPG) and showed that a common G6PC2 intronic single nucleotide polymorphism (SNP) (rs560887) and two common G6PC2 promoter SNPs (rs573225 and rs13431652) are highly associated with FPG. However, these promoter SNPs have complex effects on G6PC2 fusion gene expression, and our data suggested that only rs13431652 is a potentially causative SNP. Here we examine the effect of rs560887 on G6PC2 pre-mRNA splicing and the contribution of an additional common G6PC2 promoter SNP, rs2232316, to the association signal. Methods Mini-gene analyzes characterized the effect of rs560887 on G6PC2 pre-mRNA splicing. Fusion gene and gel retardation analyses characterized the effect of rs2232316 on G6PC2 promoter activity and transcription factor binding. The genetic association of rs2232316 with FPG variation was assessed using regression adjusted for age, gender and body mass index in 4,220 Europeans with normal FPG. Results & Conclusions The rs560887-G allele was shown to enhance G6PC2 pre-mRNA splicing while the rs2232316-A allele enhanced G6PC2 transcription by promoting Foxa2 binding. Genetic analyses provide evidence for association of the rs2232316-A allele with increased FPG (β=0.04 mmol/l; P=4.3×10−3) as part of the same signal as rs560887, rs573225 and rs13431652. As with rs13431652 the in situ functional data with rs560887 and rs2232316 are in accord with the putative function of G6PC2 in pancreatic islets and suggest that all three are potentially causative SNPs that contribute to the association between G6PC2 and FPG. PMID:23508304

  12. Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations

    PubMed Central

    Orho-Melander, Marju; Melander, Olle; Guiducci, Candace; Perez-Martinez, Pablo; Corella, Dolores; Roos, Charlotta; Tewhey, Ryan; Rieder, Mark J.; Hall, Jennifer; Abecasis, Goncalo; Tai, E. Shyong; Welch, Cullan; Arnett, Donna K.; Lyssenko, Valeriya; Lindholm, Eero; Saxena, Richa; de Bakker, Paul I.W.; Burtt, Noel; Voight, Benjamin F.; Hirschhorn, Joel N.; Tucker, Katherine L.; Hedner, Thomas; Tuomi, Tiinamaija; Isomaa, Bo; Eriksson, Karl-Fredrik; Taskinen, Marja-Riitta; Wahlstrand, Björn; Hughes, Thomas E.; Parnell, Laurence D.; Lai, Chao-Qiang; Berglund, Göran; Peltonen, Leena; Vartiainen, Erkki; Jousilahti, Pekka; Havulinna, Aki S.; Salomaa, Veikko; Nilsson, Peter; Groop, Leif; Altshuler, David; Ordovas, Jose M.; Kathiresan, Sekar

    2008-01-01

    OBJECTIVE—Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry and to fine- map across the associated genomic interval. RESEARCH DESIGN AND METHODS—We performed association studies in 12 independent cohorts comprising >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the ∼417-kb region of linkage disequilibrium spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval. RESULTS—We provide comprehensive evidence that GCKR rs780094 is associated with opposite effects on fasting plasma triglyceride (Pmeta = 3 × 10−56) and glucose (Pmeta = 1 × 10−13) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P = 5 × 10−5). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r2 = 0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS—These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. PMID:18678614

  13. Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with Type 1 diabetes.

    PubMed

    Marcovecchio, M Loredana; Widmer, Barry; Dunger, David B; Dalton, R Neil

    2008-12-01

    ADMA (asymmetric dimethylarginine), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations in plasma glucose and insulin on plasma ADMA levels in young people with T1D (Type 1 diabetes). Fifteen young patients (ten males) with T1D, median age 18.3 (13.2-24.4) years, HbA(1c) (glycated haemoglobin) 9% (6.4-13.6%), underwent an overnight (18:00-08:00 hours) variable insulin infusion for euglycaemia, followed by a hyperinsulinaemic-euglycaemic clamp (08:00-12:00 hours). Blood samples were collected every 15 min for determination of ADMA, SDMA (symmetric dimethylarginine), valine, phenylalanine, arginine, creatinine and glucose. Insulin levels were assessed every 30 min. During the overnight period, glucose levels increased following the evening meal. In response to the protein intake there was a significant increase in ADMA, arginine, valine, phenylalanine and creatinine. For the remaining part of the night, glucose levels progressively decreased reaching 5 mmol/l by 04:00 hours. ADMA and SDMA did not change significantly. During the hyperinsulinaemic clamp, a significant fall in ADMA was observed, from 0.468+/-0.056 to 0.364+/-0.050 micromol/l (P<0.001). A significant fall was also found in SDMA, valine, phenylalanine, arginine and the ADMA/SDMA ratio (all P<0.001), but not in creatinine levels. No correlation was found between insulin sensitivity and ADMA. We conclude that acute changes in glycaemia do not significantly affect plasma ADMA levels whereas infusion of insulin significantly reduces ADMA, suggesting an important role for insulin in the regulation of this cardiovascular risk factor. PMID:18498242

  14. Quantification of [1-(5-fluoropentyl)-1H-indol-3-yl](naphthalene-1-yl)methanone (AM-2201) and 13 metabolites in human and rat plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Carlier, Jeremy; Scheidweiler, Karl B; Wohlfarth, Ariane; Salmeron, Bonita D; Baumann, Michael H; Huestis, Marilyn A

    2016-06-17

    AM-2201 is a popular synthetic cannabinoid first synthesized in 2000. AM-2201 pharmacokinetic and pharmacodynamic data are scarce, requiring further investigation. We developed a sensitive method for quantifying AM-2201 and 13 metabolites in plasma to provide a tool to further metabolic, pharmacokinetic and pharmacodynamic studies. Analysis was performed by liquid chromatography-tandem mass spectrometry. Chromatographic separation was performed by gradient elution on a biphenyl column with 0.1% formic acid in water/0.1% formic acid in acetonitrile:methanol 50:50 (v/v) mobile phase. Sample preparation (75μL) consisted of an enzymatic hydrolysis and a supported liquid extraction. The method was validated with human plasma with a 0.025 or 0.050-50μg/L working range, and cross-validated for rat plasma. Analytical recovery was 88.8-110.1% of target concentration, and intra- (n=30) and inter-day (n=30) imprecision<11.9% coefficient of variation. Method recoveries and matrix effects ranged from 58.4-84.4% and -62.1 to -15.6%, respectively. AM-2201 and metabolites were stable (±20%) at room temperature for 24h, at 4°C for 72h, and after three freeze-thaw cycles, and for 72h in the autosampler after extraction. The method was developed for pharmacodynamic and pharmacokinetic studies with controlled administration in rats but is applicable for pre-clinical and clinical research and forensic investigations. Rat plasma specimen analysis following subcutaneous AM-2201 administration demonstrated the suitability of the method. AM-2201, JWH-018 N-(5-hydroxypentyl), and JWH-018 N-pentanoic acid concentrations were 4.8±1.0, 0.15±0.03, and 0.34±0.07μg/L, respectively, 8h after AM-2201 administration at 0.3mg/kg (n=5). PMID:27208987

  15. β-3AR W64R Polymorphism and 30-Minute Post-Challenge Plasma Glucose Levels in Obese Children

    PubMed Central

    Verdi, Hasibe; Tulgar Kınık, Sibel; Yılmaz Yalçın, Yaprak; Muratoğlu Şahin, Nursel; Yazıcı, Ayşe Canan; Ataç, F. Belgin

    2015-01-01

    Objective: In this study, we aimed to investigate the association of W64R polymorphism of the β3-adrenergic receptor gene (β-3AR) with childhood obesity and related pathologies. Methods: β-3AR gene W64R genotyping was carried out in 251 children aged 6-18 years. Of these subjects, 130 were obese (62 boys) and 121 were normal-weight (53 boys). In the obese group, fasting lipids, glucose and insulin levels were measured. Oral glucose tolerance test (OGTT) was performed in 75 of the obese patients. Results: The frequency of W64R genotype was similar in obese and non-obese children. In obese children, relative body mass index, waist-to-hip ratio, serum lipid, glucose and insulin levels, as well as homeostasis model assessment of insulin resistance (HOMA-IR) scores were not different between Arg allele carriers (W64R and R64R) and noncarriers (W64W). In 75 obese children, OGTT results showed that Arg allele carriers had significantly higher 30-minute glucose levels (p=0.027). Conclusion: W64R polymorphism of the β-3AR gene is not associated with obesity and waist-to-hip ratio in Turkish children. Although there were no relationships between the genotypes and lipid, glucose/insulin levels or HOMA-IR, the presence of W64R variant seemed to have an unfavorable influence on early glucose excursion after glucose loading. PMID:25800470

  16. Effect of aspartame and protein, administered in phenylalanine-equivalent doses, on plasma neutral amino acids, aspartate, insulin and glucose in man.

    PubMed

    Møller, S E

    1991-05-01

    Six human males each received 0.56 g phenylalanine (Phe) in the form of 1.0 g aspartame or 12.2 g bovine albumin in 200 ml water or water alone. Venous blood samples collected before consumption and during the following 4 hr were assayed for plasma levels of large, neutral amino acids (LNAA), aspartate, insulin and glucose. The area under the curve for plasma Phe was 40% greater, although not significant, after aspartame compared with albumin intake. The indicated increased clearance rate of plasma Phe after albumin may be caused by the significant increase of insulin, on which aspartame had no effect. There was a significant main effect of aspartame for plasma tyrosine but not for tryptophan, valine, isoleucine or leucine. Plasma aspartate was significantly increased at 0.25 hr after the aspartame intake. The percentage Phe/LNAA decreased slightly in response to albumin but increased 55% after aspartame and remained significantly increased for 2 hr. Tyrosine/LNAA increased and tryptophan/LNAA decreased modestly after aspartame intake. The study showed that the intake of aspartame in a not unrealistically high dose produced a marked and persistent increase of the availability of Phe to the brain, which was not observed after protein intake. The study indicated, furthermore, that Phe was cleared faster from the plasma after consumption of protein compared with aspartame. PMID:1946186

  17. Non-thermal plasma with 2-deoxy-D-glucose synergistically induces cell death by targeting glycolysis in blood cancer cells

    NASA Astrophysics Data System (ADS)

    Kaushik, Neha; Lee, Su Jae; Choi, Tae Gyu; Baik, Ku Youn; Uhm, Han Sup; Kim, Chung Hyeok; Kaushik, Nagendra Kumar; Choi, Eun Ha

    2015-03-01

    In this study, we show the selective and efficient anti-cancer effects of plasma (at a low dose) when cell metabolic modifiers are also included. 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor, was used with effective doses of non-thermal plasma, synergistically attenuating cell metabolic viability and inducing caspase-dependent and independent cell death. The combination treatment decreased the intracellular ATP and lactate production in various types of blood cancer cells in vitro. Taken together, our findings suggest that 2-DG enhances the efficacy and selectivity of plasma and induces the synergistic inhibition of cancer cell growth by targeting glycolysis and apoptosis. Specifically, this treatment strategy demonstrated an enhanced growth inhibitory effect of plasma in the presence of a metabolic modifier that was selective against cancer cells, not non-malignant cells. This is the first study to report the advantage of combining plasma with 2-DG to eradicate blood cancer cells. Finally, we conclude that 2-DG with non-thermal plasma may be used as a combination treatment against blood cancer cells.

  18. Mosapride, a selective serotonin 5-HT4 receptor agonist, and alogliptin, a selective dipeptidyl peptidase-4 inhibitor, exert synergic effects on plasma active GLP-1 levels and glucose tolerance in mice.

    PubMed

    Nonogaki, Katsunori; Kaji, Takao

    2015-12-01

    Pharmacologic stimulation of serotonin 5-HT4 receptors increased plasma active glucagon-like-peptide-1 (GLP-1) levels independent of feeding, and that pharmacologic stimulation of 5-HT4 receptors and pharmacologic inhibition of dipeptidyl peptidase-4 exerted synergic effects on plasma active GLP-1 levels and glucose tolerance in mice. PMID:26497774

  19. First autoclave-sterilized platelet-additive solution containing glucose with a physiological pH for the preparation of plasma-poor platelet concentrates.

    PubMed

    Shimizu, T; Shibata, K; Kora, S

    1992-01-01

    The glucose-free platelet-additive solution (termed AR solution), developed by Adams and Rock [Transfusion 1988;28:217-220], was modified by adding glucose as an energy substrate for platelets and maltose to prevent platelet lysis and by replacing sodium gluconate with sodium phosphate for better pH maintenance. The new platelet-additive solution (termed Seto solution) contained 90 mM NaCl, 5 mM KCl, 3 mM MgCl2, 17 mM tri-sodium citrate, 4.9 mM NaH2PO4, 20.1 mM Na2HPO4, 23 mM sodium acetate, 28.8 mM maltose, and 23.5 mM glucose with a pH of 7.4. The solution was sterilized by autoclaving in plastic bags in nitrogen to prevent glucose caramelization at high pH. Plasma-poor platelet concentrates prepared by adding Seto solution to the pelleted platelet buttons were stored in a LE-2 polyolefin bag at 22 degrees C with constant agitation for 5 days. The platelets suspended in Seto solution maintained oxygen consumption at a rate of 1.1 nmol/min/10(9) platelets after 5-day storage, with glucose consumption and lactate production rates of 0.5 +/- 0.2 and 1.2 +/- 0.2 nmol/min/10(9) platelets, respectively. This resulted in a final mean pH of 7.0. Those suspended in AR solution ceased glycolysis within 3 days because residual plasma glucose had been consumed. This was associated with decreases in percent hypotonic shock response and aggregation induced by adenosine diphosphate and collagen. Lactate dehydrogenase discharge in AR solution was 5 and 8 times higher at day 3 and day 5, respectively, than that of Seto solution. Morphologically, there were no ballooned platelets after storage in Seto solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1519373

  20. Fasting Plasma Glucose as Initial Screening for Diabetes and Prediabetes in Irish Adults: The Diabetes Mellitus and Vascular Health Initiative (DMVhi)

    PubMed Central

    Sinnott, Margaret; Kinsley, Brendan T.; Jackson, Abaigeal D.; Walsh, Cathal; O’Grady, Tony; Nolan, John J.; Gaffney, Peter; Boran, Gerard; Kelleher, Cecily; Carr, Bernadette

    2015-01-01

    Objective Type 2 diabetes has a long pre clinical asymptomatic phase. Early detection may delay or arrest disease progression. The Diabetes Mellitus and Vascular health initiative (DMVhi) was initiated as a prospective longitudinal cohort study on the prevalence of undiagnosed Type 2 diabetes and prediabetes, diabetes risk and cardiovascular risk in a cohort of Irish adults aged 45-75 years. Research Design and Methods Members of the largest Irish private health insurance provider aged 45 to 75 years were invited to participate in the study. Exclusion criteria: already diagnosed with diabetes or taking oral hypoglycaemic agents. Participants completed a detailed medical questionnaire, had weight, height, waist and hip circumference and blood pressure measured. Fasting blood samples were taken for fasting plasma glucose (FPG). Those with FPG in the impaired fasting glucose (IFG) range had a 75gm oral glucose tolerance test performed. Results 122,531 subjects were invited to participate. 29,144 (24%) completed the study. The prevalence of undiagnosed diabetes was 1.8%, of impaired fasting glucose (IFG) was 7.1% and of impaired glucose tolerance (IGT) was 2.9%. Dysglycaemia increased among those aged 45-54, 55-64 and 65-75 years in both males (10.6%, 18.5%, 21.7% respectively) and females (4.3%, 8.6%, 10.9% respectively). Undiagnosed T2D, IFG and IGT were all associated with gender, age, blood pressure, BMI, abdominal obesity, family history of diabetes and triglyceride levels. Using FPG as initial screening may underestimate the prevalence of T2D in the study population. Conclusions This study is the largest screening study for diabetes and prediabetes in the Irish population. Follow up of this cohort will provide data on progression to diabetes and on cardiovascular outcomes. PMID:25874867

  1. Association between the rs4753426 polymorphism in MTNR1B with fasting plasma glucose level and pancreatic β-cell function in gestational diabetes mellitus.

    PubMed

    Zhan, Y; Li, C; Gao, Q; Chen, J; Yu, S; Liu, S G

    2015-01-01

    We investigated the association between rs4753426 single nucleotide polymorphisms in the melatonin receptor 1B (MTNR1B) gene and the risk of developing gestational diabetes mellitus (GDM). A total of 516 gravidas (186 with GDM and 330 non-diabetic controls) were enrolled in the study. Genotype and allele frequencies of rs4753426 in the MTNR1B gene were detected by DNA sequencing. Fasting plasma glucose and fasting insulin levels were measured to calculate the homeostasis model assessment for insulin resistance (HOMA-IR) and for β-cell function. Three genotypes (CC, CT, and TT) were found in both groups. The frequencies of CC, CT, and TT genotypes for the GDM group were 70.97, 22.58, and 6.45% vs 53.03, 39.70, and 7.27% in the control group, respectively. Significant differences were observed in genotype frequencies between groups (P < 0.05). T and C allele frequencies in the GDM group were 17.74 and 82.26%, respectively, and in the control group were 27.12 and 72.88%, respectively. Significant differences in T and C allele frequencies were found between groups (P < 0.05). In the GDM group, the C allele was associated with increased fasting plasma glucose level and reduced pancreatic β-cell function (P < 0.05). There were no significant differences in total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein concentration, or HOMA-IR between groups (P > 0.05). The single nucleotide polymorphism rs4753426 in MTNR1B may be a susceptibility gene locus for GDM, and the C allele may contribute to the increased fasting plasma glucose level and reduced pancreatic β-cell function. PMID:26345809

  2. One-hour versus two-hour postprandial blood glucose measurement in women with gestational diabetes mellitus: which is more predictive?

    PubMed

    Ozgu-Erdinc, A Seval; Iskender, Cantekin; Uygur, Dilek; Oksuzoglu, Aysegul; Seckin, K Doga; Yeral, M Ilkin; Kalaylioglu, Zeynep I; Yucel, Aykan; Danisman, A Nuri

    2016-06-01

    The purpose of this study is to investigate postprandial 1-h (PP1) and 2-h (PP2) blood glucose measurements' correlation with adverse perinatal outcomes. This prospective cohort study consisted of 259 women with gestational diabetes mellitus. During each antenatal visit, HbA1c and fasting plasma glucose (FPG) as well as plasma glucose at PP1 and PP2 were analyzed. There were 144 patients on insulin therapy and 115 patients on diet therapy. A total of 531 blood glucose measurements were obtained at different gestational ages between 24 and 41 gestational weeks. PP2 plasma glucose measurements (but not PP1) were positively correlated with fetal macrosomia. But on adjusted analysis, neither PP1 nor PP2 measurements predicted perinatal complications. In addition to PP1 and PP2, neither FPG nor HbA1c were able to predict perinatal complications or fetal macrosomia when controlled for confounding factors except for a positive correlation between fetal macrosomia and HbA1c in patients on diet therapy. Postprandial 1-h and postprandial 2-h plasma glucose measurements were not superior to each other in predicting fetal macrosomia or perinatal complications. Based on our findings, it can be concluded that both methods may be suitable for follow-up as there are no clear advantages of one measurement over the other. PMID:26645814

  3. Anger, and plasma lipid, lipoprotein, and glucose levels in healthy women: the mediating role of physical fitness.

    PubMed

    Siegman, Aron Wolfe; Malkin, Amy R; Boyle, Stephen; Vaitkus, Mark; Barko, William; Franco, Edward

    2002-02-01

    The association between anger, lipid profiles, and glucose levels were examined in this study of 103 middle aged, healthy women. A principal component factor analysis of Spielberger's Trait Anger and Anger Expression scales yielded two anger factors: Impulsive Anger-Out and Neurotic Anger. Impulsive anger-out significantly predicted a negative lipid profile (high total serum cholesterol (TSC), low density lipoproteins (LDL), TSC/HDL (high density lipids), and triglyceride levels) and heightened glucose levels, but only in physically unfit women. Neurotic anger did not predict lipid and glucose levels. These findings parallel previous findings regarding the two anger dimensions and CHD, with only impulsive anger-out predicting CHD. Furthermore, our findings indicate that the protective effect of physical fitness, previously documented for men, also occurs in women. PMID:11845555

  4. Effect of pertussis toxin pretreated centrally on blood glucose level induced by stress.

    PubMed

    Suh, Hong-Won; Sim, Yun-Beom; Park, Soo-Hyun; Sharma, Naveen; Im, Hyun-Ju; Hong, Jae-Seung

    2016-09-01

    In the present study, we examined the effect of pertussis toxin (PTX) administered centrally in a variety of stress-induced blood glucose level. Mice were exposed to stress after the pretreatment of PTX (0.05 or 0.1 µg) i.c.v. or i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min after stress stimulation. The blood glucose level was increased in all stress groups. The blood glucose level reached at maximum level after 30 min of stress stimulation and returned to a normal level after 2 h of stress stimulation in restraint stress, physical, and emotional stress groups. The blood glucose level induced by cold-water swimming stress was gradually increased up to 1 h and returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX, a Gi inhibitor, alone produced a hypoglycemia and almost abolished the elevation of the blood level induced by stress stimulation. The central pretreatment with PTX caused a reduction of plasma insulin level, whereas plasma corticosterone level was further up-regulated in all stress models. Our results suggest that the hyperglycemia produced by physical stress, emotional stress, restraint stress, and the cold-water swimming stress appear to be mediated by activation of centrally located PTX-sensitive G proteins. The reduction of blood glucose level by PTX appears to due to the reduction of plasma insulin level. The reduction of blood glucose level by PTX was accompanied by the reduction of plasma insulin level. Plasma corticosterone level up-regulation by PTX in stress models may be due to a blood glucose homeostatic mechanism. PMID:27610033

  5. Effect of pertussis toxin pretreated centrally on blood glucose level induced by stress

    PubMed Central

    Suh, Hong-Won; Sim, Yun-Beom; Park, Soo-Hyun; Sharma, Naveen; Im, Hyun-Ju

    2016-01-01

    In the present study, we examined the effect of pertussis toxin (PTX) administered centrally in a variety of stress-induced blood glucose level. Mice were exposed to stress after the pretreatment of PTX (0.05 or 0.1 µg) i.c.v. or i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min after stress stimulation. The blood glucose level was increased in all stress groups. The blood glucose level reached at maximum level after 30 min of stress stimulation and returned to a normal level after 2 h of stress stimulation in restraint stress, physical, and emotional stress groups. The blood glucose level induced by cold-water swimming stress was gradually increased up to 1 h and returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX, a Gi inhibitor, alone produced a hypoglycemia and almost abolished the elevation of the blood level induced by stress stimulation. The central pretreatment with PTX caused a reduction of plasma insulin level, whereas plasma corticosterone level was further up-regulated in all stress models. Our results suggest that the hyperglycemia produced by physical stress, emotional stress, restraint stress, and the cold-water swimming stress appear to be mediated by activation of centrally located PTX-sensitive G proteins. The reduction of blood glucose level by PTX appears to due to the reduction of plasma insulin level. The reduction of blood glucose level by PTX was accompanied by the reduction of plasma insulin level. Plasma corticosterone level up-regulation by PTX in stress models may be due to a blood glucose homeostatic mechanism. PMID:27610033

  6. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

    NASA Astrophysics Data System (ADS)

    Gjedde, Albert; Crone, Christian

    1981-10-01

    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

  7. Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients

    PubMed Central

    Kraus, William E.; Blach, Colette; Haynes, Carol S.; Dowdy, Elaine; Miranda, Marie Lynn; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Mukerjee, Shaibal; Stallings, Casson; Smith, Luther A.; Gregory, Simon G.; Shah, Svati H.; Hauser, Elizabeth R.; Neas, Lucas M.

    2015-01-01

    Background The relationship between traffic-related air pollution (TRAP) and risk factors for cardiovascular disease needs to be better understood in order to address the adverse impact of air pollution on human health. Objective We examined associations between roadway proximity and traffic exposure zones, as markers of TRAP exposure, and metabolic biomarkers for cardiovascular disease risk in a cohort of patients undergoing cardiac catheterization. Methods We performed a cross-sectional study of 2,124 individuals residing in North Carolina (USA). Roadway proximity was assessed via distance to primary and secondary roadways, and we used residence in traffic exposure zones (TEZs) as a proxy for TRAP. Two categories of metabolic outcomes were studied: measures associated with glucose control, and measures associated with lipid metabolism. Statistical models were adjusted for race, sex, smoking, body mass index, and socioeconomic status (SES). Results An interquartile-range (990 m) decrease in distance to roadways was associated with higher fasting plasma glucose (β = 2.17 mg/dL; 95% CI: –0.24, 4.59), and the association appeared to be limited to women (β = 5.16 mg/dL; 95% CI: 1.48, 8.84 compared with β = 0.14 mg/dL; 95% CI: –3.04, 3.33 in men). Residence in TEZ 5 (high-speed traffic) and TEZ 6 (stop-and-go traffic), the two traffic zones assumed to have the highest levels of TRAP, was positively associated with high-density lipoprotein cholesterol (HDL-C; β = 8.36; 95% CI: –0.15, 16.9 and β = 5.98; 95% CI: –3.96, 15.9, for TEZ 5 and 6, respectively). Conclusion Proxy measures of TRAP exposure were associated with intermediate metabolic traits associated with cardiovascular disease, including fasting plasma glucose and possibly HDL-C. Citation Ward-Caviness CK, Kraus WE, Blach C, Haynes CS, Dowdy E, Miranda ML, Devlin RB, Diaz-Sanchez D, Cascio WE, Mukerjee S, Stallings C, Smith LA, Gregory SG, Shah SH, Hauser ER, Neas LM. 2015. Association of roadway

  8. Influence of excessive dietary protein intake during late gestation on drylot beef cow performance and progeny growth, carcass characteristics, and plasma glucose and insulin concentrations.

    PubMed

    Wilson, T B; Long, N M; Faulkner, D B; Shike, D W

    2016-05-01

    Spring-calving cows ( = 49) were used to investigate the effects of excessive prepartum dietary protein intake on late gestation cow performance as well as subsequent progeny growth, carcass characteristics, and plasma glucose and insulin concentrations. Treatments were formulated to be isocaloric and provide 100% (REQ) or 129% (HP) of CP requirement. Treatments were limit-fed 78 ± 12 d prepartum to calving. All cows were fed a common diet postpartum. Cow BW and BCS were recorded at initiation of treatments and within 48 h post-calving. Milk production was estimated via the weigh-suckle-weigh technique 69 ± 11 d postpartum. Calf BW was measured at birth and at weaning (121 ± 11 d of age). Progeny ( = 42) were weaned as a group and placed into a feedlot and fed a common finishing diet. Glucose and insulin concentrations were analyzed on a subset of progeny (12 per treatment) 90, 120, 150, 180, 210, and 240 min post-feeding, 2 d before slaughter (342 ± 11 d of age). Treatment had no effect ( ≥ 0.22) on cow BW, BCS, milk production, and subsequent reproduction or progeny preweaning growth. Progeny finishing growth and marbling scores were not affected ( ≥ 0.24) by treatment, yet 12th rib fat thickness ( < 0.01), KPH ( = 0.04), and YG ( = 0.01) were greater for progeny born to HP dams. Progeny born to HP dams had decreased ( ≤ 0.01) glucose and insulin concentrations, and insulin to glucose ratios, indicating greater insulin sensitivity. Although feeding cows 129% of CP requirement during late gestation did not affect cow performance or progeny preweaning or finishing period growth; carcass adiposity was increased by maternal treatment. PMID:27285701

  9. Preparation of penta-O-galloyl-β-D-glucose from tannic acid and plasma pharmacokinetic analyses by liquid-liquid extraction and reverse-phase HPLC.

    PubMed

    Li, Li; Shaik, Ahmad Ali; Zhang, Jinhui; Nhkata, Katai; Wang, Lei; Zhang, Yong; Xing, Chengguo; Kim, Sung-Hoon; Lü, Junxuan

    2011-02-20

    The gallotannin penta-O-galloyl-beta-D-glucose (PGG) has many biological activities including in vivo anti-cancer efficacy. We present in this paper a scaled-up protocol for its preparation in high purity from tannic acid by acidic methanolysis with typical yield of 15%. We also describe a method for the analysis of PGG in mouse plasma by HPLC and its application in preliminary pharmacokinetic studies. A liquid-liquid extraction (LLE) protocol was optimized for the extraction of PGG from mouse plasma. The extraction efficiency for PGG at 1 μg/mL in mouse plasma was 70.0±1.3% (n=5). The limit of detection (LOD) for PGG was approximately 0.2 μg/mL. Preliminary pharmacokinetic parameters of PGG following a single i.p. injection with 5% ethanol/saline vehicle in mice were established. The peak plasma PGG concentrations (C(max)) were approximately 3-4 μM at a dose of 0.5 mg per mouse (∼20 mg/kg) at 2 h post-injection (T(max)). PMID:20970943

  10. Dynamic stereochemistry of erigeroside by measurement of 1H- 1H and 13C- 1H coupling constants

    NASA Astrophysics Data System (ADS)

    Tafazzoli, Mohsen; Ghiasi, Mina; Moridi, Mahdi

    2008-07-01

    Erigeroside was extracted from Satureja khuzistanica Jamzad (Marzeh Khuzistani in Persian, family of lamiaceae), and 1H, 13C, 13C{ 1H}, 1H- 1H COSY, HMQC and J-HMBC were obtained to identify this compound and determine a complete set of J-coupling constants ( 1JC-H, 2JC-H, 3JC-H and 3JH-H) values within the exocyclic hydroxymethyl group (CH 2OH) and anomeric center. In parallel, density functional theory (DFT) using B3LYP functional and split-valance 6-311++G** basis set has been used to optimized the structures and conformers of erigeroside. In all calculations solvent effects were considered using a polarized continuum (overlapping spheres) model (PCM). The dependencies of 1J, 2J and 3J involving 1H and 13C on the C 5'-C 6' ( ω), C 6'-O 6' ( θ) and C 1'-O 1' ( φ) torsion angles in erigeroside were computed using DFT method. Complete hyper surfaces for 1JC1',H1', 2JC5',H6'R, 2JC5',H6'S, 2JC6',H5', 3JC4',H6'R, 3JC4',H6'S and 2JH6'R-H5'S as well as 3JH5',H6'R were obtained and used to derive Karplus equations to correlate these couplings to ω, θ and φ. These calculated J-couplings are in agreement with experimental values. These results confirm the reliability of DFT calculated coupling constants in aqueous solution.

  11. Syntheses of vanadyl and zinc(II) complexes of 1-hydroxy-4,5,6-substituted 2(1H)-pyrimidinones and their insulin-mimetic activities.

    PubMed

    Yamaguchi, Mika; Wakasugi, Kei; Saito, Ryota; Adachi, Yusuke; Yoshikawa, Yutaka; Sakurai, Hiromu; Katoh, Akira

    2006-02-01

    Control of the glucose level in the blood plasma has been achieved in vitro and in vivo by administration of vanadium and zinc in form of inorganic salts. It has been shown that elements are poorly absorbed in their inorganic forms and required high doses which have been associated with undesirable side effects. Many researchers, therefore, have focused on metal complexes that were prepared from VOSO(4) or ZnSO(4) and low-molecular-weight bidentate ligands. Seven kinds of 1-hydroxy-4,6-disubstituted and 1-hydroxy-4,5,6-trisubstituted-2(1H)-pyrimidinones were synthesized by reaction of N-benzyloxyurea and beta-diketones and subsequent removal of the protecting group. Six kinds of 1-hydroxy-4-(substituted)amino-2(1H)-pyrimidinones were synthesized by the substitution reaction of 1-benzyloxy-4-(1',2',4'-triazol-1'-yl)-2(1H)-pyrimidinone with various alkyl amines or amino acids. Treatment with VOSO(4) and ZnSO(4) or Zn(OAc)(2) afforded vanadyl(IV) and zinc(II) complexes which were characterized by means of (1)H NMR, IR, EPR, and UV-vis spectroscopies, and combustion analysis. The in vitro insulin-mimetic activity of these complexes was evaluated from 50% inhibitory concentrations (IC(50)) on free fatty acid (FFA) release from isolated rat adipocytes treated with epinephrine. Vanadyl complexes of 4,6-disubstituted-2(1H)-pyrimidinones showed higher insulin-mimetic activities than those of 4,5,6-trisubstituted ones. On the other hand, Zn(II) complexes showed lower insulin-mimetic activities than VOSO(4) and ZnSO(4) as positive controls. It was found that the balance of the hydrophilicity and/or hydrophobicity is important for higher insulin-mimetic activity. The in vivo insulin-mimetic activity was evaluated with streptozotocin (STZ)-induced diabetic rats. Blood glucose levels were lowered from hyperglycemic to normal levels after the treatment with bis(1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato)oxovanadium(IV) by daily intraperitoneal injections. The improvement in

  12. Comparison of measurements of canine plasma creatinine, glucose, proteins, urea, alanine aminotransferase, and alkaline phosphatase obtained with Spotchem SP 4430 and Vitros 250 analyzers.

    PubMed

    Trumel, C; Diquélou, A; Germain, C; Palanché, F; Braun, J P

    2005-12-01

    The suitability of the Spotchem 4430 benchtop biochemistry analyzer for canine blood samples was tested for creatinine, glucose, proteins, urea, alkaline phosphatases and alanine aminotransferase. Results obtained from whole blood and corresponding heparin plasma were identical except for proteins which were higher in plasma (n=10). Between series imprecision (n=10) was <5% for substrates and <10% for enzymes. Comparison of results from 100 Li-heparin samples with those measured with a Vitros 250 analyzer showed good correlation (r>0.93). The slopes of the Passing-Bablock's regression ranged from 0.90 to 1.20 and intercepts were low. The mean biases were low, except for creatinine for which the results obtained by Spotchem (Jaffe reaction) were about 20 micromol/L higher than with the Vitros (enzymatic reaction). The results of this study show that the Spotchem analyzer is suitable for use in canine whole blood or plasma when small numbers of tests are to be performed and large analyzers are not available. PMID:16054888

  13. Regional cerebral incorporation of plasma (/sup 14/C)palmitate, and cerebral glucose utilization, in water-deprived Long-Evans and Brattleboro rats

    SciTech Connect

    Noronha, J.G.; Larson, D.M.; Rapoport, S.I.

    1989-03-01

    Regional rates of incorporation into brain of intravenously administered (/sup 14/C)palmitate and regional cerebral metabolic rates for glucose (rCMRglc) were measured in water-provided (WP) and water-deprived (WD) homozygous (DI) and heterozygous (HZ) Brattleboro rats, a mutant strain unable to synthesize vasopressin, and in the parent Long-Evans (LE) strain. Following 15 h or 4 days of water deprivation, rCMRglc was elevated threefold in the pituitary neural lobe of LE-WD and DI-WD as compared with LE-WP rats, and in the paraventricular nucleus of LE-WD, and the supraoptic nucleus of DI-WD rats. However, incorporation of (/sup 14/C)palmitate into these regions was not specifically altered. The results indicate that water deprivation for up to 4 days increases rCMRglc in some brain regions involved with vasopressin, but does not alter (/sup 14/C)palmitate incorporation into these regions. Incorporation of plasma (/sup 14/C)palmitate is independent of unlabeled plasma palmitate at brain regions which have an intact blood-brain barrier, but at nonbarrier regions falls according to saturation kinetics as cold plasma concentration rises, with a mean half-saturation constant (Km) equal to 0.136 mumol.ml-1.

  14. Prediction of gestational diabetes mellitus in the first trimester, comparison of fasting plasma glucose, two-step and one-step methods: a prospective randomized controlled trial.

    PubMed

    Yeral, M Ilkin; Ozgu-Erdinc, A Seval; Uygur, Dilek; Seckin, K Doga; Karsli, M Fatih; Danisman, A Nuri

    2014-08-01

    Our aim was to evaluate and compare the diagnostic performance of three methods commonly used for GDM screening: fasting plasma glucose (FPG), two-step 50 g glucose challenge test (GCT), and 75 g glucose tolerance test (GTT) in a randomized study design to predict GDM in the first trimester and determine the best approach in predicting GDM. In a non-blind, parallel-group prospective randomized controlled study; 736 singleton pregnant women underwent FPG testing in the first trimester and randomly assigned to two groups; two-step 50 g GCT and 75 g GTT. GDM diagnosis was made according to Carpenter-Coustan or ADA (American Diabetes Association) criteria in two-step 50 g GCT and 75 g GTT groups, respectively. Subsequent testing was performed by two-step 50 g GCT at 24-28 weeks for screen negatives. After excluding the women who were lost to follow-up or withdrawn as a result of pregnancy loss, 486 pregnant women were recruited in the study. The FPG, two-step GCT, and one-step GTT methods identified GDM in 25/486 (5.1 %), 15/248 (6.0 %), and 27/238 (11.3 %) women, respectively. Area under ROC curves were 0.623, 0.708, and 0.792, respectively. Sensitivities were 47.17, 68.18, and 87.1 %, respectively. Specificities were 77.37, 100, and 100 %, respectively. Positive predictive values were 20.33, 100, and 100 %, respectively. Negative predictive values were 92.29, 97, and 98.1 %, respectively. Until superior screening alternatives become available, the 75 g GTT may be preferred for GDM screening in the first trimester. PMID:24282036

  15. Enhanced Y1H Assays for Arabidopis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transcription regulation plays a key role in development and response to environment. To understand this mechanism, we need to know which transcription factor (TFs) would bind to which promoter, thus regulate their target gene expression. Yeast one-hybrid (Y1H) technique can be used to map this kind...

  16. (1)H-NMR-based discrimination of thermal and vinegar treated ginseng roots.

    PubMed

    Kim, So-Hyun; Hyun, Sun-Hee; Yang, Seung-Ok; Choi, Hyung-Kyoon; Lee, Boo-Yong

    2010-08-01

    To investigate the changes in nonvolatile metabolites of thermal and/or vinegar treated ginseng (TVG), samples prepared using various treatment conditions were analyzed using an (1)H-NMR-based metabolomics technique. The processing conditions of the ginseng in this study were 100, 140, and 180 degrees C with and without vinegar and the duration of exposure to each temperature was 10, 30, and 50 min, respectively. There was a clear separation in the score plots among various treatment conditions. Major compounds contributing to the separation of 50% methanol extracts of TVG with various process conditions were valine, lactate, alanine, arginine, glucose, fructose, and sucrose. As temperature increased, valine, arginine, glucose, fructose, and sucrose concentrations decreased, whereas lactate, glucose, and fructose increased in the vinegar-treated samples compared to non-vinegar-treated samples. The present study suggests the usefulness of an (1)H-NMR-based metabolomics approach to discriminate TVG samples, subjected to different processing conditions. PMID:20722913

  17. Common variants in the LAMA5 gene associate with fasting plasma glucose and serum triglyceride levels in a cohort of pre- and early pubertal children

    PubMed Central

    De Luca, Maria; Chandler-Laney, Paula C.; Wiener, Howard; Fernandez, Jose R.

    2012-01-01

    Laminins are glycoproteins found in basement membranes where they play a vital role in tissue architecture and cell behavior. Previously, we reported the association of two polymorphisms (rs659822 and rs944895) in the laminin alpha5 (LAMA5) gene with anthropometric traits, fasting lipid profile, and glucose levels in pre-menopausal women and elderly subjects. Furthermore, studies in mice showed that Lama5 is involved in organogenesis and placental function during pregnancy. The objective of this study was to investigate whether rs659822 and/or rs944895 are associated with inter-individual variability in birth weight as well as anthropometric traits and metabolic phenotypes in children. Two hundred and eighty nine healthy children aged 7–12 yr of European, Hispanic, and African-American ancestry were studied. Co-dominant models adjusted for genetic admixture, age, gender, and stages of puberty were used to test for the association of the polymorphisms with each trait. Our analysis showed significant associations of rs659822 with fasting plasma glucose levels (P = 0.0004) and of rs944895 with fasting serum triglycerides (P = 0.004) after Bonferroni correction for multiple testing. Our results corroborate our previous findings that genetic variants in LAMA5 contribute to variation in metabolic phenotypes and provide evidence that this may occur early in life.

  18. Effects of Topical Anesthetics on Behavior, Plasma Corticosterone, and Blood Glucose Levels after Tail Biopsy of C57BL/6NHSD Mice (Mus musculus).

    PubMed

    Dudley, Emily S; Johnson, Robert A; French, DeAnne C; Boivin, Gregory P

    2016-01-01

    Tail biopsy is a common procedure that is performed to obtain genetic material for determining genotype of transgenic mice. The use of anesthetics or analgesics is recommended, although identifying safe and effective drugs for this purpose has been challenging. We evaluated the effects of topical 2.5% lidocaine-2.5% prilocaine cream applied to the distal tail tip at 5 or 60 min before biopsy, immersion of the tail tip for 10 seconds in ice-cold 70% ethanol just prior to biopsy, and immersion of the tail tip in 0.5% bupivacaine for 30 s after biopsy. Mice were 7, 11, or 15 d old at the time of tail biopsy. Acute behavioral responses, plasma corticosterone, and blood glucose were measured after biopsy, and body weight and performance in elevated plus maze and open-field tests after weaning. Ice-cold ethanol prior to biopsy prevented acute behavioral responses to biopsy, and both ice-cold ethanol and bupivacaine prevented elevations in corticosterone and blood glucose after biopsy. Tail biopsy with or without anesthesia did not affect body weight or performance on elevated plus maze or open-field tests. We recommend the use of ice-cold ethanol for topical anesthesia prior to tail biopsy in mice 7 to 15 d old. PMID:27423152

  19. One-hour postload plasma glucose and risks of fatal coronary heart disease and stroke among nondiabetic men and women: the Chicago Heart Association Detection Project in Industry (CHA) Study.

    PubMed

    Orencia, A J; Daviglus, M L; Dyer, A R; Walsh, M; Greenland, P; Stamler, J

    1997-12-01

    Associations of baseline one-hour postload plasma glucose with 22-year coronary heart disease, stroke, cardiovascular diseases, and all cause mortality were assessed in five age-specific cohorts of nondiabetic men and women from the Chicago Heart Association Detection Project in Industry: 10,269 men ages 18-39 years; 7993 men ages 40-59 years; 1240 men ages 60-74 years; 6319 women ages 40-59 years; and 932 women ages 60-74 years. Plasma glucose was determined one hour after a 50-gram oral glucose load. Cox regression analyses were used to control for age and other covariates. Generally, higher glucose was significantly associated with mortality from coronary heart disease, stroke, cardiovascular diseases, and all cause mortality in men and women. This large longitudinal study provides evidence that one-hour postload plasma glucose in the absence of clinical diabetes at baseline apparently is an independent risk factor for fatal coronary heart disease and stroke in middle-aged and older nondiabetic men and women, and also for cardiovascular diseases and for all cause mortality. PMID:9449940

  20. Comparison of Plasma Glucose and Gut Hormone Levels Between Drinking Enteral Formula Over a Period of 5 and 20 Minutes in Japanese Patients With Type 2 Diabetes: A Pilot Study

    PubMed Central

    Kamiko, Kazunari; Aoki, Kazutaka; Kamiyama, Hiroshi; Taguri, Masataka; Terauchi, Yasuo

    2016-01-01

    Background A fast eating speed is reportedly associated with obesity, fatty liver, and metabolic syndrome. As a comparison of postprandial glucose levels after eating quickly or slowly has not been previously reported for Japanese patients with type 2 diabetes, we evaluated the impact of the fast or slow ingestion of an enteral formula (liquid meal) on glucose metabolism. Methods Ten Japanese patients with type 2 diabetes who had been hospitalized at our hospital were enrolled. All the subjects received an enteral formula for breakfast. The study was performed over a 2-day period in each subject (day 1: enteral formula was consumed over a 5-minute period; day 2: enteral formula was consumed over a 20-minute period). The subjects were requested to fast for at least 12 hours before eating breakfast, and blood samples were collected at 0, 30, 60, and 120 min after the start of breakfast. Results The areas under the curve (AUCs) of the plasma glucose, serum insulin, plasma active ghrelin, glucagon-like peptide-1 (GLP-1), plasma total glucose-dependent insulinotropic polypeptide (GIP), and serum total peptide YY (PYY) levels were not significantly changed by intake over a 5-minute or 20-minute period. Conclusions Eating quickly per se probably does not affect postprandial glucose excursions, but the increased energy intake resulting from eating quickly may increase the body weight and increase insulin resistance. Eating quickly may increase energy intake and worsen long-term metabolic parameters.

  1. Effects of Beak Trimming, Stocking Density and Sex on Carcass Yield, Carcass Components, Plasma Glucose and Triglyceride Levels in Large White Turkeys

    PubMed Central

    Kiraz, Selahattin

    2015-01-01

    This study was conducted to determine the effects of beak trimming, stocking density (D) and sex (S) on live weight (LW), carcass yield and its component, and plasma glucose (PG) and triglyceride levels in Large White turkeys. To accomplish this aims, totally 288 d old large white turkey chicks (144 in each sex) were used. Beaks of 77 male and female poults were trimmed when 8 d old with an electrical beak trimmer. The birds were fed by commercial turkey rasion. Experiment was designed as 2 × 2 × 2 factorial arrangement with 3 replications in each group. Beak trimming and stocking density did not affect live weight, carcass composition and its components. The higher LW and carcass weight observed in trimmed groups. As expected, male birds are heavier than female, and carcass percentage (CP) would be adverse. However, in this study, CP of male was higher in trimmed, in 0.25 m2/bird. (D) × sex (S) interaction had an effect on both CP and thigh weights (p<0.05). Significantly D × S was observed in LW, CP and PG. The weight of carcass and its some components were higher in male. S × D interaction had an effect on plasma glucose level (p<0.05). Triglyceride level was affected (p<0.05) by sex. Significant relationships were found between percentage of thighs (r=0.447, p<0.01) and percentage of breast (r=0.400, p<0.01). According to this study, it can be said that trimming is useful with density of 0.25 m2/bird in turkey fattening. PMID:26877630

  2. Blood plasma magnesium, potassium, glucose, and immunoreactive insulin changes in cows moved abruptly from barn feeding to early spring pasture

    SciTech Connect

    Miller, J.K.; Madsen, F.C.; Lentz, D.E.; Wong, W.O.; Ramsey, N.; Tysinger, C.E.; Hansard, S.L.

    1980-07-01

    Cations and immunoreactive insulin in plasma were measured in 35 lactating cows moved abruptly to early spring pasture. After change of cows from grass-clover hay to fescue-bluegrass pasture containing 22 to 31 g potassium/kg dry matter, immunoreactive insulin of 5 Holstein cows increased 30% in 5 days and averaged 45% above prepasture concentrations for 40 days. Magnesium averaged 44% below prepasture content of plasma during this period and was correlated negatively with potassium -.17 and immunoreactive insulin -.37. Thirty Hereford cows were changed from corn silage and grass-clover hay to wheat-rye pasture containing 3.06% potassium in the dry matter. Each day on pasture, 10 cows each were fed 2.3 kg cornmeal, 10 were given 30 g magnesium oxide by capsule, and 10 were given no supplement. After unsupplemented cows were moved to pasture, immunoreactive insulin rose 51% in 8 days and plasma magnesium fell 24%. Both supplements reduced immunoreactive insulin, but magnesium was maintained higher by magnesium oxide than by cornmeal. Injection of two Holstein cows with insulin (2 IU/kg body weight) reduced plasma concentrations of both potassium and mgnesium 20% below that of two cows injected with only physiological saline. Whether elevated plasma insulin may accelerate development of hypomagnesemia in cattle on spring pasture with relatively high potassium content has not been established.

  3. First-pass uptake and oxidation of glucose by the splanchnic tissue in young goats fed soy protein-based milk diets with or without amino acid supplementation: glucose metabolism in goat kids after soy feeding.

    PubMed

    Schönhusen, U; Junghans, P; Flöter, A; Steinhoff-Wagner, J; Görs, S; Schneider, F; Metges, C C; Hammon, H M

    2013-04-01

    The study was designed to examine whether feeding soy protein isolate as partial replacement of casein (CN) affects glucose metabolism in young goats and whether effects may be ameliorated by supplementation of those AA known to be lower concentrated in soy than in CN. Goat kids (d 20 of age) were fed comparable milk protein diets, in which 50% of the crude protein was either CN (control, CON), soy protein isolate (SPI), or soy protein isolate supplemented with AA (SPIA) for 43 d (n=8 per group). On d 62 of age, a single bolus dose of d-[(13)C6]glucose (10mg/kg of BW) was given with the morning diet, and simultaneously, a single bolus dose of d-[6,6-(2)H2]glucose (5mg/kg of BW) was injected into a jugular vein. Blood samples were collected between -30 and +420 min relative to the tracer administration to measure the (13)C and (2)H enrichments of plasma glucose and the (13)C enrichment of blood CO2. Glucose first-pass uptake by the splanchnic tissues was calculated from the rate of appearance of differentially labeled glucose tracer in plasma. Glucose oxidation was calculated from (13)C enrichment in blood CO2. In addition, plasma concentrations of triglycerides, nonesterified fatty acids, glucose, insulin, and glucagon were measured. On d 63 of age, kids were killed and jejunal mucosa and liver samples were collected to measure lactase mRNA levels and lactase and maltase activities in the jejunum and activities of pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK) in the liver. Basal plasma glucose concentration tended to be higher in the CON than the SPIA group, whereas basal insulin was higher in the CON group than the SPI and SPIA groups, and glucagon was higher in the CON than the SPIA group. Plasma glucose and insulin concentrations increased during the first hour after feeding, whereas plasma glucagon increased immediately after feeding and after 1h of feeding. First-pass uptake and glucose oxidation were not affected by diet. Maltase

  4. Conglutin gamma, a lupin seed protein, binds insulin in vitro and reduces plasma glucose levels of hyperglycemic rats.

    PubMed

    Magni, Chiara; Sessa, Fabio; Accardo, Elena; Vanoni, Marco; Morazzoni, Paolo; Scarafoni, Alessio; Duranti, Marcello

    2004-11-01

    This work describes the in vitro interaction between a lupin seed protein, namely, conglutin gamma, and insulin. The binding to an insulin-immobilized matrix occurs in the pH range from 7.5 to 4.2 and is strongly affected by ionic strength, suggesting that it is driven primarily by electrostatic interactions. The quantitative parameters of the binding were determined by surface plasmon resonance. On the basis of the conditions required for the interaction to take place and the quantitative binding parameters, it appeared that the interaction is specific, despite the fact that the origin of the two protein molecules is completely different. The effect of the oral administration of conglutin gamma on the glycemic levels of rats subjected to glucose overloading was a statistically significant reduction in glycemia comparable to that of metformin, a well-known glucose lowering drug. These findings represent the first molecular evidence of the possible use of a legume protein in the control of glycemia. PMID:15590267

  5. Optimal Cut-Off Points of Fasting Plasma Glucose for Two-Step Strategy in Estimating Prevalence and Screening Undiagnosed Diabetes and Pre-Diabetes in Harbin, China

    PubMed Central

    Sun, Bo; Lan, Li; Cui, Wenxiu; Xu, Guohua; Sui, Conglan; Wang, Yibaina; Zhao, Yashuang; Wang, Jian; Li, Hongyuan

    2015-01-01

    To identify optimal cut-off points of fasting plasma glucose (FPG) for two-step strategy in screening abnormal glucose metabolism and estimating prevalence in general Chinese population. A population-based cross-sectional study was conducted on 7913 people aged 20 to 74 years in Harbin. Diabetes and pre-diabetes were determined by fasting and 2 hour post-load glucose from the oral glucose tolerance test in all participants. Screening potential of FPG, cost per case identified by two-step strategy, and optimal FPG cut-off points were described. The prevalence of diabetes was 12.7%, of which 65.2% was undiagnosed. Twelve percent or 9.0% of participants were diagnosed with pre-diabetes using 2003 ADA criteria or 1999 WHO criteria, respectively. The optimal FPG cut-off points for two-step strategy were 5.6 mmol/l for previously undiagnosed diabetes (area under the receiver-operating characteristic curve of FPG 0.93; sensitivity 82.0%; cost per case identified by two-step strategy ¥261), 5.3 mmol/l for both diabetes and pre-diabetes or pre-diabetes alone using 2003 ADA criteria (0.89 or 0.85; 72.4% or 62.9%; ¥110 or ¥258), 5.0 mmol/l for pre-diabetes using 1999 WHO criteria (0.78; 66.8%; ¥399), and 4.9 mmol/l for IGT alone (0.74; 62.2%; ¥502). Using the two-step strategy, the underestimates of prevalence reduced to nearly 38% for pre-diabetes or 18.7% for undiagnosed diabetes, respectively. Approximately a quarter of the general population in Harbin was in hyperglycemic condition. Using optimal FPG cut-off points for two-step strategy in Chinese population may be more effective and less costly for reducing the missed diagnosis of hyperglycemic condition. PMID:25785585

  6. Optimal cut-off points of fasting plasma glucose for two-step strategy in estimating prevalence and screening undiagnosed diabetes and pre-diabetes in Harbin, China.

    PubMed

    Bao, Chundan; Zhang, Dianfeng; Sun, Bo; Lan, Li; Cui, Wenxiu; Xu, Guohua; Sui, Conglan; Wang, Yibaina; Zhao, Yashuang; Wang, Jian; Li, Hongyuan

    2015-01-01

    To identify optimal cut-off points of fasting plasma glucose (FPG) for two-step strategy in screening abnormal glucose metabolism and estimating prevalence in general Chinese population. A population-based cross-sectional study was conducted on 7913 people aged 20 to 74 years in Harbin. Diabetes and pre-diabetes were determined by fasting and 2 hour post-load glucose from the oral glucose tolerance test in all participants. Screening potential of FPG, cost per case identified by two-step strategy, and optimal FPG cut-off points were described. The prevalence of diabetes was 12.7%, of which 65.2% was undiagnosed. Twelve percent or 9.0% of participants were diagnosed with pre-diabetes using 2003 ADA criteria or 1999 WHO criteria, respectively. The optimal FPG cut-off points for two-step strategy were 5.6 mmol/l for previously undiagnosed diabetes (area under the receiver-operating characteristic curve of FPG 0.93; sensitivity 82.0%; cost per case identified by two-step strategy ¥261), 5.3 mmol/l for both diabetes and pre-diabetes or pre-diabetes alone using 2003 ADA criteria (0.89 or 0.85; 72.4% or 62.9%; ¥110 or ¥258), 5.0 mmol/l for pre-diabetes using 1999 WHO criteria (0.78; 66.8%; ¥399), and 4.9 mmol/l for IGT alone (0.74; 62.2%; ¥502). Using the two-step strategy, the underestimates of prevalence reduced to nearly 38% for pre-diabetes or 18.7% for undiagnosed diabetes, respectively. Approximately a quarter of the general population in Harbin was in hyperglycemic condition. Using optimal FPG cut-off points for two-step strategy in Chinese population may be more effective and less costly for reducing the missed diagnosis of hyperglycemic condition. PMID:25785585

  7. Metabolic profiles using (1)H-nuclear magnetic resonance spectroscopy in postpartum dairy cows with ovarian inactivity.

    PubMed

    Xu, Chuchu; Xia, Cheng; Sun, Yuhang; Xiao, Xinhuan; Wang, Gang; Fan, Ziling; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Yang, Wei

    2016-10-01

    To understand the differences in metabolic changes between cows with ovarian inactivity and estrus cows, we selected cows at 60-90 days postpartum from an intensive dairy farm. According to clinical manifestations, B-ultrasound scan, rectal examination, 10 cows were assigned to the estrus group (A) and 10 to the ovarian inactivity group (B). All plasma samples were analyzed by (1)H-nuclear magnetic resonance spectroscopy to compare plasma metabolomic profiles between the groups. We used multivariate pattern recognition to screen for different metabolites in plasma of anestrus cows. Compared with normal estrous cows, there were abnormalities in 12 kinds of metabolites in postpartum cows with ovarian inactivity (|r|> 0.602), including an increase in acetic acid (r = -0.817), citric acid (r = -0.767), and tyrosine (r = -0.714), and a decrease in low-density lipoprotein (r = 0.820), very low-density lipoprotein (r = 0.828), lipids (r = 0.769), alanine (r = 0.816), pyruvate (r = 0.721), creatine (r = 0.801), choline (r = 0.639), phosphorylcholine (r = 0.741), and glycerophosphorylcholine (r = 0.881). These metabolites were closely related to abnormality of glucose, amino acid, lipoprotein and choline metabolism, which may disturb the normal estrus. The decrease in plasma creatine and the increase in tyrosine were new changes for ovarian inactivity of postpartum cows. The decrease in plasma creatine and choline and the increase in tyrosine and p-hydroxyphenylalanine in cows with ovarian inactivity provide new directions for research on the mechanism of ovarian inactivity in cows. PMID:27291083

  8. Naturally high plasma glucose levels in mourning doves (Zenaida macroura) do not lead to high levels of reactive oxygen species in the vasculature.

    PubMed

    Smith, Christina L; Toomey, Matthew; Walker, Benjimen R; Braun, Eldon J; Wolf, Blair O; McGraw, Kevin; Sweazea, Karen L

    2011-06-01

    Plasma glucose (P(Glu)) concentrations in birds are 1.5-2 times higher than those of mammals of similar body mass. In mammals, sustained elevations of P(Glu) lead to oxidative stress and free radical-mediated scavenging of endogenous vasodilators (e.g., nitric oxide), contributing to elevated blood pressure. Despite the relatively high P(Glu) levels in birds, they appear resistant to the development of oxidative stress in tissues such as the heart, brain and kidneys. To our knowledge no information exists on oxidative stress susceptibility in the resistance vasculature of birds. Therefore, we compared endogenous antioxidant mechanisms in the resistance vasculature of mourning doves (MODO; Zenaida macroura) and rats (Rattus norvegicus). Reactive oxygen species (ROS) were assessed with the fluorescent indicator 7'-dichlorodihydrofluorescein diacetate, acetyl ester in mesenteric arteries from rats and wild-caught MODO. Despite having significantly higher P(Glu) than rats, there were no significant differences in ROS levels between mesenteric arteries from rats or doves. Although superoxide dismutase and catalase activities were lower in the plasma, total antioxidant capacity, uric acid, vitamin E (α-tocopherol), and carotenoids (lutein and zeaxanthin) were significantly higher in MODO than in rats. Thus, compared to rats, MODO have multiple circulating antioxidants that may prevent the development of oxidative stress in the vasculature. PMID:21600747

  9. Phenotype and Age Differences in Blood Gas Characteristics, Electrolytes, Hemoglobin, Plasma Glucose and Cortisol in Female Squirrel Monkeys

    NASA Technical Reports Server (NTRS)

    Brizzee, K. R.; Ordy, J. M.; Dunlap, W. P.; Kendrick, R.; Wengenack, T. M.

    1988-01-01

    Due to its small size, lower cost, tractable nature, successful breeding in captivity and its status near the middle of the primate phylogenetic scale, the squirrel monkey has become an attractive primate model for basic and biomedical research. Although the squirrel monkey now is being used more extensively in many laboratories with diverse interests, only fragmentary reports have been published regarding basic physiological characteristics, or baseline blood reference values of different phenotypes, particularly blood gases, hematology and serum chemical constituents. It is becoming recognized increasingly that these baseline blood reference values are important not only in the care and maintenance of the squirrel monkey, but are critical for assessing normal physiological status, as well as the effects of various experimental treatments. The purpose of this study was to compare differences in blood gases, electrolytes, hematology, blood glucose and cortisol among young and old Bolivian (Roman type) and Colombian (Gothic type) phenotypes of the squirrel monkey.

  10. Revealing Potential Biomarkers of Functional Dyspepsia by Combining 1H NMR Metabonomics Techniques and an Integrative Multi-objective Optimization Method

    PubMed Central

    Wu, Qiaofeng; Zou, Meng; Yang, Mingxiao; Zhou, Siyuan; Yan, Xianzhong; Sun, Bo; Wang, Yong; Chang, Shyang; Tang, Yong; Liang, Fanrong; Yu, Shuguang

    2016-01-01

    Metabonomics methods have gradually become important auxiliary tools for screening disease biomarkers. However, recognition of metabolites or potential biomarkers closely related to either particular clinical symptoms or prognosis has been difficult. The current study aims to identify potential biomarkers of functional dyspepsia (FD) by a new strategy that combined hydrogen nuclear magnetic resonance (1H NMR)-based metabonomics techniques and an integrative multi-objective optimization (LPIMO) method. First, clinical symptoms of FD were evaluated using the Nepean Dyspepsia Index (NDI), and plasma metabolic profiles were measured by 1H NMR. Correlations between the key metabolites and the NDI scores were calculated. Then, LPIMO was developed to identify a multi-biomarker panel by maximizing diagnostic ability and correlation with the NDI score. Finally, a KEGG database search elicited the metabolic pathways in which the potential biomarkers are involved. The results showed that glutamine, alanine, proline, HDL, β-glucose, α-glucose and LDL/VLDL levels were significantly altered in FD patients. Among them, phosphatidycholine (PtdCho) and leucine/isoleucine (Leu/Ile) were positively and negatively correlated with the NDI Symptom Index (NDSI) respectively. Our procedure not only significantly improved the credibility of the biomarkers, but also demonstrated the potential of further explorations and applications to diagnosis and treatment of complex disease. PMID:26743458

  11. Nutrient Excess and AMPK Downregulation in Incubated Skeletal Muscle and Muscle of Glucose Infused Rats

    PubMed Central

    Valentine, Rudy J.; Petrocelli, Robert; Schultz, Vera; Brandon, Amanda; Cooney, Gregory J.; Kraegen, Edward W.; Ruderman, Neil B.; Saha, Asish K.

    2015-01-01

    We have previously shown that incubation for 1h with excess glucose or leucine causes insulin resistance in rat extensor digitorum longus (EDL) muscle by inhibiting AMP-activated protein kinase (AMPK). To examine the events that precede and follow these changes, studies were performed in rat EDL incubated with elevated levels of glucose or leucine for 30min-2h. Incubation in high glucose (25mM) or leucine (100μM) significantly diminished AMPK activity by 50% within 30min, with further decreases occurring at 1 and 2h. The initial decrease in activity at 30min coincided with a significant increase in muscle glycogen. The subsequent decreases at 1h were accompanied by phosphorylation of αAMPK at Ser485/491, and at 2h by decreased SIRT1 expression and increased PP2A activity, all of which have previously been shown to diminish AMPK activity. Glucose infusion in vivo, which caused several fold increases in plasma glucose and insulin, produced similar changes but with different timing. Thus, the initial decrease in AMPK activity observed at 3h was associated with changes in Ser485/491 phosphorylation and SIRT1 expression and increased PP2A activity was a later event. These findings suggest that both ex vivo and in vivo, multiple factors contribute to fuel-induced decreases in AMPK activity in skeletal muscle and the insulin resistance that accompanies it. PMID:25996822

  12. Changes in plasma metabolites and glucose homeostasis during omega-3 polyunsaturated fatty acid supplementation in women with polycystic ovary syndrome

    PubMed Central

    Karakas, Sidika E.; Perroud, Bertrand; Kind, Tobias; Palazoglu, Mine; Fiehn, Oliver

    2016-01-01

    Background Both fish (FO) and flaxseed oils (FLX) are n-3 polyunsaturated fatty acids (PUFA). Fish oil contains long chain while FLX contains essential n-3 PUFA. We demonstrated that FO altered insulin secretion and resistance in polycystic ovary syndrome (PCOS) women but FLX did not. Surprisingly, the effects of FO were similar to those of the n-6 PUFA-rich soybean oil (SBO). Since increased branched chain (BCAA) and aromatic amino acids (AA) affect insulin secretion and resistance, we investigated whether FO, FLX and /or SBO affect plasma metabolites, especially AA. Methods and findings In this six-week, randomized, 3-parallel arm, double-blinded study, 54 women received 3.5 g/day FO, FLX or SBO. In 51 completers (17 from each arm), fasting plasma metabolites were measured at the beginning and at the end. As compared to FLX, FO and SBO increased insulin response and resistance as well as several BCAA and aromatic AA. Pathway analysis indicated that FO exerted the largest biochemical impact, affecting AA degradation and biosynthesis, amine, polyamine degradation and alanine, glycine, l-carnitine biosynthesis and TCA cycle, while FLX had minimal impact affecting only alanine biosynthesis and l-cysteine degradation. Conclusion Effects of FO and SBO on plasma AA were similar and differed significantly from those of the FLX. The primary target of dietary PUFA is not known. Dietary PUFA may influence insulin secretion and resistance directly and alter plasma AA indirectly. Alternatively, as a novel concept, dietary PUFA may directly affect AA metabolism and the changes in insulin secretion and resistance may be secondary. PMID:27182493

  13. The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Preserves Endothelial Function in Mesenteric Arteries from Type 1 Diabetic Rats without Decreasing Plasma Glucose

    PubMed Central

    Salheen, Salheen M.; Panchapakesan, Usha; Pollock, Carol A.; Woodman, Owen L.

    2015-01-01

    The aim of the study was to investigate the effect of the DPP-4 inhibitor linagliptin on the mechanism(s) of endothelium-dependent relaxation in mesenteric arteries from STZ-induced diabetic rats. Both normal and diabetic animals received linagliptin (2 mg/kg) daily by oral gavage for a period of 4 weeks. To measure superoxide generation in mesenteric arteries, lucigenin-enhanced chemiluminescence was used. ACh-induced relaxation of mesenteric arteries was assessed using organ bath techniques and Western blotting was used to investigate protein expression. Pharmacological tools (1μM TRAM-34, 1μM apamin, 100 nM Ibtx, 100 μM L-NNA, 10 μM ODQ) were used to distinguish between NO and EDH-mediated relaxation. Linagliptin did not affect plasma glucose, but did decrease vascular superoxide levels. Diabetes reduced responses to ACh but did not affect endothelium-independent responses to SNP. Linagliptin improved endothelial function indicated by a significant increase in responses to ACh. Diabetes impaired the contribution of both nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) to endothelium-dependent relaxation and linagliptin treatment significantly enhanced the contribution of both relaxing factors. Western blotting demonstrated that diabetes also increased expression of Nox2 and decreased expression and dimerization of endothelial NO synthase, effects that were reversed by linagliptin. These findings demonstrate treatment of type 1 diabetic rats with linagliptin significantly reduced vascular superoxide levels and preserved both NO and EDH-mediated relaxation indicating that linagliptin can improve endothelial function in diabetes independently of any glucose lowering activity. PMID:26618855

  14. Fasting and diet content affect stress-induced changes in plasma glucose and cortisol in Juvenile chinook salmon. [Oncorhynchus tshawytscha

    SciTech Connect

    Barton, B.A.; Schreck, C.B. ); Fowler, L.G. )

    1988-01-01

    Juvenile chinook salmon (Oncorhynchus tshawytscha) reared on low-, medium-, or high-lipid diets for 18 weeks were either kept on their respective diets or fasted for 20 d; then they were subjected to a 30-s handling stress or to handling plus continuous confinement. In fish that were handled but not confined, poststress hyperglycemia was greatest in fed fish that received the high-lipid diet and was generally lower in fasted than in fed fish. Plasma cortisol elevations in response to handling or handling plus confinement stress were not appreciably affected by diet type or fasting. The result indicated that prior feeding regimes and the types of diet fed should be considered when one is interpreting the magnitude of hyperglycemic stress responses in juvenile chinook salmon.

  15. Differential control of glucoregulatory hormone response and glucose metabolism by NMDA and kainate.

    PubMed

    Yousef, K A; Tepper, P G; Molina, P E; Abumrad, N N; Lang, C H

    1994-01-14

    The aim of the present study was to elucidate the effect of kainate and N-methyl-D-aspartate (NMDA), two different excitatory amino acid (EAA) agonists, on glucoregulatory hormone production and whole body glucose metabolism. Rates of hepatic glucose production (HGP) and peripheral glucose utilization (GU) were assessed in overnight fasted, catheterized, conscious rats using [3-3H]glucose. At the highest dose of kainate examined (16 mg/kg), glucose levels increased 97% after 1 h; thereafter, glucose fell towards basal values but was still elevated 25% at the end of the 3 h experiment. This hyperglycemia resulted from a rapid increase in HGP that exceeded an increased rate of GU. Both HGP and GU were elevated 86% throughout the final 2 h of the experiment. NMDA induced changes in glucose flux that were qualitatively similar, yet of smaller magnitude and of shorter duration, than those produced by kainate. Kainate-induced increases in glucose metabolism were associated with an early transient hyperinsulinemia followed by a period of insulinopenia, and sustained increases in the plasma concentrations of glucagon, corticosterone, epinephrine and norepinephrine. In contrast, sustained increases in glucagon and catecholamines, as well as the late hypoinsulinemia were not detected in NMDA-treated rats. Adrenergic blockade attenuated the kainate- but not the NMDA-induced increase in glucose metabolism. These results indicate that EAA agonists that bind preferentially to different receptor subtypes produce qualitatively similar changes in glucose metabolism. Whereas the increased HGP in kainate-injected rats was associated with sustained elevations in glucagon, catecholamines and corticosterone, NMDA only transiently elevated circulating glucocorticoid levels, suggesting a different mechanism of action. These data, support the involvement of EAA in various aspects of glucoregulation. PMID:8156383

  16. Reduced glucose utilization underlies seizure protection with dietary therapy in epileptic EL mice.

    PubMed

    Meidenbauer, Joshua J; Roberts, Mary F

    2014-10-01

    Dietary therapy has been used to treat many individuals with epilepsy whose seizures are refractory to antiepileptic drugs. The mechanisms for how dietary therapy confers seizure protection are currently not well understood. We evaluated the acute effects of glucose and β-hydroxybutyrate (the major circulating ketone body) in conferring seizure protection to the EL mouse, a model of multifactorial idiopathic generalized epilepsy. EL mice were fed either an unrestricted standard diet or a calorie-restricted standard diet to achieve a body weight reduction of 20-23%. D-Glucose, 2-deoxy-D-glucose, and β-hydroxybutyrate were supplemented in the drinking water of calorie-restricted mice for 2.5 h prior to seizure testing to simulate the effect of increased glucose availability, decreased glucose utilization, and increased ketone availability, respectively. Seizure susceptibility, body weight, plasma glucose, and β-hydroxybutyrate were measured over a nine-week treatment period. Additionally, excitatory and inhibitory amino acids were measured in the brains of mice using (1)H NMR. Glutamate decarboxylase activity was also measured to evaluate the connection between dietary therapy and brain metabolism. We found that lowering of glucose utilization is necessary to confer seizure protection with long-term (>4 weeks) calorie restriction, whereas increased ketone availability did not affect seizure susceptibility. In the absence of long-term calorie restriction, however, reduced glucose utilization and increased ketone availability did not affect seizure susceptibility. Brain excitatory and inhibitory amino acid content did not change with treatment, and glutamate decarboxylase activity was not associated with seizure susceptibility. We demonstrated that reduced glucose utilization is necessary to confer seizure protection under long-term calorie restriction in EL mice, while acute ketone supplementation did not confer seizure protection. Further studies are needed to

  17. A 1H-NMR-Based Metabonomic Study on the Anti-Depressive Effect of the Total Alkaloid of Corydalis Rhizoma.

    PubMed

    Wu, Hongwei; Wang, Peng; Liu, Mengting; Tang, Liying; Fang, Jing; Zhao, Ye; Zhang, Yi; Li, Defeng; Xu, Haiyu; Yang, Hongjun

    2015-01-01

    Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, β-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics. PMID:26035102

  18. Glucose cycling in islets from healthy and diabetic rats

    SciTech Connect

    Khan, A.; Chandramouli, V.; Ostenson, C.G.; Loew, H.L.; Landau, B.R.; Efendic, S. )

    1990-04-01

    Pancreatic islets from healthy (control) and neonatally streptozocin-induced diabetic (STZ-D) rats, a model for non-insulin-dependent diabetes mellitus, were incubated with {sup 3}H{sub 2}O and 5.5 or 16.7 mM glucose. At 5.5 mM glucose, no detectable ({sup 3}H)glucose was formed. At 16.7 mM, 2.2 patom.islet-1.h-1 of {sup 3}H was incorporated into glucose by the control islets and 5.4 patom.islet-1.h-1 by STZ-D islets. About 75% of the {sup 3}H was bound to carbon-2 of the glucose. Glucose utilization was 35.3 pmol.islet-1.h-1 by the control and 19.0 pmol.islet-1.h-1 by the STZ-D islets. Therefore, 4.5% of the glucose-6-phosphate formed by the control islets and 15.7% by the STZ-D islets was dephosphorylated. This presumably occurred in the beta-cells of the islets catalyzed by glucose-6-phosphatase. An increased glucose cycling, i.e., glucose----glucose-6-phosphate----glucose, in islets of STZ-D rats may contribute to the decreased insulin secretion found in these animals.

  19. Real-time monitoring of glucose-6-phosphate dehydrogenase activity using liquid droplet arrays and its application to human plasma samples.

    PubMed

    Jung, Se-Hui; Ji, Su-Hyun; Han, Eun-Taek; Park, Won Sun; Hong, Seok-Ho; Kim, Young-Myeong; Ha, Kwon-Soo

    2016-05-15

    Glucose-6-phosphate dehydrogenase (G6PD) regulates nicotinamide adenine dinucleotide phosphate (NADPH) levels and is related to the pathogenesis of various diseases, including G6PD deficiency, type 2 diabetes, aldosterone-induced endothelial dysfunction, and cancer. Therefore, a highly sensitive array-based assay for determining quantitative G6PD activity is required. Here, we developed an on-chip G6PD activity assay using liquid droplet fluorescence arrays. Quantitative G6PD activity was determined by calculating reduced resorufin concentrations in liquid droplets. The limit of detection (LOD) of this assay was 0.162 mU/ml (2.89 pM), which is much more sensitive than previous assays. We used our activity assay to determine kinetic parameters, including Michaelis-Menten constants (Km) and maximum rates of enzymatic reaction (Vmax) for NADP(+) and G6P, and half-maximal inhibitory concentrations (IC50). We successfully applied this new assay to determine G6PD activity in human plasma from normal healthy individuals (n=30) and patients with inflammation (n=30). The inflammatory group showed much higher G6PD activities than did the normal group (p<0.001), with a high area under the curve value of 0.939. Therefore, this new activity assay has the potential to be used for diagnosis of G6PD-associated diseases and utilizing kinetic studies. PMID:26802575

  20. Abnormal oral glucose tolerance and glucose malabsorption after vagotomy and pyloroplasty. A tracer method for measuring glucose absorption rates

    SciTech Connect

    Radziuk, J.; Bondy, D.C.

    1982-11-01

    The mechanisms underlying the abnormal glucose tolerance in patients who had undergone vagotomy and pyloroplasty were investigated by measuring the rates of absorption of ingested glucose and the clearance rate of glucose using tracer methods. These methods are based on labeling a 100-g oral glucose load with (1-/sup 14/C)glucose and measuring glucose clearance using plasma levels of infused (3-/sup 3/H)glucose. The rate of appearance of both ingested and total glucose is then calculated continuously using a two-compartment model of glucose kinetics. It was found that about 30% of the ingested glucose (100 g) failed to appear in the systemic circulation. That this was due to malabsorption was confirmed using breath-hydrogen analysis. The absorption period is short (101 +/- 11 min) compared with normal values but the clearance of glucose is identical to that in control subjects, and it peaks 132 +/- 7 min after glucose loading. The peak plasma insulin values were more than four times higher in patients than in normal subjects, and this may afford an explanation of rates of glucose clearance that are inappropriate for the short absorption period. The combination of glucose malabsorption and this clearance pattern could yield the hypoglycemia that may be observed in patients after gastric surgery.

  1. Metabolomic differentiation of Cannabis sativa cultivars using 1H NMR spectroscopy and principal component analysis.

    PubMed

    Choi, Young Hae; Kim, Hye Kyong; Hazekamp, Arno; Erkelens, Cornelis; Lefeber, Alfons W M; Verpoorte, Robert

    2004-06-01

    The metabolomic analysis of 12 Cannabis sativa cultivars was carried out by 1H NMR spectroscopy and multivariate analysis techniques. Principal component analysis (PCA) of the 1H NMR spectra showed a clear discrimination between those samples by principal component 1 (PC1) and principal component 3 (PC3) in cannabinoid fraction. The loading plot of PC value obtained from all 1)H NMR signals shows that Delta9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) are important metabolites to differentiate the cultivars from each other. The discrimination of the cultivars could also be obtained from a water extract containing carbohydrates and amino acids. The level of sucrose, glucose, asparagine, and glutamic acid are found to be major discriminating metabolites of these cultivars. This method allows an efficient differentiation between cannabis cultivars without any prepurification steps. PMID:15217272

  2. Observation of 1H-13C and 1H-1H proximities in a paramagnetic solid by NMR at high magnetic field under ultra-fast MAS.

    PubMed

    Li, Shenhui; Trébosc, Julien; Lafon, Olivier; Zhou, Lei; Shen, Ming; Pourpoint, Frédérique; Amoureux, Jean-Paul; Deng, Feng

    2015-02-01

    The assignment of NMR signals in paramagnetic solids is often challenging since: (i) the large paramagnetic shifts often mask the diamagnetic shifts specific to the local chemical environment, and (ii) the hyperfine interactions with unpaired electrons broaden the NMR spectra and decrease the coherence lifetime, thus reducing the efficiency of usual homo- and hetero-nuclear NMR correlation experiments. Here we show that the assignment of (1)H and (13)C signals in isotopically unmodified paramagnetic compounds with moderate hyperfine interactions can be facilitated by the use of two two-dimensional (2D) experiments: (i) (1)H-(13)C correlations with (1)H detection and (ii) (1)H-(1)H double-quantum↔single-quantum correlations. These methods are experimentally demonstrated on isotopically unmodified copper (II) complex of l-alanine at high magnetic field (18.8 T) and ultra-fast Magic Angle Spinning (MAS) frequency of 62.5 kHz. Compared to (13)C detection, we show that (1)H detection leads to a 3-fold enhancement in sensitivity for (1)H-(13)C 2D correlation experiments. By combining (1)H-(13)C and (1)H-(1)H 2D correlation experiments with the analysis of (13)C longitudinal relaxation times, we have been able to assign the (1)H and (13)C signals of each l-alanine ligand. PMID:25557861

  3. Glucose kinetics in infants of diabetic mothers

    SciTech Connect

    Cowett, R.M.; Susa, J.B.; Giletti, B.; Oh, W.; Schwartz, R.

    1983-08-01

    Glucose kinetic studies were performed to define the glucose turnover rate with 78% enriched D-(U-13C) glucose by the prime constant infusion technique at less than or equal to 6 hours of age in nine infants of diabetic mothers (four insulin-dependent and five chemical diabetic patients) at term. Five normal infants were studied as control subjects. All infants received 0.9% saline intravenously during the study with the tracer. Fasting plasma glucose, insulin, and glucose13/12C ratios were measured during the steady state, and the glucose turnover rate was derived. The average plasma glucose concentration was similar during the steady state in the infants of the diabetic mothers and in the control infants, and the glucose turnover rate was not significantly different among the groups: 2.3 +/- 0.6 mg . kg-1 min-1 in infants of insulin-dependent diabetic patients; 2.4 +/- 0.4 mg . kg-1 min-1 in infants of chemical diabetic patients; and 3.2 +/- 0.3 mg . kg-1 min-1 in the control subjects. Good control of maternal diabetes evidenced by the normal maternal hemoglobin A1c and plasma glucose concentration at delivery and cord plasma glucose concentration resulted in glucose kinetic values in the infants of diabetic mothers that were indistinguishable from those of control subjects. The data further support the importance of good control of the diabetic state in the pregnant woman to minimize or prevent neonatal hypoglycemia.

  4. Crystalline 1H-1,2,3-triazol-5-ylidenes

    DOEpatents

    Bertrand, Guy; Gulsado-Barrios, Gregorio; Bouffard, Jean; Donnadieu, Bruno

    2016-08-02

    The present invention provides novel and stable crystalline 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of making 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of using 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes in catalytic reactions.

  5. Maturation of spermatozoa from rainbow trout (Oncorhynchus mykiss) sex-reversed females using artificial seminal plasma or glucose-methanol extender.

    PubMed

    Ciereszko, Andrzej; Dietrich, Grzegorz J; Nynca, Joanna; Dobosz, Stefan; Krom, Janusz

    2015-04-15

    Masculinized females (sex-reversed females) produce only homogametic spermatozoa (X) for fertilization which is desired for the production of all-female rainbow trout populations. The milt of sex-reversed females is of low quality and must be matured through extension in maturation solutions. The aim of this study was to compare the usefulness of glucose-methanol (GM) extender with artificial seminal plasma (ASP) extender for the maturation of milt of sex-reversed female rainbow trout. Milt suspensions were incubated at 4 °C for either 15 minutes (GM extender) or 120 minutes (ASP extender). Incubation of milt diluted in either the GM or ASP extender caused a significant (P < 0.05) increase in the percentage of sperm motility to 76.1 ± 10.9% and 74.7 ± 18.6% for GM and ASP, respectively, but no differences between both the extenders were found. Incubation also increased the average path velocity, straight line velocity, and linearity values of spermatozoa diluted with the GM extender; at the same time, none of the other parameters changed for ASP suspensions. Sperm diluted with ASP was characterized by higher curvilinear velocity and lateral head displacement values. Percentage of eyed embryos produced by fertilization using milt diluted in the GM extender amounted to 63.6 ± 16.4% and 67.2 ± 11.9% for sperm-to-egg ratio of 300,000:1 or 600,000:1, respectively and was lower (P < 0.05) compared with that of ASP extender (79.5 ± 5.8% and 80.3 ± 4.7% for sperm-to-egg ratio of 300,000:1 or 600,000:1, respectively). The results of our study clearly report that the mechanism of sperm maturation by the GM extender differs from that based on ASP. PMID:25638350

  6. Risk of Future Diabetes in Japanese People with High-normal Fasting Plasma Glucose Levels: A 4-Year Follow-up Study.

    PubMed

    Watanabe, Yoh; Eto, Tanenao; Taniguchi, Shotaro; Terauchi, Yasuo

    2016-01-01

    Objective There is no definite consensus regarding the treatment and guidance for individuals with high-normal fasting plasma glucose levels (FPG;100-109 mg/dL). The present study aimed to determine the risk factors for future diabetes in Japanese people with high-normal FPG. Methods Retrospective cohort studies were conducted from 2008 to 2012, including 15,097 individuals who underwent medical examinations. First, the participants were divided into normal FPG (n=13,065) and high-normal FPG (n=2,032) groups to compare the diabetes incidence. Second, the high FPG group was divided into diabetes onset (n=133) and non-diabetes onset (n=1,899) groups to compare the baseline values. Third, to determine the risk factors for future diabetes in the high-normal FPG group, multivariate analyses were conducted. Results The cumulative incidence during the mean follow-up of 4 years was 94/13,065 (0.72%) and 133/2,032 (6.55%) in the normal FPG and high-normal FPG groups, respectively. Within the high-normal FPG group, the baseline body mass index, waist circumference, triglycerides, FPG, alanine aminotransferase (ALT), and gamma-glutamyl transferase were significantly higher and high-density lipoprotein cholesterol (HDL-C) was significantly lower in the diabetes onset group than in the non-diabetes onset group. Obesity, abdominal obesity, hypertriglyceridemia, low HDL-C, and high ALT were significant risk factors for diabetes according to a multivariate analysis. Conclusion The high-normal FPG group had a higher risk of diabetes than the normal FPG group, particularly when accompanied with obesity, abdominal obesity, hypertriglyceridemia, low HDL-C, and high ALT. Thus, this high risk group should receive appropriate guidance for lifestyle changes to avoid developing diabetes at an early stage. PMID:27580535

  7. The Association between HbA1c, Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes

    PubMed Central

    Lind, Marcus; Tuomilehto, Jaakko; Uusitupa, Matti; Nerman, Olle; Eriksson, Johan; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Peltonen, Markku; Pivodic, Aldina; Lindström, Jaana

    2014-01-01

    Objective To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes. Design We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study. Setting Follow-up of clinical trial. Participants 504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c. Main Outcome Measure Relative risk of CVD. Results Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD. Conclusions and Relevance Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes. PMID:25285769

  8. Haemolymph from Mytilus galloprovincialis: Response to copper and temperature challenges studied by (1)H-NMR metabonomics.

    PubMed

    Digilio, Giuseppe; Sforzini, Susanna; Cassino, Claudio; Robotti, Elisa; Oliveri, Caterina; Marengo, Emilio; Musso, Davide; Osella, Domenico; Viarengo, Aldo

    2016-01-01

    Numerous studies on molluscs have been carried out to clarify the physiological roles of haemolymph serum proteins and haemocytes. However, little is known about the presence and functional role of the serum metabolites. In this study, Nuclear Magnetic Resonance (NMR) was used to assess whether changes of the metabolic profile of Mytilus galloprovincialis haemolymph may reflect alterations of the physiological status of the organisms due to environmental stressors, namely copper and temperature. Mussel haemolymph was taken from the posterior adductor muscle after a 4-day exposure to ambient (16°C) or high temperature (24°C) and in the absence or presence (5μg/L, 20μg/L, or 40μg/L) of sublethal copper (Cu(2+)). The total glutathione (GSH) concentration in the haemolymph of both control and treated mussels was minimal, indicating the absence of significant contaminations by muscle intracellular metabolites due to the sampling procedure. In the (1)H-NMR spectrum of haemolymph, 27 metabolites were identified unambiguously. The separate and combined effects of exposure to copper and temperature on the haemolymph metabolic profile were assessed by Principal Component Analysis (PCA) and Ranking-PCA multivariate analysis. Changes of the metabolomic profile due to copper exposure at 16°C became detectable at a dose of 20μg/L copper. Alanine, lysine, serine, glutamine, glycogen, glucose and protein aliphatics played a major role in the classification of the metabolic changes according to the level of copper exposition. High temperature (24°C) and high copper levels caused a coherent increase of a common set of metabolites (mostly glucose, serine, and lysine), indicating that the metabolic impairment due to high temperature is enforced by the presence of copper. Overall, the results demonstrate that, as for human blood plasma, the analysis of haemolymph metabolites represents a promising tool for the diagnosis of pollutant-induced stress syndrome in marine mussels

  9. Modelling the Relative Contribution of Fasting and Post-Prandial Plasma Glucose to HbA1c in Healthy and Type 2 Diabetic Subjects

    ERIC Educational Resources Information Center

    Ollerton, Richard L.; Luzio, Steven D.; Owens, David R.

    2004-01-01

    Glycated haemoglobin (HbA1c) is regarded as the gold standard of glucose homeostasis assessment in diabetes. There has been much discussion in recent medical literature of experimental results concerning the relative contribution of fasting and post-prandial glucose levels to the value of HbA1c. A mathematical model of haemoglobin glycation is…

  10. Restraint Stress Impairs Glucose Homeostasis Through Altered Insulin Signalling in Sprague-Dawley Rat.

    PubMed

    Morakinyo, Ayodele O; Ajiboye, Kolawole I; Oludare, Gabriel O; Samuel, Titilola A

    2016-01-01

    The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were exposed to one of the four different restraint stressors; 1 h, twice daily for a period of 7 days (S7D), 14 days (S14D) and 28 days (S28D). Glucose tolerance and insulin sensitivity were evaluated following the final stress exposure. ELISA were performed to assess the level of insulin and adiponectin as well as expression of INSR and GLUT4 protein in skeletal muscle. Plasma corticosterone level was also determined as a marker of stress exposure. Restraint stress for 7 days caused transient glucose intolerance, while S14D rats demonstrated increased glucose intolerance and insulin insensitivity. However, restraint stress for 28 days had no effect on glucose tolerance, but did cause an increase in glucose response to insulin challenge. The serum level of adiponectin was significantly (p< 0.05) lower compared with the control value while insulin remained unchanged except at in S28D rats that had a significant (p<0.05) increase. The expression of INSR and GLUT4 receptors were significantly (p< 0.05) decreased in the skeletal muscle of restraint stress exposed rats. There was a significant (p< 0.05) increase in the plasma corticosterone level of the stress rats compared with their control counterparts. Restraint stress caused glucose intolerance and insulin insensitivity in male Sprague-Dawley rats, which becomes accommodated with prolonged exposure and was likely related to the blunted insulin signalling in skeletal muscle. PMID:27574760

  11. Hematocrit and oxygenation dependence of blood (1)H(2)O T(1) at 7 Tesla.

    PubMed

    Grgac, Ksenija; van Zijl, Peter C M; Qin, Qin

    2013-10-01

    Knowledge of blood (1)H2O T1 is critical for perfusion-based quantification experiments such as arterial spin labeling and cerebral blood volume-weighted MRI using vascular space occupancy. The dependence of blood (1)H2O T1 on hematocrit fraction (Hct) and oxygen saturation fraction (Y) was determined at 7 T using in vitro bovine blood in a circulating system under physiological conditions. Blood (1)H2O R1 values for different conditions could be readily fitted using a two-compartment (erythrocyte and plasma) model, which are described by a monoexponential longitudinal relaxation rate constant dependence. It was found that T1 = 2171 ± 39 ms for Y = 1 (arterial blood) and 2010 ± 41 ms for Y = 0.6 (venous blood), for a typical Hct of 0.42. The blood (1)H2O T1 values in the normal physiological range (Hct from 0.35 to 0.45, and Y from 0.6 to 1.0) were determined to range from 1900 to 2300 ms. The influence of oxygen partial pressure (pO2) and the effect of plasma osmolality for different anticoagulants were also investigated. It is discussed why blood (1)H2O T1 values measured in vivo for human blood may be about 10-20% larger than found in vitro for bovine blood at the same field strength. PMID:23169066

  12. Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

    SciTech Connect

    Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S. )

    1990-11-01

    We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with (2-3H)glucose and HGP with (6-3H)glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). (2-3H)- minus (6-3H)glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

  13. Systemic responses of mice to dextran sulfate sodium-induced acute ulcerative colitis using 1H NMR spectroscopy.

    PubMed

    Dong, Fangcong; Zhang, Lulu; Hao, Fuhua; Tang, Huiru; Wang, Yulan

    2013-06-01

    The interplay between genetic mutation and environmental factors is believed to contribute to the etiology of inflammatory bowel disease (IBD). While focused attention has been paid to the aforementioned research, time-specific and organ-specific metabolic changes associated with IBD are still lacking. Here, we induced acute ulcerative colitis in mice by providing water containing 3% dextran sulfate sodium (DSS) for 7 days and investigated the metabolic changes of plasma, urine, and a range of biological tissues by employing a (1)H nuclear magnetic resonance (NMR)-based metabonomics approach with complementary information on serum clinical chemistry and histopathology. We found that DSS-induced acute ulcerative colitis leads to significant elevations in the levels of amino acids in plasma and decreased levels in the membrane-related metabolites and a range of nucleotides, nucleobases, and nucleosides in the colon. In addition, acute-colitis-induced elevations in the levels of nucleotides in the liver were observed, accompanied by reduced levels of glucose. DSS-induced acute colitis also resulted in increased levels of oxidized glutathione and attenuated levels of taurine in the spleen. Furthermore, acute colitis resulted in depletion in the levels of gut microbial cometabolites in urine along with an increase in citric acid cycle intermediates. These findings suggest that DSS-induced acute colitis causes a disturbance of lipid and energy metabolism, damage to the colon and liver, a promoted antioxidative and anti-inflammatory response, and perturbed gut microbiotal communities. The information obtained here provided details of the time-dependent and holistic metabolic changes in the development of the DSS-induced acute ulcerative colitis, which could be useful in discovery of novel therapeutic targets for management of IBD. PMID:23651354

  14. An Invert U-Shaped Curve: Relationship Between Fasting Plasma Glucose and Serum Uric Acid Concentration in a Large Health Check-Up Population in China

    PubMed Central

    Li, Haibo; Zha, Xiaojuan; Zhu, Yu; Liu, Mengxue; Guo, Rui; Wen, Yufeng

    2016-01-01

    Abstract There are some published studies focus on the invert U-shaped relationship between fasting plasma glucose (FPG) and serum uric acid (UA), while the threshold value and gender differences of this relationship were still obscure. We aimed to explore the dose–response relation between FPG level and serum UA concentration by conducted this epidemiological research in a large health check-up population in China. A total of 237,703 people were collected from January 2011 to July 2014 in our cross-sectional study; 100,348 subjects age 18 to 89 years and without known diabetes were included for the current analysis. One-way analysis of variance, generalized additive models, and 2-piecewise linear regression model were used. The mean concentration of UA with FPG of <6.1, 6.1 to 6.9, and ≥7.0 mmol/L was 240.9, 260.2, and 259.6 μmol/L in women and 349.0, 360.8, and 331.0 μmol/L in men. An invert U-shape with a threshold FPG of 7.5 (women)/6.5 (men) mmol/L was observed in the regression curve of FPG and UA, even after adjusting for potential confounders. The adjusted regression coefficients were 2.4 (95% confidence interval [CI]: 1.5 to 3.4, P < 0.001) for FPG < 7.5 mmol/L, −3.2 (95% CI: −5.0 to −1.3, P < 0.001) for FPG ≥ 7.5 mmol/L in women; while 0.8 (95% CI: −0.4 to 2.0, P = 0.19) for FPG < 6.5 mmol/L, −7.1 (95% CI: −8.0 to −6.1, P < 0.001) for FPG ≥ 6.5 mmol/L in men. Furthermore, the interaction between different FPG level and sex was significant (P < 0.05). An invert U-shape with a threshold of FPG was existed for serum UA level in Chinese adults age 18 to 89 years without known diabetes, and significant gender differences were found. Future researches should pay more attention to this relationship. PMID:27100447

  15. An Invert U-Shaped Curve: Relationship Between Fasting Plasma Glucose and Serum Uric Acid Concentration in a Large Health Check-Up Population in China.

    PubMed

    Li, Haibo; Zha, Xiaojuan; Zhu, Yu; Liu, Mengxue; Guo, Rui; Wen, Yufeng

    2016-04-01

    There are some published studies focus on the invert U-shaped relationship between fasting plasma glucose (FPG) and serum uric acid (UA), while the threshold value and gender differences of this relationship were still obscure. We aimed to explore the dose-response relation between FPG level and serum UA concentration by conducted this epidemiological research in a large health check-up population in China.A total of 237,703 people were collected from January 2011 to July 2014 in our cross-sectional study; 100,348 subjects age 18 to 89 years and without known diabetes were included for the current analysis. One-way analysis of variance, generalized additive models, and 2-piecewise linear regression model were used.The mean concentration of UA with FPG of <6.1, 6.1 to 6.9, and ≥7.0 mmol/L was 240.9, 260.2, and 259.6 μmol/L in women and 349.0, 360.8, and 331.0 μmol/L in men. An invert U-shape with a threshold FPG of 7.5 (women)/6.5 (men) mmol/L was observed in the regression curve of FPG and UA, even after adjusting for potential confounders. The adjusted regression coefficients were 2.4 (95% confidence interval [CI]: 1.5 to 3.4, P < 0.001) for FPG < 7.5 mmol/L, -3.2 (95% CI: -5.0 to -1.3, P < 0.001) for FPG ≥ 7.5 mmol/L in women; while 0.8 (95% CI: -0.4 to 2.0, P = 0.19) for FPG < 6.5 mmol/L, -7.1 (95% CI: -8.0 to -6.1, P < 0.001) for FPG ≥ 6.5 mmol/L in men. Furthermore, the interaction between different FPG level and sex was significant (P < 0.05).An invert U-shape with a threshold of FPG was existed for serum UA level in Chinese adults age 18 to 89 years without known diabetes, and significant gender differences were found. Future researches should pay more attention to this relationship. PMID:27100447

  16. Glucose control.

    PubMed

    Preiser, Jean-Charles

    2013-01-01

    Stress-related hyperglycemia is a common finding in acutely ill patients, and is related to the severity and outcome of the critical illness. The pathophysiology of stress hyperglycemia includes hormonal and neural signals, leading to increased production of glucose by the liver and peripheral insulin resistance mediated by the translocation of transmembrane glucose transporters. In one pioneering study, tight glycemic control by intensive insulin therapy in critically ill patients was associated with improved survival. However, this major finding was not confirmed in several other prospective randomized controlled trials. The reasons underlying the discrepancy between the first and the subsequent studies could include nutritional strategy (amount of calories provided, use of parenteral nutrition), case-mix, potential differences in the optimal blood glucose level (BG) in different types of patients, hypoglycemia and its correction, and the magnitude of glucose variability. Therefore, an improved understanding of the physiology and pathophysiology of glycemic regulation during acute illness is needed. Safe and effective glucose control will need improvement in the definition of optimal BG and in the measurement techniques, perhaps including continuous monitoring of insulin algorithms and closed-loop systems. PMID:23075589

  17. Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats

    PubMed Central

    Herring, Nicole R; Schaefer, Tori L; Tang, Peter H; Skelton, Matthew R; Lucot, James P; Gudelsky, Gary A; Vorhees, Charles V; Williams, Michael T

    2008-01-01

    Background Methamphetamine (MA) use is a worldwide problem. Abusers can have cognitive deficits, monoamine reductions, and altered magnetic resonance spectroscopy findings. Animal models have been used to investigate some of these effects, however many of these experiments have not examined the impact of MA on the stress response. For example, numerous studies have demonstrated (+)-MA-induced neurotoxicity and monoamine reductions, however the effects of MA on other markers that may play a role in neurotoxicity or cell energetics such as glucose, corticosterone, and/or creatine have received less attention. In this experiment, the effects of a neurotoxic regimen of (+)-MA (4 doses at 2 h intervals) on brain monoamines, neostriatal GFAP, plasma corticosterone, creatinine, and glucose, and brain and muscle creatine were evaluated 1, 7, 24, and 72 h after the first dose. In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session) 4 times at 2 h intervals]. Results MA increased corticosterone from 1–72 h with a peak 1 h after the first treatment, whereas glucose was only increased 1 h post-treatment. Neostriatal and hippocampal monoamines were decreased at 7, 24, and 72 h, with a concurrent increase in GFAP at 72 h. There was no effect of MA on regional brain creatine, however plasma creatinine was increased during the first 24 h and decreased by 72 h. As with MA treatment, forced swim increased corticosterone more than MA initially. Unlike MA, forced swim reduced creatine in the cerebellum with no change in other brain regions while plasma creatinine was decreased at 1 and 7 h. Glucose in plasma was decreased at 7 h. Conclusion Both MA and forced swim increase demand on energy substrates but in different ways, and MA has persistent effects on corticosterone that are not attributable to stress alone. PMID:18513404

  18. Postprandial glucose and insulin profiles following a glucose-loaded meal in cats and dogs.

    PubMed

    Hewson-Hughes, Adrian K; Gilham, Matthew S; Upton, Sarah; Colyer, Alison; Butterwick, Richard; Miller, Andrew T

    2011-10-01

    Data from intravenous (i.v.) glucose tolerance tests suggest that glucose clearance from the blood is slower in cats than in dogs. Since different physiological pathways are activated following oral administration compared with i.v. administration, we investigated the profiles of plasma glucose and insulin in cats and dogs following ingestion of a test meal with or without glucose. Adult male and female cats and dogs were fed either a high-protein (HP) test meal (15 g/kg body weight; ten cats and eleven dogs) or a HP + glucose test meal (13 g/kg body-weight HP diet + 2 g/kg body-weight D-glucose; seven cats and thirteen dogs) following a 24 h fast. Marked differences in plasma glucose and insulin profiles were observed in cats and dogs following ingestion of the glucose-loaded meal. In cats, mean plasma glucose concentration reached a peak at 120 min (10.2, 95 % CI 9.7, 10.8 mmol/l) and returned to baseline by 240 min, but no statistically significant change in plasma insulin concentration was observed. In dogs, mean plasma glucose concentration reached a peak at 60 min (6.3, 95 % CI 5.9, 6.7 mmol/l) and returned to baseline by 90 min, while plasma insulin concentration was significantly higher than pre-meal values from 30 to 120 min following the glucose-loaded meal. These results indicate that cats are not as efficient as dogs at rapidly decreasing high blood glucose levels and are consistent with a known metabolic adaptation of cats, namely a lack of glucokinase, which is important for both insulin secretion and glucose uptake from the blood. PMID:22005400

  19. The frog skin host-defense peptide CPF-SE1 improves glucose tolerance, insulin sensitivity and islet function and decreases plasma lipids in high-fat fed mice.

    PubMed

    Srinivasan, Dinesh; Ojo, Opeolu O; Owolabi, Bosede O; Conlon, J Michael; Flatt, Peter R; Abdel-Wahab, Yasser H A

    2015-10-01

    The frog skin host-defense peptide CPF-SE1 has previously been shown to stimulate the in vitro release of insulin from clonal BRIN-BD11 β-cells. In this study, the in vivo effects of the peptide were investigated in male NIH Swiss mice maintained on a high-fat diet to induce obesity and insulin resistance. Insulin-secretory responses of islets isolated from treated and untreated mice and changes in islet morphology were also examined. Total body fat, plasma glucagon, triglyceride and cholesterol concentrations were measured at the end of the treatment period. Acute intraperitoneal administration of CPF-SE1 (75 nmol body weight) to high-fat fed mice together with glucose (18 mmol/kg body weight) improved glucose tolerance and insulin responses compared to high-fat fed controls. Long term administration of CPF-SE1 (twice-daily administration of 75 nmol/kg body weight for 28 days) did not affect body weight or energy intake but decreased circulating glucose and increased insulin concentrations. Insulin sensitivity and insulin-secretory responses of islets to secretagogues were also significantly improved at 28 days in peptide-treated mice. In addition, significant decreases in plasma glucagon concentrations, pancreatic insulin and glucagon content, islet and beta cell area, body fat and plasma triglyceride levels were observed in CPF-SE1 treated with mice. In conclusion, CPF-SE1 improves beta cell function, insulin sensitivity and glycaemic control whilst reducing total body fat and circulating triglyceride levels. The peptide shows potential for development into an agent for treatment of patients with metabolic syndrome and type 2 diabetes. PMID:26123844

  20. Glucose Variability

    PubMed Central

    2013-01-01

    The proposed contribution of glucose variability to the development of the complications of diabetes beyond that of glycemic exposure is supported by reports that oxidative stress, the putative mediator of such complications, is greater for intermittent as opposed to sustained hyperglycemia. Variability of glycemia in ambulatory conditions defined as the deviation from steady state is a phenomenon of normal physiology. Comprehensive recording of glycemia is required for the generation of any measurement of glucose variability. To avoid distortion of variability to that of glycemic exposure, its calculation should be devoid of a time component. PMID:23613565

  1. 1H NMR spectra part 31: 1H chemical shifts of amides in DMSO solvent.

    PubMed

    Abraham, Raymond J; Griffiths, Lee; Perez, Manuel

    2014-07-01

    The (1)H chemical shifts of 48 amides in DMSO solvent are assigned and presented. The solvent shifts Δδ (DMSO-CDCl3 ) are large (1-2 ppm) for the NH protons but smaller and negative (-0.1 to -0.2 ppm) for close range protons. A selection of the observed solvent shifts is compared with calculated shifts from the present model and from GIAO calculations. Those for the NH protons agree with both calculations, but other solvent shifts such as Δδ(CHO) are not well reproduced by the GIAO calculations. The (1)H chemical shifts of the amides in DMSO were analysed using a functional approach for near ( ≤ 3 bonds removed) protons and the electric field, magnetic anisotropy and steric effect of the amide group for more distant protons. The chemical shifts of the NH protons of acetanilide and benzamide vary linearly with the π density on the αN and βC atoms, respectively. The C=O anisotropy and steric effect are in general little changed from the values in CDCl3. The effects of substituents F, Cl, Me on the NH proton shifts are reproduced. The electric field coefficient for the protons in DMSO is 90% of that in CDCl3. There is no steric effect of the C=O oxygen on the NH proton in an NH…O=C hydrogen bond. The observed deshielding is due to the electric field effect. The calculated chemical shifts agree well with the observed shifts (RMS error of 0.106 ppm for the data set of 257 entries). PMID:24824670

  2. Rapid and specific isolation of radioactive glucose from biological samples.

    PubMed

    Mills, S E; Armentano, L E; Russell, R W; Young, J W

    1981-08-01

    An easy, reliable, and specific ion-exchange method is presented for isolating glucose for specific radioactivity determinations from both blood plasma and buffered in vitro incubation media. The use of a glucose binding resin (borate-charged anion resin) combined speed of ion exchange with specificity of derivative formation. Glucose specific radioactivities, determined by ion exchange on protein-free filtrates of plasma containing [carbon-14] glucose, show excellent agreement with those from the popular glucose pentaacetate derivative method and are less variable. Carry-over of labeled acetate, propionate, lactate, glyoxylate, alanine, aspartate, or glutamate into the glucose fraction is less than .2%. Glycerol carryover is 1.2%. Glucose recovery is increased about three times that of the glucose pentaacetate derivative method and averaged 94% from plasma filtrates. PMID:7298970

  3. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial

    PubMed Central

    Liu, Yuejun; Cotillard, Aurélie; Vatier, Camille; Bastard, Jean-Philippe; Fellahi, Soraya; Stévant, Marie; Allatif, Omran; Langlois, Clotilde; Bieuvelet, Séverine; Brochot, Amandine; Guilbot, Angèle; Clément, Karine; Rizkalla, Salwa W.

    2015-01-01

    Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. Methods In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Results Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Conclusions Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. Trial Registration ClinicalTrials.gov NCT01530685 PMID:26406981

  4. Impact of diabetes duration on achieved reductions in glycated haemoglobin, fasting plasma glucose and body weight with liraglutide treatment for up to 28 weeks: a meta-analysis of seven phase III trials.

    PubMed

    Seufert, J; Bailey, T; Barkholt Christensen, S; Nauck, M A

    2016-07-01

    This meta-analysis of seven randomized, placebo-controlled studies (total 3222 patients) evaluated whether type 2 diabetes (T2D) duration affects the changes in blood glucose control and body weight that can be achieved with liraglutide and placebo. With liraglutide 1.2 mg, shorter diabetes duration was associated with a significantly greater, but clinically non-relevant, difference in glycated haemoglobin (HbA1c) reduction (p < 0.05), i.e. a 0.18% (1.96 mmol/mol) reduction in HbA1c per 10 years shorter diabetes duration. With liraglutide 1.8 mg, shorter diabetes duration was associated with a small but statistically significant trend for greater fasting plasma glucose (FPG) reduction (p < 0.05), i.e. a 0.38 mmol/l reduction in FPG per 10 years shorter diabetes duration. Neither the liraglutide 1.8 mg nor placebo results showed a significant association between HbA1c and diabetes duration and neither the liraglutide 1.2 mg nor placebo results showed a significant association between FPG and diabetes duration. Likewise, neither liraglutide nor placebo showed a significant association between change in weight and diabetes duration. These results suggest diabetes duration has a clinically negligible effect on achievable blood glucose control and weight outcomes with liraglutide and placebo in patients with T2D. PMID:26679282

  5. Estimation of liver glucose metabolism after refeeding

    SciTech Connect

    Rognstad, R.

    1987-05-01

    Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a /sup 14/C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the /sup 14/C yield from H/sup 14/CO/sub 3//sup -/ in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding.

  6. A UPLC-MS/MS method for simultaneous determination of danshensu, protocatechuic aldehyde, rosmarinic acid, and ligustrazine in rat plasma, and its application to pharmacokinetic studies of Shenxiong glucose injection in rats.

    PubMed

    Zheng, Lin; Gong, Zipeng; Lu, Yuan; Xie, Yumin; Huang, Yong; Liu, Yue; Lan, Yanyu; Wang, Aimin; Wang, Yonglin

    2015-08-01

    A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of the four major active ingredients, danshensu, protocatechuic aldehyde, rosmarinic acid, and ligustrazine, in the traditional Chinese medicine Shenxiong glucose injection in rat plasma. Acidified and alkalized plasma samples were extracted using ethyl acetate, and separated on a Waters C18 column (2.1mm×50mm, 1.7μm) by using a gradient mobile phase system of acetonitrile-water containing 0.1% formic acid and luteoloside as an internal standard. Electrospray ionization in the positive-ion mode and multiple reaction monitoring were used to identify and quantitate the active components. All calibration curves showed good linearity (r>0.994) over the concentration range, with a lower limit of quantification (LLOQ) between 0.02 and 0.21μg/mL. The precision of the in vivo study was evaluated by intra- and inter-day assays, and the percentage of relative standard deviation was within 15%. Moreover, satisfactory extraction efficiency was obtained (between 83.94 and 117.81%) by liquid-liquid extraction. The validated method was successfully applied in a pharmacokinetic study in rats after intravenous administration of Shenxiong glucose injection. The results showed that the four bioactive ingredients in Shenxiong glucose injection have linear pharmacokinetic properties in rats after intravenous injection within the administered dose range and partially different ones compared to single ingredient. PMID:26118621

  7. An improved technique for the 2H/1H analysis of urines from diabetic volunteers

    USGS Publications Warehouse

    Coplen, T.B.; Harper, I.T.

    1994-01-01

    The H2-H2O ambient-temperature equilibration technique for the determination of 2H/1H ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, ~ 1-2???, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique.The H2-H2O ambient-temperature equilibration technique for the determination of 2H/1H ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, approximately 1-2%, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique.

  8. (1)H NMR Spectroscopy of Fecal Extracts Enables Detection of Advanced Colorectal Neoplasia.

    PubMed

    Amiot, Aurelien; Dona, Anthony C; Wijeyesekera, Anisha; Tournigand, Christophe; Baumgaertner, Isabelle; Lebaleur, Yann; Sobhani, Iradj; Holmes, Elaine

    2015-09-01

    Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its etiopathogenesis and earlier diagnosis. Here, we investigated the fecal metabolic phenotype of patients with advanced colorectal neoplasia and controls using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate modeling. The fecal microbiota composition was assessed by quantitative real-time PCR as well as Wif-1 methylation levels in stools, serum, and urine and correlated to the metabolic profile of each patient. The predictivity of the model was 0.507 (Q(2)Y), and the explained variance was 0.755 (R(2)Y). Patients with advanced colorectal neoplasia demonstrated increased fecal concentrations of four short-chain fatty acids (valerate, acetate, propionate, and butyrate) and decreased signals relating to β-glucose, glutamine, and glutamate. The predictive accuracy of the multivariate (1)H NMR model was higher than that of the guaiac-fecal occult blood test and the Wif-1 methylation test for predicting advanced colorectal neoplasia. Correlation analysis between fecal metabolites and bacterial profiles revealed strong associations between Faecalibacterium prausnitzii and Clostridium leptum species with short-chain fatty acids concentration and inverse correlation between Faecalibacterium prausnitzii and glucose. These preliminary results suggest that fecal metabonomics may potentially have a future role in a noninvasive colorectal screening program and may contribute to our understanding of the role of these dysregulated molecules in the cross-talk between the host and its bacterial microbiota. PMID:26211820

  9. Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

    SciTech Connect

    Altszuler, N.; Puma, F.; Winkler, B.; Fontan, N.; Saudek, C.D.

    1986-05-01

    Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin of 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the (6-/sup 3/H)glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 ..mu..U/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. it is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production.

  10. Effects of six carbohydrate sources on diet digestibility and postprandial glucose and insulin responses in cats.

    PubMed

    de-Oliveira, L D; Carciofi, A C; Oliveira, M C C; Vasconcellos, R S; Bazolli, R S; Pereira, G T; Prada, F

    2008-09-01

    The effects of diets with different starch sources on the total tract apparent digestibility and glucose and insulin responses in cats were investigated. Six experimental diets consisting of 35% starch were extruded, each containing one of the following ingredients: cassava flour, brewers rice, corn, sorghum, peas, or lentils. The experiment was carried out on 36 cats with 6 replications per diet in a completely randomized block design. The brewers rice diet offered greater DM, OM, and GE digestibility than the sorghum, corn, lentil, and pea diets (P < 0.05). For starch digestibility, the brewers rice diet had greater values (98.6%) than the sorghum (93.9%), lentil (95.2%), and pea (96.3%) diets (P < 0.05); however, starch digestibility was >93% for all the diets, proving that despite the low carbohydrate content of carnivorous diets, cats can efficiently digest this nutrient when it is properly processed into kibble. Mean and maximum glucose concentration and area under the glucose curve were greater for the corn-based diet than the cassava flour, sorghum, lentil, and pea diets (P < 0.05). The corn-based diets led to greater values for the mean glucose incremental concentration (10.2 mg/dL), maximum glucose incremental concentration (24.8 mg/dL), and area under the incremental glucose curve (185.5 mg.dL(-1).h(-1)) than the lentil diet (2.9 mg/dL, 3.1 mg/dL, and -40.4 mg.dL(-1).h(-1), respectively; P < 0.05). When compared with baseline values, only the corn diet stimulated an increase in the glucose response, occurring at 4 and 10 h postmeal (P < 0.05). The corn-based diet resulted in greater values for maximum incremental insulin concentration and area under the incremental insulin curve than the lentil-based diet (P < 0.05). However, plasma insulin concentrations rose in relation to the basal values for cats fed corn, sorghum, pea, and brewers rice diets (P < 0.05). Variations in diet digestibility and postprandial response can be explained by differences in the

  11. 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.

  12. Noninvasive glucose sensing by transcutaneous Raman spectroscopy

    PubMed Central

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

    2015-01-01

    Abstract. 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. PMID:25688542

  13. Identifying metabolites related to nitrogen mineralisation using 1H NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    . T McDonald, Noeleen; Graham, Stewart; Watson, Catherine; Gordon, Alan; Lalor, Stan; Laughlin, Ronnie; Elliott, Chris; . P Wall, David

    2015-04-01

    Exploring new analysis techniques to enhance our knowledge of the various metabolites within our soil systems is imperative. Principally, this knowledge would allow us to link key metabolites with functional influences on critical nutrient processes, such as the nitrogen (N) mineralisation in soils. Currently there are few studies that utilize proton nuclear magnetic resonance spectroscopy (1H NMR) to characterize multiple metabolites within a soil sample. The aim of this research study was to examine the effectiveness of 1H NMR for isolating multiple metabolites that are related to the mineralizable N (MN) capacity across a range of 35 Irish grassland soils. Soils were measured for MN using the standard seven day anaerobic incubation (AI-7). Additionally, soils were also analysed for a range of physio-chemical properties [e.g. total N, total C, mineral N, texture and soil organic matter (SOM)]. Proton NMR analysis was carried on these soils by extracting with 40% methanol:water, lyophilizing and reconstituting in deuterium oxide and recording the NMR spectra on a 400MHz Bruker AVANCE III spectrometer. Once the NMR data were spectrally processed and analysed using multivariate statistical analysis, seven metabolites were identified as having significant relationships with MN (glucose, trimethylamine, glutamic acid, serine, aspartic acid, 4-aminohippuirc acid and citric acid). Following quantification, glucose was shown to explain the largest percentage variability in MN (72%). These outcomes suggest that sources of labile carbon are essential in regulating N mineralisation and the capacity of plant available N derived from SOM-N pools in these soils. Although, smaller in concentration, the amino acids; 4-aminohippuirc acid, glutamic acid and serine also significantly (P<0.05) explained 43%, 27% and 19% of the variability in MN, respectively. This novel study highlights the effectiveness of using 1H NMR as a practical approach to profile multiple metabolites in

  14. AMPK-Regulated and Akt-Dependent Enhancement of Glucose Uptake Is Essential in Ischemic Preconditioning-Alleviated Reperfusion Injury

    PubMed Central

    Liu, Wenchong; Huang, Qichao; Yang, Weidong; Fu, Feng; Ma, Heng; Su, Hui; Wang, Haichang; Wang, Jing; Zhang, Haifeng; Gao, Feng

    2013-01-01

    Aims Ischemic preconditioning (IPC) is a potent form of endogenous protection. However, IPC-induced cardioprotective effect is significantly blunted in insulin resistance-related diseases and the underlying mechanism is unclear. This study aimed to determine the role of glucose metabolism in IPC-reduced reperfusion injury. Methods Normal or streptozotocin (STZ)-treated diabetic rats subjected to 2 cycles of 5 min ischemia/5 min reperfusion prior to myocardial ischemia (30 min)/reperfusion (3 h). Myocardial glucose uptake was determined by 18F-fluorodeoxyglucose-positron emission tomography (PET) scan and gamma-counter biodistribution assay. Results IPC exerted significant cardioprotection and markedly improved myocardial glucose uptake 1 h after reperfusion (P<0.01) as evidenced by PET images and gamma-counter biodistribution assay in ischemia/reperfused rats. Meanwhile, myocardial translocation of glucose transporter 4 (GLUT4) to plasma membrane together with myocardial Akt and AMPK phosphorylation were significantly enhanced in preconditioned hearts. Intramyocardial injection of GLUT4 siRNA markedly decreased GLUT4 expression and blocked the cardioprotection of IPC as evidence by increased myocardial infarct size. Moreover, the PI3K inhibitor wortmannin significantly inhibited activation of Akt and AMPK, reduced GLUT4 translocation, glucose uptake and ultimately, depressed IPC-induced cardioprotection. Furthermore, IPC-afforded antiapoptotic effect was markedly blunted in STZ-treated diabetic rats. Exogenous insulin supplementation significantly improved glucose uptake via co-activation of myocardial AMPK and Akt and alleviated ischemia/reperfusion injury as evidenced by reduced myocardial apoptosis and infarction size in STZ-treated rats (P<0.05). Conclusions The present study firstly examined the role of myocardial glucose metabolism during reperfusion in IPC using direct genetic modulation in vivo. Augmented glucose uptake via co-activation of myocardial AMPK

  15. Serum metabolic signature of minimal hepatic encephalopathy by (1)H-nuclear magnetic resonance.

    PubMed

    Jiménez, Beatriz; Montoliu, Carmina; MacIntyre, David A; Serra, Miguel A; Wassel, Abdallah; Jover, María; Romero-Gomez, Manuel; Rodrigo, Jose M; Pineda-Lucena, Antonio; Felipo, Vicente

    2010-10-01

    Minimal hepatic encephalopathy (MHE) reduces quality of life of cirrhotic patients, predicts overt hepatic encephalopathy, and is associated with poor prognosis. We hypothesized that MHE arises once metabolic alterations derived from the liver reach a particular threshold. Our aim was to assess whether metabolic profiling of serum samples by high-field (1)H-nuclear magnetic resonance spectroscopy ((1)H NMR) and subsequent multivariate analyses would be useful to characterize metabolic perturbations associated with MHE and to identify potential metabolic biomarkers. Metabolic serum profiles from controls (n = 69) and cirrhotic patients without MHE (n = 62) and with MHE (n = 39) were acquired using high field NMR. Supervised modeling of the data provided perfect discrimination between healthy controls and cirrhotic patients and allowed the generation of a predictive model displaying strong discrimination between patients with and without MHE (R(2)Y = 0.68, Q(2)Y = 0.63). MHE patients displayed increased serum concentrations of glucose, lactate, methionine, TMAO, and glycerol, as well as decreased levels of choline, branch amino acids, alanine, glycine, acetoacetate, NAC, and lipid moieties. Serum metabonomics by (1)H NMR offers a useful approach for characterizing underlying metabolic differences between patients with and without MHE. This procedure shows great potential as a diagnostic tool of MHE as it objectively reflects measurable biochemical differences between the patient groups and may facilitate monitoring of both disease progression and effects of therapeutic treatments. PMID:20690770

  16. Cross Polarization for 1H NMR Image Contrast in Solids

    NASA Astrophysics Data System (ADS)

    Nakai, Toshihito; Fukunaga, Yasuhiro; Nonaka, Masayuki; Matsui, Shigeru; Inouye, Tamon

    1998-09-01

    A novel1H imaging method for solids, yielding images reflecting1H-13C dipolar interactions through cross relaxation timeTIS, is presented. Phase-alternating multiple-contact cross polarization (PAMC CP) was incorporated into the magic-echo frequency-encoding imaging scheme; the PAMC CP sequence may partly but efficiently destroy the initial1H magnetization depending on theTISvalues. A theory describing the effects of the PAMC CP sequence was developed, which was used for the assessment of the sequence as well as the analysis for the experimental results. It was demonstrated that theTIS-weighted1H image and theTISmapping for a phantom, constituted of adamantane and ferrocene, can distinguish these compounds clearly.

  17. Glucose kinetics during prolonged exercise in highly trained human subjects: effect of glucose ingestion

    PubMed Central

    Jeukendrup, Asker E; Raben, Anne; Gijsen, Annemie; Stegen, Jos H C H; Brouns, Fred; Saris, Wim H M; Wagenmakers, Anton J M

    1999-01-01

    The objectives of this study were (1) to investigate whether glucose ingestion during prolonged exercise reduces whole body muscle glycogen oxidation, (2) to determine the extent to which glucose disappearing from the plasma is oxidized during exercise with and without carbohydrate ingestion and (3) to obtain an estimate of gluconeogenesis. After an overnight fast, six well-trained cyclists exercised on three occasions for 120 min on a bicycle ergometer at 50% maximum velocity of O2 uptake and ingested either water (Fast), or a 4% glucose solution (Lo-Glu) or a 22% glucose solution (Hi-Glu) during exercise. Dual tracer infusion of [U-13C]-glucose and [6,6-2H2]-glucose was given to measure the rate of appearance (Ra) of glucose, muscle glycogen oxidation, glucose carbon recycling, metabolic clearance rate (MCR) and non-oxidative disposal of glucose. Glucose ingestion markedly increased total Ra especially with Hi-Glu. After 120 min Ra and rate of disappearance (Rd) of glucose were 51-52 μmol kg−1 min−1 during Fast, 73-74 μmol kg−1 min−1 during Lo-Glu and 117–119 μmol kg−1 min−1 during Hi-Glu. The percentage of Rd oxidized was between 96 and 100% in all trials. Glycogen oxidation during exercise was not reduced by glucose ingestion. The vast majority of glucose disappearing from the plasma is oxidized and MCR increased markedly with glucose ingestion. Glucose carbon recycling was minimal suggesting that gluconeogenesis in these conditions is negligible. PMID:10050023

  18. The influence of nutrition on the insulin-like growth factor system and the concentrations of growth hormone, glucose, insulin, gonadotropins and progesterone in ovarian follicular fluid and plasma from adult female horses (Equus caballus)

    PubMed Central

    2014-01-01

    Background Feed intake affects the GH-IGF system and may be a key factor in determining the ovarian follicular growth rate. In fat mares, the plasma IGF-1 concentration is high with low GH and a quick follicular growth rate, in contrast to values observed in thin mares. Nothing is known regarding the long-term effects of differential feed intake on the IGF system. The objective of this experiment was to quantify IGFs, IGFBPs, GH, glucose, insulin, gonadotropin and progesterone (P4) in blood and in preovulatory follicular fluid (FF) in relation to feeding levels in mares. Methods Three years prior to the experiment, Welsh Pony mares were assigned to a restricted diet group (R, n = 10) or a well-fed group (WF, n = 9). All mares were in good health and exhibited differences in body weight and subcutaneous fat thickness. Follicular development was scanned daily and plasma was also collected daily. Preovulatory FF was collected by ultrasound-guided follicular aspiration. Hormone levels were assayed in FF and plasma with a validated RIA. Results According to scans, the total number of follicles in group R was 53% lower than group WF. Insulin and IGF-1 concentrations were higher in WF than in R mares. GH and IGF-2 concentrations were lower in plasma from WF mares than from R mares, but the difference was not significant in FF. The IGFBP-2/IGFBP-3 ratio in FF was not affected by feeding but was dramatically increased in R mare plasma. No difference in gonadotropin concentration was found with the exception of FSH, which was higher in the plasma of R mares. On the day of puncture, P4 concentrations were not affected by feeding but were higher in preovulatory FF than in plasma. Conclusions The bioavailability of IGF-1 or IGF-2, represented by the IGFBP2/IGFBP3 ratio, is modified by feed intake in plasma but not in FF. These differences partially explain the variability in follicular growth observed between well-fed mares and mares on restricted diets. PMID:25078409

  19. Regulation of Arabidopsis thaliana plasma membrane glucose-responsive regulator (AtPGR) expression by A. thaliana storekeeper-like transcription factor, AtSTKL, modulates glucose response in Arabidopsis.

    PubMed

    Chung, Moon-Soo; Lee, Sungbeom; Min, Ji-Hee; Huang, Ping; Ju, Hyun-Woo; Kim, Cheol Soo

    2016-07-01

    Biochemical, genetic, physiological, and molecular research in plants has demonstrated a central role of glucose (Glc) in the control of plant growth, metabolism, and development, and has revealed networks that integrate light, stresses, nutrients, and hormone signaling. Previous studies have reported that AtPGR protein as potential candidates for Glc signaling protein. In the present study, we characterized transcription factors that bind to the upstream region of the AtPGR gene isolated using the yeast one-hybrid screening with an Arabidopsis cDNA library. One of the selected genes (AtSTKL) appeared to confer elevated sensitivity to Glc response. Overexpression of AtSTKLs (AtSTKL1 and AtSTKL2) increased the sensitivity to Glc during the post-germination stages. In contrast, atstkl1 and atstkl2 antisense lines displayed reduced sensitivity to high Glc concentration during the early seedling stage. Furthermore, we showed that the two AtSTKLs bind to the 5'-GCCT-3' element of the upstream promoter region of the AtPGR gene in vitro and repress the beta-glucuronidase (GUS) activity in AtPGR promoter-GUS (P999-GUS) transgenic plants. Green fluorescent protein (GFP)-tagged AtSTKLs were localized in the nuclei of transgenic Arabidopsis cells. Collectively, these results suggest that AtSTKL1 and AtSTKL2 function both as repressors of AtPGR transcription and as novel transcription factors in the Glc signaling pathway. PMID:27031427

  20. Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin.

    PubMed

    Wolf-Novak, L C; Stegink, L D; Brummel, M C; Persoon, T J; Filer, L J; Bell, E F; Ziegler, E E; Krause, W L

    1990-04-01

    Seven subjects homozygous for phenylketonuria (PKU) and seven normal subjects were administered four beverage regimens after an overnight fast: unsweetened beverage, beverage providing carbohydrate (CHO), beverage providing aspartame (APM), and beverage providing APM plus CHO. The APM dose (200 mg) was the amount provided in 12 oz of diet beverage; the CHO was partially hydrolyzed starch (60 g). Plasma amino acid concentrations were determined after dosing and the molar plasma phenylalanine (Phe) to large neutral amino acid (LNAA) ratio calculated. APM administration without CHO did not increase plasma Phe concentrations over baseline values in either normal or PKU subjects (5.48 +/- 0.85 and 150 +/- 23.0 mumols/dL, respectively). Similarly, the Phe/LNAA did not increase significantly. Ingestion of beverage providing APM and CHO did not significantly increase plasma Phe concentrations over baseline values in either normal or PKU subjects. However, ingestion of beverage providing CHO (with or without APM) significantly decreased plasma levels of valine, isoleucine, and leucine 1.5 to 4 hours after dosing in both normal and PKU subjects, thereby increasing the Phe/LNAA ratio significantly. These data indicate that changes noted in Phe/LNAA values after ingestion of beverage providing APM plus CHO were due to CHO. The plasma insulin response to beverage providing CHO (with or without APM) was significantly higher in PKU subjects than in normals. PMID:2182973

  1. Intrapulmonary administration of natural honey solution, hyperosmolar dextrose or hypoosmolar distill water to normal individuals and to patients with type-2 diabetes mellitus or hypertension: their effects on blood glucose level, plasma insulin and C-peptide, blood pressure and peaked expiratory flow rate.

    PubMed

    Al-Waili, N

    2003-07-31

    Safety and effect intrapulmonary administration (by inhalation) of 60 % honey solution, 10% dextrose or distill water on blood sugar, plasma insulin and C-peptide, blood pressure, heart rate, and peaked expiratory flow rate (PEFR) in normal or diabetic subjects were studied. - Twenty-four healthy subjects, 16 patients with type 11 diabetes mellitus and six patients with hypertension were entered for study. They were underwent complete physical examination and laboratory investigations. Twelve healthy subjects were subjected for distill water inhalation for 10 min, and after one week they received inhalation of honey solution (60% wt/v) for 10 min. Another 12 healthy subjects received inhalation of 10% dextrose for 10 min. Blood glucose level, plasma insulin and C-peptide, blood pressure, heart rate and PEFR were estimated before inhalation and during 2-3 hrs after inhalation, at 30 min intervals. Random blood glucose level was estimated in eight patients with poorly controlled diabetes mellitus, and repeated 30 min after honey inhalation. One week later, fasting blood glucose level was estimated in each patient and blood glucose level was re-estimated during three hrs after honey inhalation, at 30 min intervals. Glucose tolerance test was performed in another eight patients with type-2 diabetes mellitus, and after one week the procedure was repeated with inhalation of honey, which was started immediately after ingestion of glucose. Six hypertensive patients received honey inhalation for 10 min; supine blood pressure and heart rate were measured before and after inhalation. - Results showed that in normal subjects distill water caused mild elevation of blood glucose level, mild lowering of plasma insulin, and significant reduction of plasma C-peptide. 10% dextrose inhalation caused mild reduction of plasma insulin and C-peptide and unremarkable changes in blood glucose level. No significant changes were obtained in blood pressure, heart rate or PEFR after distill

  2. What is a normal blood glucose?

    PubMed

    Güemes, Maria; Rahman, Sofia A; Hussain, Khalid

    2016-06-01

    Glucose is the key metabolic substrate for tissue energy production. In the perinatal period the mother supplies glucose to the fetus and for most of the gestational period the normal lower limit of fetal glucose concentration is around 3 mmol/L. Just after birth, for the first few hours of life in a normal term neonate appropriate for gestational age, blood glucose levels can range between 1.4 mmol/L and 6.2 mmol/L but by about 72 h of age fasting blood glucose levels reach normal infant, child and adult values (3.5-5.5 mmol/L). Normal blood glucose levels are maintained within this narrow range by factors which control glucose production and glucose utilisation. The key hormones which regulate glucose homoeostasis include insulin, glucagon, epinephrine, norepinephrine, cortisol and growth hormone. Pathological states that affect either glucose production or utilisation will lead to hypoglycaemia. Although hypoglycaemia is a common biochemical finding in children (especially in the newborn) it is not possible to define by a single (or a range of) blood glucose value/s. It can be defined as the concentration of glucose in the blood or plasma at which the individual demonstrates a unique response to the abnormal milieu caused by the inadequate delivery of glucose to a target organ (eg, the brain). Hypoglycaemia should therefore be considered as a continuum and the blood glucose level should be interpreted within the clinical scenario and with respect to the counter-regulatory hormonal responses and intermediate metabolites. PMID:26369574

  3. Glucose test (image)

    MedlinePlus

    ... person with diabetes constantly manages their blood's sugar (glucose) levels. After a blood sample is taken and tested, it is determined whether the glucose levels are low or high. If glucose levels ...

  4. Low Blood Glucose (Hypoglycemia)

    MedlinePlus

    ... Other Dental Problems Diabetic Eye Disease Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low ... actions can also help prevent hypoglycemia: Check blood glucose levels Knowing your blood glucose level can help ...

  5. High resolution 1H solid state NMR studies of polyethyleneterephthalate

    NASA Astrophysics Data System (ADS)

    Cheung, T. T. P.; Gerstein, B. C.; Ryan, L. M.; Taylor, R. E.; Dybowski, D. R.

    1980-12-01

    Molecular motions and spatial properties of the solid polymer polyethyleneterephthalate have been investigated using high resolution 1H solid state NMR techniques. The longitudinal spin relaxation time T1ρ of protons (1H) in the rotating frame was measured for a spin locking field ranging from 5 to 20 G. The decay of the 1H magnetization indicated the existence of two distinct T1ρ's and their field dependence shows that they are associated with two mobile phases of the polymer. The 1H magnetization also relaxes under the dipolar narrowed Carr-Purcell (DNCP) multipulse sequence with two dintinct T1y relaxation times. The ratios T1y's and T1ρ's deviate significantly from the expected theoretical values. The combined experiment with magic angle spinning and the DNCP sequence followed by homonuclear dipolar decoupling reveals the individual T1y relaxation of the resolved methylene and aromatic protons. These two species of protons were found to relax with the same T1y's, thus implying that spin diffusion must have taken place under the homonuclear dipolar decoupling multipulse. The qualitative description of spin diffusion under homonuclear decoupling is given. The combined experiment with spin locking and the DNCP sequence yields the correspondence between the two T1ρ's and the two T1y's. The long T1ρ corresponds to the short T1y whereas the short T1ρ corresponds to the long T1y. Communication between the two spatial phases via spin diffusion was also observed in this experiment by monitoring the recovery of the 1H magnitization associated with the short T1ρ after it has been eliminated during the spin locking. The total 1H magnetization is allowed to equilibrate in the laboratory frame for a variable time much shorter than T1 after the spin locking field has been turned off. The spatial relationship between the two phases is discussed.

  6. Localized double-quantum-filtered 1H NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Thomas, M. A.; Hetherington, H. P.; Meyerhoff, D. J.; Twieg, D. B.

    The image-guided in vivo spectroscopic (ISIS) pulse sequence has been combined with a double-quantum-filter scheme in order to obtain localized and water-suppressed 1H NMR spectra of J-coupled metabolites. The coherence-transfer efficiency associated with the DQ filter for AX and A 3X spin systems is described. Phantom results of carnosine, alanine, and ethanol in aqueous solution are presented. For comparison, the 1H NMR spectrum of alanine in aqueous solution with the binomial (1331, 2662) spin-echo sequence is also shown.

  7. A Common Missense Variant in the Glucokinase Regulatory Protein Gene (GCKR) Is Associated with Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE-Using the genome-wide-association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metaboli...

  8. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

    PubMed Central

    Gooda Sahib Jambocus, Najla; Saari, Nazamid; Ismail, Amin; Mahomoodally, Mohamad Fawzi; Abdul Hamid, Azizah

    2016-01-01

    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a 1H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment. PMID:26798649

  9. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a (1)H NMR Metabolomics Approach.

    PubMed

    Gooda Sahib Jambocus, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Mohamad Fawzi; Abdul Hamid, Azizah

    2016-01-01

    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment. PMID:26798649

  10. Dietary effects in the early recovery phase of kwashiorkor. Plasma levels of triglycerides, FFA, D-beta-hydroxybutyrate, glycerol, postheparin lipoprotein lipase (LPL), glucose and insulin.

    PubMed

    Persson, B; Habte, D; Sterky, G

    1976-05-01

    The fatty liver often found in untreated kwashiorkor has been associated with highly variable concentration of circulating lipids. The effect on lipid metabolism of two isocaloric diets--one synthetic monomolecular (Vivonex) and one standard (Casilan)--which both initiated satisfactory clinical improvement was studied in 21 Ethiopian children with kwashiorkor during the first weeks of rehabilitation. Before treatment mean fasting values of all biochemical parameters were within normal ranges except for moderately elevated triglycerides--an unexpected finding-and low insulin. Individual values varied greatly; triglyceride between 0.39 and 3.49 mmol/1. FFA correlated both to glycerol, D-beta-hydroxybutyrate and triglyceride values. During treatment insulin, glucose and glycerol remained essentially unchanged and were similar in both dietary groups. In the Vivonex group only there was an initial marked, parallel fall of FFA and D-beta-hydroxybutyrate suggesting greater availability of carbohydrate and enhanced glucose utilization. This pattern of response seemed to occur without comparable inhibition of lipolysis. Triglycerides--like serum albumin--increased faster in the Casilan group. The highest mean triglyceride value was reached by day 8 in the Casilan group and by day 15 in the Vivonex group. Ten minutes following heparin injection triglycerides declined, FFA and glycerol increased indicating release of in vivo active lipase. LPL activity assayed in vitro was similar and unaffected by 2 weeks of dietary treatment in both groups. LPL activity was inversely correlated to triglycerides providing--beside the type of diet--another possible explanation for the wide variations seen in circulatory triglycerides. PMID:1274567

  11. 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

  12. Applications of 1H-NMR to Biodiesel Research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biodiesel is an alternative diesel fuel derived from vegetable oils, animal fats, or used cooking oils. It is produced by reacting these materials with an alcohol in the presence of a catalyst to give the corresponding mono-alkyl esters. 1H-NMR is a routine analytical method that has been used for...

  13. Effects of alpha and beta adrenergic blockade on hepatic glucose balance before and after oral glucose. Role of insulin and glucagon.

    PubMed Central

    Chap, Z; Ishida, T; Chou, J; Michael, L; Hartley, C; Entman, M; Field, J B

    1986-01-01

    In conscious dogs, phentolamine infusion significantly increased fasting portal vein insulin, glucagon, and decreased net hepatic glucose output and plasma glucose. Propranolol significantly decreased portal vein insulin, portal flow, and increased hepatic glucose production and plasma glucose. Phentolamine, propranolol, and combined blockade reduced glucose absorption after oral glucose. alpha, beta, and combined blockade abolished the augmented fractional hepatic insulin extraction after oral glucose. Despite different absolute amounts of glucose absorbed and different amounts of insulin reaching the liver, the percent of the absorbed glucose retained by the liver was similar for control and with alpha- or beta blockade, but markedly decreased with combined blockade. Our conclusions are: (a) phentolamine and propranolol effects on basal hepatic glucose production may predominantly reflect their action on insulin and glucagon secretion; (b) after oral glucose, alpha- and beta-blockers separately or combined decrease glucose release into the portal system; (c) net hepatic glucose uptake is predominantly determined by hyperglycemia but can be modulated by insulin and glucagon; (d) direct correlation does not exist between hepatic delivery and uptake of insulin and net hepatic glucose uptake; (e) alterations in oral glucose tolerance due to adrenergic blockers, beyond their effects on glucose absorption, can be, to a large extent, mediated by their effects on insulin and glucagon secretion reflecting both hepatic and peripheral glucose metabolism. PMID:2870078

  14. Diurnal Variation in Response to Intravenous Glucose*

    PubMed Central

    Whichelow, Margaret J.; Sturge, R. A.; Keen, H.; Jarrett, R. J.; Stimmler, L.; Grainger, Susan

    1974-01-01

    Intravenous glucose tolerance tests (25 g) were performed in the morning and afternoon on 13 apparently normal persons. The individual K values (rate of decline of blood sugar) were all higher in the morning tests, and the mean values were significantly higher in the morning. Fasting blood sugar levels were slightly lower in the afternoon. There was no difference between the fasting morning and afternoon plasma insulin levels, but the levels after glucose were lower in the afternoon. Growth hormone levels were low at all times in non-apprehensive subjects and unaffected by glucose. The results suggest that the impaired afternoon intravenous glucose tolerance, like oral glucose tolerance, is associated with impaired insulin release and insulin resistance. PMID:4817160

  15. Investigating brain metabolism at high fields using localized 13C NMR spectroscopy without 1H decoupling.

    PubMed

    Deelchand, Dinesh Kumar; Uğurbil, Kâmil; Henry, Pierre-Gilles

    2006-02-01

    Most in vivo 13C NMR spectroscopy studies in the brain have been performed using 1H decoupling during acquisition. Decoupling imposes significant constraints on the experimental setup (particularly for human studies at high magnetic field) in order to stay within safety limits for power deposition. We show here that incorporation of the 13C label from 13C-labeled glucose into brain amino acids can be monitored accurately using localized 13C NMR spectroscopy without the application of 1H decoupling. Using LCModel quantification with prior knowledge of one-bond and multiple-bond J(CH) coupling constants, the uncertainty on metabolites concentrations was only 35% to 91% higher (depending on the carbon resonance of interest) in undecoupled spectra compared to decoupled spectra in the rat brain at 9.4 Tesla. Although less sensitive, 13C NMR without decoupling dramatically reduces experimental constraints on coil setup and pulse sequence design required to keep power deposition within safety guidelines. This opens the prospect of safely measuring 13C NMR spectra in humans at varied brain locations (not only the occipital lobe) and at very high magnetic fields above 4 Tesla. PMID:16345037

  16. Glucose determination with fiber optic spectrometers

    NASA Astrophysics Data System (ADS)

    Starke, Eva; Kemper, Ulf; Barschdorff, Dieter

    1999-05-01

    Noninvasive blood glucose monitoring is the aim of research activities concerning the detection of small glucose concentrations dissolved in water and blood plasma. One approach for these measurements is the exploitation of absorption bands in the near infrared. However, the strong absorption of water represents a major difficulty. Transmission measurements of glucose dissolved in water and in blood plasma in the spectral region around 1600 nm with one- beam spectrometers and a FT-IR spectrometer are discussed. The evaluation of the data is carried out using a two-layer Lambert-Beer model and neural networks. In order to reduce the dimensions of a potential measuring device, an integrated acousto-optic tunable filter (AOTF) with an Erbium doped fiber amplifier as a radiation source is used. The fiber optic components are examined concerning their suitability. The smallest concentrations of glucose dissolved in water that can be separated are approximately 50 mg/dl. In the range of 50 mg/dl to 1000 mg/dl a correlation coefficient of 0.98 between real and estimated glucose concentrations is achieved using neural networks. In blood plasma so far glucose concentrations of about 100 mg/dl can be distinguished with good accuracy.

  17. Blood Test: Glucose

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Blood Test: Glucose KidsHealth > For Parents > Blood Test: Glucose Print A A A Text Size What's in ... de sangre: glucosa What It Is A blood glucose test measures the amount of glucose (the main ...

  18. 4D prediction of protein (1)H chemical shifts.

    PubMed

    Lehtivarjo, Juuso; Hassinen, Tommi; Korhonen, Samuli-Petrus; Peräkylä, Mikael; Laatikainen, Reino

    2009-12-01

    A 4D approach for protein (1)H chemical shift prediction was explored. The 4th dimension is the molecular flexibility, mapped using molecular dynamics simulations. The chemical shifts were predicted with a principal component model based on atom coordinates from a database of 40 protein structures. When compared to the corresponding non-dynamic (3D) model, the 4th dimension improved prediction by 6-7%. The prediction method achieved RMS errors of 0.29 and 0.50 ppm for Halpha and HN shifts, respectively. However, for individual proteins the RMS errors were 0.17-0.34 and 0.34-0.65 ppm for the Halpha and HN shifts, respectively. X-ray structures gave better predictions than the corresponding NMR structures, indicating that chemical shifts contain invaluable information about local structures. The (1)H chemical shift prediction tool 4DSPOT is available from http://www.uku.fi/kemia/4dspot . PMID:19876601

  19. Hepatic Carboxylesterase 1 Is Induced by Glucose and Regulates Postprandial Glucose Levels

    PubMed Central

    Xu, Jiesi; Yin, Liya; Xu, Yang; Li, Yuanyuan; Zalzala, Munaf; Cheng, Gang; Zhang, Yanqiao

    2014-01-01

    Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1) is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, glucose stimulated CES1 promoter activity and increased acetylation of histone 3 and histone 4 in the CES1 chromatin. Knockdown of ATP-citrate lyase (ACL), an enzyme that regulates histone acetylation, abolished glucose-mediated histone acetylation in the CES1 chromatin and glucose-induced hepatic CES1 expression. Finally, knockdown of hepatic CES1 significantly increased postprandial blood glucose levels. In conclusion, the present study uncovers a novel glucose-CES1-glucose pathway which may play an important role in regulating postprandial blood glucose levels. PMID:25285996

  20. Serial 1H-MRS in GM2 gangliosidoses.

    PubMed

    Assadi, Mitra; Baseman, Susan; Janson, Christopher; Wang, Dah-Jyuu; Bilaniuk, Larissa; Leone, Paola

    2008-03-01

    GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. Clinically, the disease is marked by a relentless encephalopathy. Proton magnetic resonance spectroscopy (1H-MRS) provides in-vivo measurement of various brain metabolites including N-acetyl aspartate+N-acetyl aspartate glutamate (NAA), myo-inositol (mI), choline (Cho) and creatine (Cr). The NAA represents neuronal integrity while elevation in the mI reflects abnormal inflammation and gliosis in the brain tissue. An elevation in the Cho levels suggest cell membrane breakdown and demyelination. We report the clinical and laboratory data in two patients with GM2 gangliosidoses. Serial 1H-MRS evaluations were performed to drive metabolite ratios of NAA/Cr, mI/Cr and Cho/Cr. We acquired the data from four regions of interest (ROI) according to a standard protocol. The results documented a progressive elevation in mI/Cr in all four ROI in patient one and only one ROI (occipital gray matter) in patient 2. We also documented a decline in the NAA/Cr ratios in both cases in most ROI. These results were compared to six age-matched controls and confirmed statistically significant elevation in the mI in our cases. In conclusion, 1H-MRS alterations were suggestive of neuronal loss and inflammation in these patients. 1H-MRS may be a valuable tool in monitoring the disease progress and response to therapy in GM2 gangliosidoses. Elevation in the mI may prove to be more sensitive than the other metabolite alterations. PMID:17387512

  1. Laundering and Deinking Applications of 1H NMR Imaging

    NASA Astrophysics Data System (ADS)

    Tutunjian, P. N.; Borchardt, J. K.; Prieto, N. E.; Raney, K. H.; Ferris, J. A.

    One-dimensional 1H NMR imaging techniques are used to visualize oil removal from fabrics and paper fibers immersed in aqueous solutions of nonionic detergents. The method provides a unique approach to the study of oil-removal kinetics in nonionic detergent systems where traditional optical techniques fail due to solution turbidity. The only requirement of the NMR experiment is the use of deuterated water in order to selectively image the hydrocarbon phase. Preliminary applications to laundering and paper deinking are discussed.

  2. 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

    2016-05-01

    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. PMID:26940240

  3. Sleep restriction acutely impairs glucose tolerance in rats.

    PubMed

    Jha, Pawan K; Foppen, Ewout; Kalsbeek, Andries; Challet, Etienne

    2016-06-01

    Chronic sleep curtailment in humans has been related to impairment of glucose metabolism. To better understand the underlying mechanisms, the purpose of the present study was to investigate the effect of acute sleep deprivation on glucose tolerance in rats. A group of rats was challenged by 4-h sleep deprivation in the early rest period, leading to prolonged (16 h) wakefulness. Another group of rats was allowed to sleep during the first 4 h of the light period and sleep deprived in the next 4 h. During treatment, food was withdrawn to avoid a postmeal rise in plasma glucose. An intravenous glucose tolerance test (IVGTT) was performed immediately after the sleep deprivation period. Sleep deprivation at both times of the day similarly impaired glucose tolerance and reduced the early-phase insulin responses to a glucose challenge. Basal concentrations of plasma glucose, insulin, and corticosterone remained unchanged after sleep deprivation. Throughout IVGTTs, plasma corticosterone concentrations were not different between the control and sleep-deprived group. Together, these results demonstrate that independent of time of day and sleep pressure, short sleep deprivation during the resting phase favors glucose intolerance in rats by attenuating the first-phase insulin response to a glucose load. In conclusion, this study highlights the acute adverse effects of only a short sleep restriction on glucose homeostasis. PMID:27354542

  4. Influence of Continuous Physiologic Hyperinsulinemia on Glucose Kinetics and Counterregulatory Hormones in Normal and Diabetic Humans

    PubMed Central

    Saccà, Luigi; Sherwin, Robert; Hendler, Rosa; Felig, Philip

    1979-01-01

    The effects of continuous infusions of insulin in physiologic doses on glucose kinetics and circulating counterregulatory hormones (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) were determined in normal subjects and diabetics. The normals received insulin at two dose levels (0.4 and 0.25 mU/kg per min) and the diabetics received the higher dose (0.4 mU/kg per min) only. In all three groups of studies, continuous infusion of insulin resulted in an initial decline in plasma glucose followed by stabilization after 60-180 min. In the normal subjects, with the higher insulin dose there was a fivefold rise in plasma insulin. Plasma glucose fell at a rate of 0.73±0.12 mg/min for 45 min and then stabilized at 55±3 mg/dl after 60 min. The initial decline in plasma glucose was a result of a rapid, 27% fall in glucose output and a 33% rise in glucose uptake. Subsequent stabilization was a result of a return of glucose output and uptake to basal levels. The rebound increment in glucose output was significant (P < 0.05) by 30 min after initiation of the insulin infusion and preceded, by 30-45 min, a significant rise in circulating counterregulatory hormones. With the lower insulin infusion dose, plasma insulin rose two- to threefold, plasma glucose initially fell at a rate of 0.37±0.04 mg/min for 75 min and stabilized at 67±3 mg/dl after 75 min. The changes in plasma glucose were entirely a result of a fall in glucose output and subsequent return to base line, whereas glucose uptake remained unchanged. Plasma levels of counterregulatory hormones showed no change from basal throughout the insulin infusion. In the diabetic group (plasma glucose levels 227±7 mg/dl in the basal state), the initial rate of decline in plasma glucose (1.01±0.15 mg/dl) and the plateau concentration of plasma glucose (59±5 mg/dl) were comparable to controls receiving the same insulin dose. However, the initial fall in plasma glucose was almost entirely a result of

  5. Proton-detected 3D 1H/13C/1H correlation experiment for structural analysis in rigid solids under ultrafast-MAS above 60 kHz

    NASA Astrophysics Data System (ADS)

    Zhang, Rongchun; Nishiyama, Yusuke; Ramamoorthy, Ayyalusamy

    2015-10-01

    A proton-detected 3D 1H/13C/1H chemical shift correlation experiment is proposed for the assignment of chemical shift resonances, identification of 13C-1H connectivities, and proximities of 13C-1H and 1H-1H nuclei under ultrafast magic-angle-spinning (ultrafast-MAS) conditions. Ultrafast-MAS is used to suppress all anisotropic interactions including 1H-1H dipolar couplings, while the finite-pulse radio frequency driven dipolar recoupling (fp-RFDR) pulse sequence is used to recouple dipolar couplings among protons and the insensitive nuclei enhanced by polarization transfer technique is used to transfer magnetization between heteronuclear spins. The 3D experiment eliminates signals from non-carbon-bonded protons and non-proton-bonded carbons to enhance spectral resolution. The 2D (F1/F3) 1H/1H and 2D 13C/1H (F2/F3) chemical shift correlation spectra extracted from the 3D spectrum enable the identification of 1H-1H proximity and 13C-1H connectivity. In addition, the 2D (F1/F2) 1H/13C chemical shift correlation spectrum, incorporated with proton magnetization exchange via the fp-RFDR recoupling of 1H-1H dipolar couplings, enables the measurement of proximities between 13C and even the remote non-carbon-bonded protons. The 3D experiment also gives three-spin proximities of 1H-1H-13C chains. Experimental results obtained from powder samples of L-alanine and L-histidine ṡ H2O ṡ HCl demonstrate the efficiency of the 3D experiment.

  6. Detection of intracellular lactate with localized diffusion { 1H- 13C}-spectroscopy in rat glioma in vivo

    NASA Astrophysics Data System (ADS)

    Pfeuffer, Josef; Lin, Joseph C.; DelaBarre, Lance; Ugurbil, Kamil; Garwood, Michael

    2005-11-01

    The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of 13C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). 13C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, { 1H- 13C}-lactate and { 1H- 13C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into { 1H- 13C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/μm 2). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, 1H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([ 13C] lactate) originates from an intracellular compartment.

  7. Glucose metabolism in patients with Cushing's syndrome.

    PubMed

    Bowes, S B; Benn, J J; Scobie, I N; Umpleby, A M; Lowy, C; Sönksen, P H

    1991-04-01

    Glucose intolerance, sometimes severe enough to cause frank diabetes mellitus, is a frequent feature of Cushing's syndrome. The primary cause of the hyperglycaemia, whether due to glucose over-production or under-utilization, remains unresolved. We therefore measured glucose turnover using an intravenous bolus of 3-3H glucose in 14 normoglycaemic patients with Cushing's syndrome and 14 control subjects. Seven of the patients with Cushing's syndrome were also restudied post-operatively. Plasma glucose concentrations were similar in all three groups whereas glucose metabolic clearance rate (MCR) (1.80 +/- 0.06 ml/min/kg) and glucose turnover rate (9.09 +/- 0.36 mumol/min/kg) were significantly reduced in patients with Cushing's syndrome compared to normal subjects (2.21 +/- 0.1; P less than 0.001; 10.90 +/- 0.50; P less than 0.01) and rose post-operatively to normal values (2.35 +/- 0.14 ml/min/kg; 11.07 +/- 0.48 mumol/min/kg). We conclude from these results that the hyperglycaemia sometimes found in Cushing's syndrome may be primarily due to decreased utilization rather than increased glucose production. PMID:1879061

  8. The regulation of glucose transport in the heart of control and diabetic rats: With special emphasis on the glucose transporter

    SciTech Connect

    Pleta, M. de Leoz.

    1989-01-01

    Glucose transport regulation with insulin and high perfusion pressure in the perfused rat hearts from control and diabetic rat hearts was investigated. ({sup 3}H)-cytochalasin B binding assay was used to study the distribution of glucose transporters within the subcellular membranes fractionated by linear sucrose density gradient centrifugation. In the present study, insulin increased glucose uptake in the perfused heart of control and diabetic animals. This coincided with an increase of glucose transporters on the plasma membrane. The increase in glucose transporters on the plasma membrane could not be accounted for by a decrease of glucose transporters from the microsomal membranes. High perfusion pressure did not change the number of glucose transporters on the plasma membrane compared to basal in the control and diabetic animals, though it increased glucose uptake above that observed for insulin in the control. Instead, high perfusion pressure altered the distribution of glucose transporters within the subcellular membranes in reverse to that with insulin, increasing an intermediate membrane pool believed to reside between the plasma membrane and microsomal membranes as well as the intracellular membrane pool.

  9. Proton-detected 3D 14N/14N/1H isotropic shift correlation experiment mediated through 1H-1H RFDR mixing on a natural abundant sample under ultrafast MAS

    NASA Astrophysics Data System (ADS)

    Pandey, Manoj Kumar; Nishiyama, Yusuke

    2015-09-01

    In this contribution, we have demonstrated a proton detection-based approach on a natural abundant powdered L-Histidine HCl-H2O sample at ultrafast magic angle spinning (MAS) to accomplish 14N/14N correlation from a 3D 14N/14N/1H isotropic shift correlation experiment mediated through 1H finite-pulse radio frequency-driven recoupling (fp-RFDR). Herein the heteronuclear magnetization transfer between 14N and 1H has been achieved by HMQC experiment, whereas 14N/14N correlation is attained through enhanced 1H-1H spin diffusion process due to 1H-1H dipolar recoupling during the RFDR mixing. While the use of ultrafast MAS (90 kHz) provides sensitivity enhancement through increased 1H transverse relaxation time (T2), the use of micro-coil probe which can withstand strong 14N radio frequency (RF) fields further improves the sensitivity per unit sample volume.

  10. Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure.

    PubMed

    Olea, Elena; Agapito, Maria Teresa; Gallego-Martin, Teresa; Rocher, Asuncion; Gomez-Niño, Angela; Obeso, Ana; Gonzalez, Constancio; Yubero, Sara

    2014-10-01

    Obstructive sleep apnea (OSA) consists of sleep-related repetitive obstructions of upper airways that generate episodes of recurrent or intermittent hypoxia (IH). OSA commonly generates cardiovascular and metabolic pathologies defining the obstructive sleep apnea syndrome (OSAS). Literature usually links OSA-associated pathologies to IH episodes that would cause an oxidative status and a carotid body-mediated sympathetic hyperactivity. Because cardiovascular and metabolic pathologies in obese patients and those with OSAS are analogous, we used models (24-wk-old Wistar rats) of IH (applied from weeks 22 to 24) and diet-induced obesity (O; animals fed a high-fat diet from weeks 12 to 24) to define the effect of each individual maneuver and their combination on the oxidative status and sympathetic tone of animals, and to quantify cardiovascular and metabolic parameters and their deviation from normality. We found that IH and O cause an oxidative status (increased lipid peroxides and diminished activities of superoxide dismutases), an inflammatory status (augmented C-reactive protein and nuclear factor kappa-B activation), and sympathetic hyperactivity (augmented plasma and renal artery catecholamine levels and synthesis rate); combined treatments worsened those alterations. IH and O augmented liver lipid content and plasma cholesterol, triglycerides, leptin, glycemia, insulin levels, and HOMA index, and caused hypertension; most of these parameters were aggravated when IH and O were combined. IH diminished ventilatory response to hypoxia, and hypercapnia and O created a restrictive ventilatory pattern; a combination of treatments led to restrictive hypoventilation. Data demonstrate that IH and O cause comparable metabolic and cardiovascular pathologies via misregulation of the redox status and sympathetic hyperactivity. PMID:25103975

  11. Hydrogen concentration dependence of 1H Knight shift in NbH x studied by 1H MAS NMR

    NASA Astrophysics Data System (ADS)

    Ueda, Takahiro; Hayashi, Shigenobu; Hayamizu, Kikuko

    1993-08-01

    Hydrogen concentration dependence of the Knight shift of protons in NbH x(0.05≤×≤1.05) has been studied by means of 1H MAS (magic angle sample spinning) NMR. In the mixed-phase samples of the α and β phases (0.05<×≤0.7), it is found that the 1H Knight shift of β-NbH x depends on the phase fraction. The shift variation in the β phase can be correlated with the unit cell volume, being explained by the variation of the density of electronic states at the Fermi level N(0) due to the compression of the crystal lattice. On the other hand, in the single β-phase samples (0.7<×≤1.05), the 1H Knight shift becomes smaller as the hydrogen concentration increases. This variation can be explained by increase in the number of electrons in the unit cell with the hydrogen concentration, resulting in the N(0) increase.

  12. Campath-1H + FK506 and Methylprednisolone for GVHD

    ClinicalTrials.gov

    2010-06-10

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  13. Dynamic 1H NMR Studies of Schiff Base Derivatives

    NASA Astrophysics Data System (ADS)

    Köylü, M. Z.; Ekinci, A.; Böyükata, M.; Temel, H.

    2016-01-01

    The spin-lattice relaxation time T 1 and the spin-spin relaxation time T 2 of two Schiff base derivatives, N,N'-ethylenebis(salicylidene)-1,2-diaminoethane (H2L1) and N,N'-ethylenebis (salicylidene)-1,3-diaminopropane (H2L2), in DMSO-d6 solvent were studied as a function of temperature in the range of 20-50°C using a Bruker Avance 400.132 MHz 1H NMR spectrometer. Based on the activation energy ( E a) and correlation time (τc), we believe that the Schiff base derivatives perform a molecular tumbling motion.

  14. The 1H NMR Profile of Healthy Dog Cerebrospinal Fluid

    PubMed Central

    Musteata, Mihai; Nicolescu, Alina; Solcan, Gheorghe; Deleanu, Calin

    2013-01-01

    The availability of data for reference values in cerebrospinal fluid for healthy humans is limited due to obvious practical and ethical issues. The variability of reported values for metabolites in human cerebrospinal fluid is quite large. Dogs present great similarities with humans, including in cases of central nervous system pathologies. The paper presents the first study on healthy dog cerebrospinal fluid metabolomic profile using 1H NMR spectroscopy. A number of 13 metabolites have been identified and quantified from cerebrospinal fluid collected from a group of 10 mix breed healthy dogs. The biological variability as resulting from the relative standard deviation of the physiological concentrations of the identified metabolites had a mean of 18.20% (range between 9.3% and 44.8%). The reported concentrations for metabolites may be used as normal reference values. The homogeneity of the obtained results and the low biologic variability show that the 1H NMR analysis of the dog’s cerebrospinal fluid is reliable in designing and interpreting clinical and therapeutic trials in dogs with central nervous system pathologies. PMID:24376499

  15. Glucose-6-phosphate dehydrogenase

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a type of ...

  16. Your Glucose Meter

    MedlinePlus

    ... by Audience For Women Women's Health Topics Your Glucose Meter Share Tweet Linkedin Pin it More sharing ... Español Basic Facts 7 Tips for Testing Your Blood Sugar and Caring for Your Meter Glucose meters test ...

  17. Continuous Glucose Monitoring

    MedlinePlus

    ... catalog. Additional Links ​ Alternative Devices for Taking Insulin Children and Diabetes Glucose Meters Juvenile Diabetes (Teens and Diabetes ) Know Your Blood Glucose Numbers Your Guide to Diabetes: Type 1 and Type 2 Contact Us Health Information Center ...

  18. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism.

    PubMed

    Galindo, C; Larsen, M; Ouellet, D R; Maxin, G; Pellerin, D; Lapierre, H

    2015-11-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate (BHBA) in postpartum dairy cows according to a generalized randomized incomplete block design with repeated measures in time. At calving, cows were blocked according to parity (second and third or greater) and were allocated to 2 treatments: abomasal infusion of water (n=4) or abomasal infusion of free AA with casein profile (AA-CN; n=5) in addition to the same basal diet. The AA-CN infusion started with half the maximal dose at 1 d in milk (DIM) and then steadily decreased from 791 to 226 g/d from DIM 2 to 29 to cover the estimated essential AA deficit. On DIM 5, 15, and 29, D[6,6-(2)H2]-glucose (23.7 mmol/h) was infused into a jugular vein for 5h, and 6 blood samples were taken from arterial, portal, hepatic, and mammary sources at 45-min intervals, starting 1h after the initiation of the D[6,6-(2)H2]glucose infusion. Trans-organ fluxes were calculated as veno-arterial differences times plasma flow (splanchnic: downstream dilution of deacetylated para-aminohippurate; mammary: Fick principle using Phe+Tyr). Energy-corrected milk and lactose yields increased on average with AA-CN by 6.4 kg/d and 353 g/d, respectively, with no DIM × treatment interaction. Despite increased AA supply and increased demand for lactose secretion with AA-CN, net hepatic release of glucose remained unchanged, but WB-Ra of glucose tended to increase with AA-CN. Portal true flux of glucose increased with AA-CN and represented, on average, 17% of WB-Ra. Splanchnic true flux of glucose was unaltered by treatments and was numerically equivalent to WB-Ra, averaging 729 and 741 mmol/h, respectively. Mammary glucose utilization increased with AA-CN infusion, averaging 78% of WB-Ra, and increased

  19. Glucose-lowering effects of intestinal bile acid sequestration through enhancement of splanchnic glucose utilization.

    PubMed

    Prawitt, Janne; Caron, Sandrine; Staels, Bart

    2014-05-01

    Intestinal bile acid (BA) sequestration efficiently lowers plasma glucose concentrations in type 2 diabetes (T2D) patients. Because BAs act as signaling molecules via receptors, including the G protein-coupled receptor TGR5 and the nuclear receptor FXR (farnesoid X receptor), to regulate glucose homeostasis, BA sequestration, which interrupts the entero-hepatic circulation of BAs, constitutes a plausible action mechanism of BA sequestrants. An increase of intestinal L-cell glucagon-like peptide-1 (GLP-1) secretion upon TGR5 activation is the most commonly proposed mechanism, but recent studies also argue for a direct entero-hepatic action to enhance glucose utilization. We discuss here recent findings on the mechanisms of sequestrant-mediated glucose lowering via an increase of splanchnic glucose utilization through entero-hepatic FXR signaling. PMID:24731596

  20. Identification of Glucose Transporters in Aspergillus nidulans

    PubMed Central

    dos Reis, Thaila Fernanda; Menino, João Filipe; Bom, Vinícius Leite Pedro; Brown, Neil Andrew; Colabardini, Ana Cristina; Savoldi, Marcela; Goldman, Maria Helena S.; Rodrigues, Fernando; Goldman, Gustavo Henrique

    2013-01-01

    To characterize the mechanisms involved in glucose transport, in the filamentous fungus Aspergillus nidulans, we have identified four glucose transporter encoding genes hxtB-E. We evaluated the ability of hxtB-E to functionally complement the Saccharomyces cerevisiae EBY.VW4000 strain that is unable to grow on glucose, fructose, mannose or galactose as single carbon source. In S. cerevisiae HxtB-E were targeted to the plasma membrane. The expression of HxtB, HxtC and HxtE was able to restore growth on glucose, fructose, mannose or galactose, indicating that these transporters accept multiple sugars as a substrate through an energy dependent process. A tenfold excess of unlabeled maltose, galactose, fructose, and mannose were able to inhibit glucose uptake to different levels (50 to 80 %) in these s. cerevisiae complemented strains. Moreover, experiments with cyanide-m-chlorophenylhydrazone (CCCP), strongly suggest that hxtB, -C, and –E mediate glucose transport via active proton symport. The A. nidulans ΔhxtB, ΔhxtC or ΔhxtE null mutants showed ~2.5-fold reduction in the affinity for glucose, while ΔhxtB and -C also showed a 2-fold reduction in the capacity for glucose uptake. The ΔhxtD mutant had a 7.8-fold reduction in affinity, but a 3-fold increase in the capacity for glucose uptake. However, only the ΔhxtB mutant strain showed a detectable decreased rate of glucose consumption at low concentrations and an increased resistance to 2-deoxyglucose. PMID:24282591

  1. Dynamics-based selective 2D (1)H/(1)H chemical shift correlation spectroscopy under ultrafast MAS conditions.

    PubMed

    Zhang, Rongchun; Ramamoorthy, Ayyalusamy

    2015-05-28

    Dynamics plays important roles in determining the physical, chemical, and functional properties of a variety of chemical and biological materials. However, a material (such as a polymer) generally has mobile and rigid regions in order to have high strength and toughness at the same time. Therefore, it is difficult to measure the role of mobile phase without being affected by the rigid components. Herein, we propose a highly sensitive solid-state NMR approach that utilizes a dipolar-coupling based filter (composed of 12 equally spaced 90° RF pulses) to selectively measure the correlation of (1)H chemical shifts from the mobile regions of a material. It is interesting to find that the rotor-synchronized dipolar filter strength decreases with increasing inter-pulse delay between the 90° pulses, whereas the dipolar filter strength increases with increasing inter-pulse delay under static conditions. In this study, we also demonstrate the unique advantages of proton-detection under ultrafast magic-angle-spinning conditions to enhance the spectral resolution and sensitivity for studies on small molecules as well as multi-phase polymers. Our results further demonstrate the use of finite-pulse radio-frequency driven recoupling pulse sequence to efficiently recouple weak proton-proton dipolar couplings in the dynamic regions of a molecule and to facilitate the fast acquisition of (1)H/(1)H correlation spectrum compared to the traditional 2D NOESY (Nuclear Overhauser effect spectroscopy) experiment. We believe that the proposed approach is beneficial to study mobile components in multi-phase systems, such as block copolymers, polymer blends, nanocomposites, heterogeneous amyloid mixture of oligomers and fibers, and other materials. PMID:26026440

  2. Blood Sugar Measurement in Zebrafish Reveals Dynamics of Glucose Homeostasis

    PubMed Central

    Eames, Stefani C.; Philipson, Louis H.; Prince, Victoria E.

    2010-01-01

    Abstract The adult zebrafish has the potential to become an important model for diabetes-related research. To realize this potential, small-scale methods for analyzing pancreas function are required. The measurement of blood glucose level is a commonly used method for assessing β-cell function, but the small size of the zebrafish presents challenges both for collecting blood samples and for measuring glucose. We have developed methods for collecting microsamples of whole blood and plasma for the measurement of hematocrit and blood glucose. We demonstrate that two hand-held glucose meters designed for use by human diabetics return valid results with zebrafish blood. Additionally, we present methods for fasting and for performing postprandial glucose and intraperitoneal glucose tolerance tests. We find that the dynamics of zebrafish blood glucose homeostasis are consistent with patterns reported for other omnivorous teleost fish. PMID:20515318

  3. CSF glucose test

    MedlinePlus

    Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 to 80 mg/100 mL (or greater than 2/3 of the blood sugar level). Note: Normal value ranges may vary slightly ...

  4. Effects of Different Proportion of Carbohydrate in Breakfast on Postprandial Glucose Excursion in Normal Glucose Tolerance and Impaired Glucose Regulation Subjects

    PubMed Central

    Kang, Xin; Wang, Chun; Lifang, Lv; Chen, Dawei; Yang, Yanzhi; Liu, Guanjian; Wen, Hu; Chen, Lihong; He, Liping; Li, Xiujun; Tian, Haoming; Jia, Weiping

    2013-01-01

    Abstract Background The variability of postprandial plasma glucose is an independent risk factor for diabetes. The type and amount of carbohydrate may be important determinants of glycemic control. The aim of the study was to compare the effects of different proportions of carbohydrate in breakfast on postprandial blood glucose fluctuations in impaired glucose regulation (IGR) and normal glucose tolerance (NGT) subjects. Subjects and Methods This is a cross-sectional study of two groups including 55 subjects with IGR and 78 individuals with NGT. Their recorded breakfast was sorted into low-carbohydrate (LC) (carbohydrate <45%), medium-carbohydrate (MC) (carbohydrate 45–65%), and high-carbohydrate (HC) (carbohydrate >65%) meals according to the proportion of carbohydrate. Glucose concentrations were continuously measured with a continuous glucose monitoring system, and parameters such as the incremental area under the curve (iAUC) of glucose and postprandial glucose excursion (PPGE) were calculated to evaluate postprandial glucose fluctuations. Results The postprandial fluctuations of glucose increased gradually with increased proportions of carbohydrate in breakfast in both IGR and NGT subjects. For the MC and HC meals, iAUC, PPGE, postprandial glucose spike (PGS), and mean blood glucose were significantly greater than those in the NGT group (P<0.05), respectively. The median time to PGS and the time period in which glucose concentrations decreased to baseline after the MC and HC meals in the IGR group were significantly longer than those in the NGT group (P<0.01), respectively. Compared with the NGT subjects for the HC meal, the IGR subjects consuming the MC meal had greater PGS, range of glucose concentrations, SD, and PPGE (P<0.05). Conclusions The proportion of carbohydrate in breakfast contributes to glucose excursions in the NGT and IGR subjects. In the IGR subjects, a HC meal should be avoided and a LC meal should be recommended to prevent development of

  5. Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics

    SciTech Connect

    Feng, Ju; Isern, Nancy G.; Burton, Sarah D.; Hu, Jian Z.

    2013-10-31

    NMR metabolomics, consisting of solid state high resolution (hr) magic angle spinning (MAS) 1H NMR (1H hr-MAS), liquid state high resolution 1H-NMR, and principal components analysis (PCA) has been used to study secondary metastatic B16-F10 melanoma in C57BL/6J mouse liver . The melanoma group can be differentiated from its control group by PCA analysis of the absolute concentrations or by the absolute peak intensities of metabolites from either 1H hr-MAS NMR data on intact liver tissues or liquid state 1H-NMR spectra on liver tissue extracts. In particular, we found that the absolute concentrations of alanine, glutamate, creatine, creatinine, fumarate and cholesterol are elevated in the melanoma group as compared to controls, while the absolute concentrations of succinate, glycine, glucose, and the family of linear lipids including long chain fatty acids, total choline and acylglycerol are decreased. The ratio of glycerophosphocholine to phosphocholine is increased by about 1.5 fold in the melanoma group, while the absolute concentration of total choline is actually lower in melanoma mice. These results suggest the following picture in secondary melanoma metastasis: Linear lipid levels are decreased by beta oxidation in the melanoma group, which contributes to an increase in the synthesis of cholesterol, and also provides an energy source input for TCA cycle. These findings suggest a link between lipid oxidation, the TCA cycle and the hypoxia-inducible factors (HIF) signal pathway in tumor metastases. Thus this study indicates that the metabolic profile derived from NMR analysis can provide a valuable bio-signature of malignancy and cell hypoxia in metastatic melanoma.

  6. Genetic Variation in Myosin 1H Contributes to Mandibular Prognathism

    PubMed Central

    Tassopoulou-Fishell, Maria; Deeley, Kathleen; Harvey, Erika M.; Sciote, James; Vieira, Alexandre R.

    2013-01-01

    Introduction Several candidate loci have been suggested as influencing mandibular prognathism (1p22.1, 1p22.2, 1p36, 3q26.2, 5p13-p12, 6q25, 11q22.2-q22.3, 12q23, 12q13.13, and 19p13.2). The goal of this study was to replicate these results in a well-characterized homogeneous sample set. Methods Thirty-three single nucleotide polymorphisms spanning all candidate regions were studied in 44 prognathic and 35 Class I subjects from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository. The 44 mandibular prognathism subjects had an average age of 18.4 years, 31 were females and 13 males, and 24 were White, 15 African American, two Hispanic, and three Asian. The 35 Class I subjects had an average age of 17.6 years, 27 were females and 9 males, and 27 were White, six African Americans, one Hispanic, and two Asian. Skeletal mandibular prognathism diagnosis included cephalometric values indicative of Class III such as ANB smaller than two degrees, negative Witts appraisal, and positive A–B plane. Additional mandibular prognathism criteria included negative OJ and visually prognathic (concave) profile as determined by the subject's clinical evaluation. Orthognathic subjects without jaw deformations were used as a comparison group. Mandibular prognathism and orthognathic subjects were matched based on race, sex and age. Genetic markers were tested by polymerase chain reaction using TaqMan chemistry. Chi-square and Fisher exact tests were used to determine overrepresentation of marker allele with alpha of 0.05. Results An association was unveiled between a marker in MYO1H (rs10850110) and the mandibular prognathism phenotype (p=0.03). MYO1H is a Class-I myosin that is in a different protein group than the myosin isoforms of muscle sarcomeres, which are the basis of skeletal muscle fiber typing. Class I myosins are necessary for cell motility, phagocytosis and vesicle transport. Conclusions More strict clinical definitions may increase

  7. (1)H NMR based metabolomic profiling revealed doxorubicin-induced systematic alterations in a rat model.

    PubMed

    Niu, Qian-Yun; Li, Zhen-Yu; Du, Guan-Hua; Qin, Xue-Mei

    2016-01-25

    Doxorubicin (DOX) is used as a chemotherapy drug with severe carditoxicity. In this study, an integrated echocardiography along with pathological examination and (1)H NMR analysis of multiple biological matrices (urine, serum, heart, and kidney) was employed to systemically assess the toxicity of DOX. Echocardiographic results showed that impaired left ventricular contractility and degenerative pathology lesions in DOX group, which were in consistent with pathology. The endogenous metabolites in the urine, serum, heart and kidney was identified by comparison with the data from the literature and databases. Multivariate analysis, including PCA and OPLS, revealed 8 metabolites in urine, including succinate, 2-ketoglutarate, citrate, hippurate, methylamine, benzoate, allantion, and acetate were the potential changed biomarkers. In serum, perturbed metabolites include elevation of leucine, β-glucose, O-acetyl-glycoprotein, creatine, lysine, glycerin, dimethylglycine, trimethylamine-N-oxide, myo-inositol, and N-acetyl-glycoprotein, together with level decreases of acetone, lipid, lactate, glutamate, phosphocholine, acetoacetate and pyruvate. For heart, DOX exposure caused decline of lipid, lactate, leucine, alanine, glutamate, choline, xanthine, glycerin, carnitine, and fumarate, together with elevation of glutamine, creatine, inosine, taurine and malate. Metabolic changes of kidney were mainly involved in the accumulation of α-glucose, lactate, phosphocholine, betaine, threonine, choline, taurine, glycine, urea, hypoxanthine, glutamate, and nicotinamide, coupled with reduction of asparagine, valine, methionine, tyrosine, lysine, alanine, leucine, ornithine, creatine, lipid, and acetate. In addition, alterations of urinary metabolites exhibited a time-dependent manner. Complementary evidences by multiple matrices revealed disturbed pathways concerning energy metabolism, fatty acids oxidation, amino acids and purine metabolism, choline metabolism, and gut microbiota

  8. 1H nuclear magnetic resonance-based extracellular metabolomic analysis of multidrug resistant Tca8113 oral squamous carcinoma cells

    PubMed Central

    WANG, HUI; CHEN, JIAO; FENG, YUN; ZHOU, WENJIE; ZHANG, JIHUA; YU, YU; WANG, XIAOQIAN; ZHANG, PING

    2015-01-01

    A major obstacle of successful chemotherapy is the development of multidrug resistance (MDR) in the cancer cells, which is difficult to reverse. Metabolomic analysis, an emerging approach that has been increasingly applied in various fields, is able to reflect the unique chemical fingerprints of specific cellular processes in an organism. The assessment of such metabolite changes can be used to identify novel therapeutic biomarkers. In the present study, 1H nuclear magnetic resonance (NMR) spectroscopy was used to analyze the extracellular metabolomic spectrum of the Tca8113 oral squamous carcinoma cell line, in which MDR was induced using the carboplatin (CBP) and pingyangmycin (PYM) chemotherapy drugs in vitro. The data were analyzed using the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) methods. The results demonstrated that the extracellular metabolomic spectrum of metabolites such as glutamate, glycerophosphoethanol amine, α-Glucose and β-Glucose for the drug-induced Tca8113 cells was significantly different from the parental Tca8113 cell line. A number of biochemicals were also significantly different between the groups based on their NMR spectra, with drug-resistant cells presenting relatively higher levels of acetate and lower levels of lactate. In addition, a significantly higher peak was observed at δ 3.35 ppm in the spectrum of the PYM-induced Tca8113 cells. Therefore, 1H NMR-based metabolomic analysis has a high potential for monitoring the formation of MDR during clinical tumor chemotherapy in the future. PMID:26137105

  9. Direct determination of phosphate sugars in biological material by (1)H high-resolution magic-angle-spinning NMR spectroscopy.

    PubMed

    Diserens, Gaëlle; Vermathen, Martina; Gjuroski, Ilche; Eggimann, Sandra; Precht, Christina; Boesch, Chris; Vermathen, Peter

    2016-08-01

    The study aim was to unambiguously assign nucleotide sugars, mainly UDP-X that are known to be important in glycosylation processes as sugar donors, and glucose-phosphates that are important intermediate metabolites for storage and transfer of energy directly in spectra of intact cells, as well as in skeletal muscle biopsies by (1)H high-resolution magic-angle-spinning (HR-MAS) NMR. The results demonstrate that sugar phosphates can be determined quickly and non-destructively in cells and biopsies by HR-MAS, which may prove valuable considering the importance of phosphate sugars in cell metabolism for nucleic acid synthesis. As proof of principle, an example of phosphate-sugar reaction and degradation kinetics after unfreezing the sample is shown for a cardiac muscle, suggesting the possibility to follow by HR-MAS NMR some metabolic pathways. Graphical abstract Glucose-phosphate sugars (Glc-1P and Glc-6P) detected in muscle by 1H HR-MAS NMR. PMID:27271261

  10. Hydrophobization of epoxy nanocomposite surface with 1H,1H,2H,2H-perfluorooctyltrichlorosilane for superhydrophobic properties

    NASA Astrophysics Data System (ADS)

    Psarski, Maciej; Marczak, Jacek; Celichowski, Grzegorz; Sobieraj, Grzegorz B.; Gumowski, Konrad; Zhou, Feng; Liu, Weimin

    2012-10-01

    Nature inspires the design of synthetic materials with superhydrophobic properties, which can be used for applications ranging from self-cleaning surfaces to microfluidic devices. Their water repellent properties are due to hierarchical (micrometer- and nanometre-scale) surface morphological structures, either made of hydrophobic substances or hydrophobized by appropriate surface treatment. In this work, the efficiency of two surface treatment procedures, with a hydrophobic fluoropolymer, synthesized and deposited from 1H,1H,2H,2H-perfluorooctyltrichlorosilane (PFOTS) is investigated. The procedures involved reactions from the gas and liquid phases of the PFOTS/hexane solutions. The hierarchical structure is created in an epoxy nanocomposite surface, by filling the resin with alumina nanoparticles and micron-sized glass beads and subsequent sandblasting with corundum microparticles. The chemical structure of the deposited fluoropolymer was examined using XPS spectroscopy. The topography of the modified surfaces was characterized using scanning electron microscopy (SEM), and atomic force microscopy (AFM). The hydrophobic properties of the modified surfaces were investigated by water contact and sliding angles measurements. The surfaces exhibited water contact angles of above 150° for both modification procedures, however only the gas phase modification provided the non-sticking behaviour of water droplets (sliding angle of 3°). The discrepancy is attributed to extra surface roughness provided by the latter procedure.

  11. Determination of relative orientation between (1)H CSA tensors from a 3D solid-state NMR experiment mediated through (1)H/(1)H RFDR mixing under ultrafast MAS.

    PubMed

    Pandey, Manoj Kumar; Nishiyama, Yusuke

    2015-09-01

    To obtain piercing insights into inter and intramolecular H-bonding, and π-electron interactions measurement of (1)H chemical shift anisotropy (CSA) tensors is gradually becoming an obvious choice. While the magnitude of CSA tensors provides unique information about the local electronic environment surrounding the nucleus, the relative orientation between these tensors can offer further insights into the spatial arrangement of interacting nuclei in their respective three-dimensional (3D) space. In this regard, we present a 3D anisotropic/anisotropic/isotropic proton chemical shift (CSA/CSA/CS) correlation experiment mediated through (1)H/(1)H radio frequency-driven recoupling (RFDR) which enhances spin diffusion through recoupled (1)H-(1)H dipolar couplings under ultrafast magic angle spinning (MAS) frequency (70kHz). Relative orientation between two interacting 1H CSA tensors is obtained by fitting two-interacting (1)H CSA tensors by fitting two-dimensional (2D) (1)H/(1)H CSA/CSA spectral slices through extensive numerical simulations. To recouple (1)H CSAs in the indirect frequency dimensions of a 3D experiment we have employed γ-encoded radio frequency (RF) pulse sequence based on R-symmetry (R188(7)) with a series of phase-alternated 2700(°)-90180(°) composite-180° pulses on citric acid sample. Due to robustness of applied (1)H CSA recoupling sequence towards the presence of RF field inhomogeneity, we have successfully achieved an excellent (1)H/(1)H CSA/CSA cross-correlation efficiency between H-bonded sites of citric acid. PMID:26065628

  12. One dimensional 1H, 2H and 3H

    NASA Astrophysics Data System (ADS)

    Vidal, A. J.; Astrakharchik, G. E.; Vranješ Markić, L.; Boronat, J.

    2016-05-01

    The ground-state properties of one-dimensional electron-spin-polarized hydrogen 1H, deuterium 2H, and tritium 3H are obtained by means of quantum Monte Carlo methods. The equations of state of the three isotopes are calculated for a wide range of linear densities. The pair correlation function and the static structure factor are obtained and interpreted within the framework of the Luttinger liquid theory. We report the density dependence of the Luttinger parameter and use it to identify different physical regimes: Bogoliubov Bose gas, super-Tonks–Girardeau gas, and quasi-crystal regimes for bosons; repulsive, attractive Fermi gas, and quasi-crystal regimes for fermions. We find that the tritium isotope is the one with the richest behavior. Our results show unambiguously the relevant role of the isotope mass in the properties of this quantum system.

  13. Local hindlimb antioxidant infusion does not affect muscle glucose uptake during in situ contractions in rat.

    PubMed

    Merry, T L; Dywer, R M; Bradley, E A; Rattigan, S; McConell, G K

    2010-05-01

    There is evidence that reactive oxygen species (ROS) contribute to the regulation of skeletal muscle glucose uptake during highly fatiguing ex vivo contraction conditions via AMP-activated protein kinase (AMPK). In this study we investigated the role of ROS in the regulation of glucose uptake and AMPK signaling during low-moderate intensity in situ hindlimb muscle contractions in rats, which is a more physiological protocol and preparation. Male hooded Wistar rats were anesthetized, and then N-acetylcysteine (NAC) was infused into the epigastric artery (125 mg.kg(-1).h(-1)) of one hindlimb (contracted leg) for 15 min before this leg was electrically stimulated (0.1-ms impulse at 2 Hz and 35 V) to contract at a low-moderate intensity for 15 min. The contralateral leg did not receive stimulation or local NAC infusion (rest leg). NAC infusion increased (P<0.05) plasma cysteine and cystine (by approximately 360- and 1.4-fold, respectively) and muscle cysteine (by 1.5-fold, P=0.001). Although contraction did not significantly alter muscle tyrosine nitration, reduced (GSH) or oxidized glutathione (GSSG) content, S-glutathionylation of protein bands at approximately 250 and 150 kDa was increased (P<0.05) approximately 1.7-fold by contraction, and this increase was prevented by NAC. Contraction increased (P<0.05) skeletal muscle glucose uptake 20-fold, AMPK phosphorylation 6-fold, ACCbeta phosphorylation 10-fold, and p38 MAPK phosphorylation 60-fold, and the muscle fatigued by approximately 30% during contraction and NAC infusion had no significant effect on any of these responses. This was despite NAC preventing increases in S-glutathionylation with contraction. In conclusion, unlike during highly fatiguing ex vivo contractions, local NAC infusion during in situ low-moderate intensity hindlimb contractions in rats, a more physiological preparation, does not attenuate increases in skeletal muscle glucose uptake or AMPK signaling. PMID:20203065

  14. Contribution of propionate to glucose synthesis in sheep

    PubMed Central

    Leng, R. A.; Steel, J. W.; Luick, J. R.

    1967-01-01

    1. The production rate of propionate in the rumen and the entry rate of glucose into the body pool of glucose in sheep were measured by isotope-dilution methods. Propionate production rates were measured by using a continuous infusion of specifically labelled [14C]propionate. Glucose entry rates were estimated by using either a primed infusion or a continuous infusion of [U-14C]glucose. 2. The specific radioactivity of plasma glucose was constant between 4 and 9hr. after the commencement of intravenous infusion of [U-14C]glucose and between 1 and 3hr. when a primed infusion was used. 3. Infusion of [14C]propionate intraruminally resulted in a fairly constant specific radioactivity of rumen propionate between about 4 and 9hr. and of plasma glucose between 6 and 9hr. after the commencement of the infusion. Comparison of the mean specific radioactivities of glucose and propionate during these periods allowed estimates to be made of the contribution of propionate to glucose synthesis. 4. Comparisons of the specific radioactivities of plasma glucose and rumen propionate during intraruminal infusions of one of [1-14C]-, [2-14C]-, [3-14C]- and [U-14C]-propionate indicated considerable exchange of C-1 of propionate on conversion into glucose. The incorporation of C-2 and C-3 of propionate into glucose and lactate indicated that 54% of both the glucose and lactate synthesized arose from propionate carbon. 5. No differences were found for glucose entry rates measured either by a primed infusion or by a continuous infusion. The mean entry rate (±s.e.m.) of glucose estimated by using a continuous infusion into sheep was 0·33±0·03 (4) m-mole/min. and by using a primed infusion was 0·32±0·01 (4) m-mole/min. The mean propionate production rate was 1·24±0·03 (8) m-moles/min. The conversion of propionate into glucose was 0·36 m-mole/min., indicating that 32% of the propionate produced in the rumen is used for glucose synthesis. 6. It was indicated that a considerable

  15. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    PubMed

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia. PMID:27319094

  16. Glucose regulates lipid metabolism in fasting king penguins.

    PubMed

    Bernard, Servane F; Orvoine, Jord; Groscolas, René

    2003-08-01

    This study aims to determine whether glucose intervenes in the regulation of lipid metabolism in long-term fasting birds, using the king penguin as an animal model. Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo before, during, and after a 2-h glucose infusion under field conditions. All the birds were in the phase II fasting status (large fat stores, protein sparing) but differed by their metabolic and hormonal statuses, being either nonstressed (NSB; n = 5) or stressed (SB; n = 5). In both groups, glucose infusion at 5 mg.kg-1.min-1 induced a twofold increase in glycemia. In NSB, glucose had no effect on lipolysis (maintenance of plasma concentrations and rates of appearance of glycerol and nonesterified fatty acids) and no effect on the plasma concentrations of triacylglycerols (TAG), glucagon, insulin, or corticosterone. However, it limited fatty acid (FA) oxidation, as indicated by a 25% decrease in the plasma level of beta-hydroxybutyrate (beta-OHB). In SB, glucose infusion induced an approximately 2.5-fold decrease in lipolytic fluxes and a large decrease in FA oxidation, as reflected by a 64% decrease in the plasma concentration of beta-OHB. There were also a 35% decrease in plasma TAG, a 6.5- and 2.8-fold decrease in plasma glucagon and corticosterone, respectively, and a threefold increase in insulinemia. These data show that in fasting king penguins, glucose regulates lipid metabolism (inhibition of lipolysis and/or of FA oxidation) and affects hormonal status differently in stressed vs. nonstressed individuals. The results also suggest that in birds, as in humans, the availability of glucose, not of FA, is an important determinant of the substrate mix (glucose vs. FA) that is oxidized for energy production. PMID:12738609

  17. Identification and quantification of the main organic components of vinegars by high resolution 1H NMR spectroscopy.

    PubMed

    Caligiani, A; Acquotti, D; Palla, G; Bocchi, V

    2007-02-28

    A detailed analysis of the proton high-field NMR spectra of vinegars (in particular of Italian balsamic vinegars) is reported. A large number of organic substances belonging to different classes, such as carbohydrates, alcohols, organic acids, volatile compounds and amino acids, were assigned. The possibility of quantification of the substances identified in the whole vinegar sample, without extraction or pre-concentration steps, was also tested. The data validity was demonstrated in terms of precision, accuracy, repeatability and inter-day reproducibility. The effects of the most critical experimental parameters (sample concentration, water suppression and relaxation time) on the analysis response were also discussed. (1)H NMR results were compared with those obtained by traditional techniques (GC-MS, titrations), and good correlations were obtained. The results showed that (1)H NMR with water suppression allows a rapid, simultaneous determination of carbohydrates (glucose and fructose), organic acids (acetic, formic, lactic, malic, citric, succinic and tartaric acids), alcohols and polyols (ethanol, acetoin, 2,3-butanediol, hydroxymethylfurfural), and volatile substances (ethyl acetate) in vinegar samples. On the contrary, the amino acid determination without sample pre-concentration was critical. The (1)H NMR method proposed was applied to different samples of vinegars, allowing, in particular, the discrimination of vinegars and balsamic vinegars. PMID:17386654

  18. Vigorous exercise increases brain lactate and Glx (glutamate+glutamine): a dynamic 1H-MRS study.

    PubMed

    Maddock, Richard J; Casazza, Gretchen A; Buonocore, Michael H; Tanase, Costin

    2011-08-15

    Vigorous exercise increases lactate and glucose uptake by the brain in excess of the increase in brain oxygen uptake. The metabolic fate of this non-oxidized carbohydrate entering the brain is poorly understood, but accumulation of lactate in the brain and/or increased net synthesis of amino acid neurotransmitters are possible explanations. Previous proton magnetic resonance spectroscopy (1H-MRS) studies using conventional pulse sequences have not detected changes in brain lactate following exercise. This contrasts with 1H-MRS studies showing increased brain lactate when blood lactate levels are raised by an intravenous infusion of sodium lactate. Using a J-editing 1H-MRS technique for measuring lactate, we demonstrated a significant 19% increase in lactate in the visual cortex following graded exercise to approximately 85% of predicted maximum heart rate. However, the magnitude of the increase was insufficient to account for more than a small fraction of the non-oxidized carbohydrate entering the brain with exercise. We also report a significant 18% increase in Glx (combined signal from glutamate and glutamine) in visual cortex following exercise, which may represent an activity-dependent increase in glutamate. Future studies will be necessary to test the hypothesis that non-oxidized carbohydrate entering the brain during vigorous exercise is directed, in part, toward increased net synthesis of amino acid neurotransmitters. The possible relevance of these findings to panic disorder and major depression is discussed. PMID:21640838

  19. Metabolomics in Lung Inflammation: A High Resolution 1H NMR Study of Mice Exposed to Silica Dust

    PubMed Central

    Hu, Jian Zhi; Rommereim, Donald N.; Minard, Kevin R.; Woodstock, Angie; Harrer, Bruce J.; Wind, Robert A.; Phipps, Richard P.; Sime, Patricia J.

    2010-01-01

    Here we report the first 1H NMR metabolomics studies on excised lungs and bronchoalveolar lavage fluid (BALF) from mice exposed to crystalline silica. High resolution 1H NMR metabolic profiling on intact excised lungs was performed using slow magic angle sample spinning (slow-MAS) 1H PASS (phase altered spinning sidebands) at a sample spinning rate of 80 Hz. Metabolic profiling on BALF was completed using fast magic angle spinning at 2kHz. Major findings are that the relative concentrations of choline, phosphocholine (PC) and glycerophosphocholine(GPC) were statistically significantly increased in silica-exposed mice compared to sham controls, indicating an altered membrane choline phospholipids metabolism (MCPM). The relative concentrations of glycogen/glucose, lactate and creatine were also statistically significantly increased in mice exposed to silica dust, suggesting that cellular energy pathways were affected by silica dust. Elevated levels of glycine, lysine, glutamate, proline and 4-hydroxyproline were also increased in exposed mice, suggesting the activation of a collagen pathway. Furthermore, metabolic profiles in mice exposed to silica dust were found to be spatially heterogeneous, in consistent with regional inflammation revealed by in vivo magnetic resonance imaging (MRI). PMID:20020862

  20. Evaluation of the appropriateness of using glucometers for measuring the blood glucose levels in mice.

    PubMed

    Togashi, Yu; Shirakawa, Jun; Okuyama, Tomoko; Yamazaki, Shunsuke; Kyohara, Mayu; Miyazawa, Ayumi; Suzuki, Takafumi; Hamada, Mari; Terauchi, Yasuo

    2016-01-01

    Glucometers are also widely used in diabetes research conducted using animal models. However, the appropriateness of measuring blood glucose levels using glucometers in animal models remains unclear. In this study, we evaluated the consistency between the blood glucose levels measured by 11 models of glucometers and plasma glucose levels measured by a laboratory biochemical test in blood samples collected by retro-orbital sinus puncture or tail-tip amputation. In both blood samples obtained by retro-orbital sinus puncture and those obtained by tail-tip amputation, 10 of the 11 models of glucometers yielded higher glucose values, while 1 yielded lower glucose values, than the plasma glucose values yielded by the laboratory test, the differences being in direct proportion to the plasma glucose values. Most glucometers recorded higher blood glucose levels after glucose loading and lower blood glucose levels after insulin loading in retro-orbital sinus blood as compared to tail vein blood. Our data suggest that the blood glucose levels measured by glucometers in mice tended to be higher than the plasma glucose levels yielded by the biochemical test under the hyperglycemic state, and that differences in the measured levels were observed according to the blood collection method depending on the glycemia status. PMID:27151424

  1. Evaluation of the appropriateness of using glucometers for measuring the blood glucose levels in mice

    PubMed Central

    Togashi, Yu; Shirakawa, Jun; Okuyama, Tomoko; Yamazaki, Shunsuke; Kyohara, Mayu; Miyazawa, Ayumi; Suzuki, Takafumi; Hamada, Mari; Terauchi, Yasuo

    2016-01-01

    Glucometers are also widely used in diabetes research conducted using animal models. However, the appropriateness of measuring blood glucose levels using glucometers in animal models remains unclear. In this study, we evaluated the consistency between the blood glucose levels measured by 11 models of glucometers and plasma glucose levels measured by a laboratory biochemical test in blood samples collected by retro-orbital sinus puncture or tail-tip amputation. In both blood samples obtained by retro-orbital sinus puncture and those obtained by tail-tip amputation, 10 of the 11 models of glucometers yielded higher glucose values, while 1 yielded lower glucose values, than the plasma glucose values yielded by the laboratory test, the differences being in direct proportion to the plasma glucose values. Most glucometers recorded higher blood glucose levels after glucose loading and lower blood glucose levels after insulin loading in retro-orbital sinus blood as compared to tail vein blood. Our data suggest that the blood glucose levels measured by glucometers in mice tended to be higher than the plasma glucose levels yielded by the biochemical test under the hyperglycemic state, and that differences in the measured levels were observed according to the blood collection method depending on the glycemia status. PMID:27151424

  2. Mechanisms to conserve glucose in lactating women during a 42-h fast

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about how lactating women accommodate for their increased glucose demands during fasting to avoid maternal hypoglycemia. The objective of this study was to determine whether lactating women conserve plasma glucose by reducing maternal glucose utilization by increasing utilization of ...

  3. Pulmonary glucose transport in the fetal sheep.

    PubMed Central

    Barker, P M; Boyd, C A; Ramsden, C A; Strang, L B; Walters, D V

    1989-01-01

    1. In the chronically catheterized sheep fetus between 122 and 143 days gestation the concentration of D-glucose in lung liquid was very low (usually less than 0.01 mM, the lower limit of detection of the analytical method) whereas the mean plasma concentration was 0.19 mM (S.E.M. 0.4, n = 13). 2. When the lung liquid concentration of D-glucose was raised to 1.67-5.00 mM, rapid uptake was observed until the concentration had fallen to its preceding low level. The uptake showed saturation kinetics (Vmax = 2.29-8.78 mumol/min, increasing with gestation; mean Km = 0.14 +/- 0.02 mM, n = 11, no change with gestation). This active uptake of glucose was blocked by phloridzin (10(-4) M). It was associated with a decrease in lung liquid secretion rate from which a change in net sodium flux could be inferred of an order suggesting one-to-one glucose-sodium co-transport. 3. Radiolabelled 3-O-methyl-D-glucose (3-O-meG) - a monosaccharide which is transported but not metabolized - was taken up rapidly from lung liquid and this rapid uptake was inhibited by D-glucose with 50% inhibition at 0.35 mM (+/- 0.08, n = 9). It was also inhibited by phloridzin (10(-4) M). 4. Radiolabelled 2-deoxy-D-glucose - a monosaccharide which is not a substrate for sodium-coupled transport - was taken up only very slowly from lung liquid; the rate of uptake was appropriate for passive diffusional transport and it was unaffected by the addition of D-glucose or phloridzin to lung liquid. 5. Intravenous infusion of D-glucose caused no detectable increase in the concentration of glucose in lung liquid unless phloridzin was added, when a slow increase was observed. 6. In two experiments with active transport blocked by phloridzin in lung liquid (10(-4) M), the rate of entry of labelled 3-O-meG from plasma to lung liquid was measured during intravenous infusion of this tracer for 29 and 23 h. The rates of entry were similar to the rate of efflux of the tracer from lung liquid when uptake was blocked by

  4. Intra- and extracellular carbohydrates in plant cell cultures investigated by (1)H-NMR.

    PubMed

    Schripsema, J; Erkelens, C; Verpoorte, R

    1991-01-01

    With the aim of quantifying intra- and extracellular carbohydrates media and cell-extracts from a Tabernaemontana divaricata plant cell-suspension culture were investigated with (1)H-NMR.For suppression of the solvent peak the Meiboom-Gill modification of the Carr-Purcell (CPMG) spin-echo sequence was used after addition of a paramagnetic relaxation agent (Mn(2+)) to the sample. Several aspects of this method were optimized (the manganese concentration, the interpulse delay and the number of spin-echo cycles) so as to obtain a rapid and easy method in which no pretreatment of media or cell-extracts was needed. Besides the speed and ease of the method, also the direct identification of carbohydrates and other main components is an advantage.The exhaustion of extracellular carbohydrates was found to coincide with the maximum amount of intracellular carbohydrates. The intracellular carbohydrates, i.e. glucose and fructose, were consumed at a low rate, during several weeks. PMID:24213796

  5. {sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

    SciTech Connect

    Zhang, Ying; Lin, Lianjie; Xu, Yanbin; Lin, Yan; Jin, Yu; Zheng, Changqing

    2013-04-19

    Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected to multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.

  6. Metabolic profile of the hippocampus of Zucker Diabetic Fatty rats assessed by in vivo 1H magnetic resonance spectroscopy.

    PubMed

    van der Graaf, Marinette; Janssen, Susan W J; van Asten, Jack J A; Hermus, Ad R M M; Sweep, C G J; Pikkemaat, Jeroen A; Martens, Gerard J M; Heerschap, Arend

    2004-10-01

    Localized in vivo 1H magnetic resonance spectroscopy (MRS) was used to investigate metabolite levels in the brain of adult Zucker Diabetic Fatty (ZDF) rats, an animal model for type 2 diabetes mellitus. This study focussed on the hippocampus, assumed to be one of the main brain areas affected by this disease. Together with an almost 5-fold increase in blood glucose concentration measured by glucose oxidation, significant increases were found in the hippocampal concentrations of glucose (4.93 vs 1.66 mM p < 0.001), myo-inositol (6.52 vs 4.30 mM; p < 0.05), and total creatine (12.71 vs 10.50 mM; p < 0.05) in ZDF rats (n = 5) compared with littermates (n = 5). Although no obvious alterations were detected in the hippocampal levels of other metabolites, including NAA + NAAG and choline-containing compounds in the ZDF rats, the increase in Glc and Ins levels is in line with elevated brain tissue contents of these metabolites in patients with diabetes mellitus. PMID:15386626

  7. Hourly analysis of cerebrospinal fluid glucose shows large diurnal fluctuations.

    PubMed

    Verbeek, Marcel M; Leen, Wilhelmina G; Willemsen, Michèl A; Slats, Diane; Claassen, Jurgen A

    2016-05-01

    Cerebrospinal fluid analysis is important in the diagnostics of many neurological disorders. Since the influence of food intake on the cerebrospinal fluid glucose concentration and the cerebrospinal fluid/plasma glucose ratio is largely unknown, we studied fluctuations in these parameters in healthy adult volunteers during a period of 36 h. Our observations show large physiological fluctuations of cerebrospinal fluid glucose and the cerebrospinal fluid/plasma glucose ratio, and their relation to food intake. These findings provide novel insights into the physiology of cerebral processes dependent on glucose levels such as energy formation (e.g. glycolysis), enzymatic reactions (e.g. glycosylation), and non-enzymatic reactions (e.g. advanced endproduct glycation). PMID:26945018

  8. The modulatory role of spinally located histamine receptors in the regulation of the blood glucose level in d-glucose-fed mice.

    PubMed

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

    2014-02-01

    The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model. PMID:24634595

  9. Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

    PubMed

    Tamboli, Robyn A; Sidani, Reem M; Garcia, Anna E; Antoun, Joseph; Isbell, James M; Albaugh, Vance L; Abumrad, Naji N

    2016-07-01

    Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion. PMID:27279247

  10. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression.

    PubMed Central

    Kahn, B B; Shulman, G I; DeFronzo, R A; Cushman, S W; Rossetti, L

    1991-01-01

    Evidence is emerging for a direct role of glucose, independent of changes in insulin, in the regulation of cellular glucose transport and glucose utilization in vivo. In this study we investigate potential cellular and molecular mechanisms for this regulatory effect of glucose by determining how normalization of glycemia without insulin therapy in diabetic rats influences 3-O-methylglucose transport and the expression and translocation of two genetically distinct species of glucose transporters (GTs) in adipose cells. These results are compared with alterations in glucose disposal in vivo measured by euglycemic clamp. In rats rendered diabetic by 90% pancreatectomy, insulin-stimulated glucose transport in adipose cells is decreased 50% in parallel with reduced insulin-mediated glucose disposal in vivo. Levels of adipose/muscle GTs measured by immunoblotting are decreased in adipose cell subcellular membrane fractions, as are the corresponding mRNA levels assessed by Northern blotting of total adipose cell RNA. Normalization of blood glucose in diabetic rats with phlorizin, which impairs renal tubular glucose reabsorption and thus enhances glucose excretion, restores insulin-stimulated glucose transport in adipose cells and insulin-mediated glucose disposal in vivo. Importantly, levels of the adipose/muscle GT protein remain 43% reduced in the low-density microsomes in the basal state and 46% reduced in the plasma membranes in the insulin-stimulated state. Adipose/muscle GT mRNA levels remain approximately 50% depressed. Levels of the HepG2/brain GT protein and mRNA are unaltered by diabetes or phlorizin treatment. Thus, changes in ambient glucose independent of changes in ambient insulin can regulate the glucose transport response to insulin in isolated adipose cells and changes in responsiveness parallel alterations in glucose uptake in vivo. Since this effect can occur without alteration in the expression of the two species of glucose transporters present in

  11. 1H NMR metabolomics study of age profiling in children

    PubMed Central

    Gu, Haiwei; Pan, Zhengzheng; Xi, Bowei; Hainline, Bryan E.; Shanaiah, Narasimhamurthy; Asiago, Vincent; Nagana Gowda, G. A.; Raftery, Daniel

    2014-01-01

    Metabolic profiling of urine provides a fingerprint of personalized endogenous metabolite markers that correlate to a number of factors such as gender, disease, diet, toxicity, medication, and age. It is important to study these factors individually, if possible to unravel their unique contributions. In this study, age-related metabolic changes in children of age 12 years and below were analyzed by 1H NMR spectroscopy of urine. The effect of age on the urinary metabolite profile was observed as a distinct age-dependent clustering even from the unsupervised principal component analysis. Further analysis, using partial least squares with orthogonal signal correction regression with respect to age, resulted in the identification of an age-related metabolic profile. Metabolites that correlated with age included creatinine, creatine, glycine, betaine/TMAO, citrate, succinate, and acetone. Although creatinine increased with age, all the other metabolites decreased. These results may be potentially useful in assessing the biological age (as opposed to chronological) of young humans as well as in providing a deeper understanding of the confounding factors in the application of metabolomics. PMID:19441074

  12. Preliminary 1H NMR study on archaeological waterlogged wood.

    PubMed

    Maccotta, Antonella; Fantazzini, Paola; Garavaglia, Carla; Donato, Ines D; Perzia, Patrizia; Brai, Maria; Morreale, Filippa

    2005-01-01

    Magnetic Resonance Relaxation (MRR) and Magnetic Resonance Imaging (MRI) are powerful tools to obtain detailed information on the pore space structure that one is unlikely to obtain in other ways. These techniques are particularly suitable for Cultural Heritage materials, because they use water 1H nuclei as a probe. Interaction with water is one of the main causes of deterioration of materials. Porous structure in wood, for example, favours the penetration of water, which can carry polluting substances and promote mould growth. A particular case is waterlogged wood from underwater discoveries and moist sites; in fact, these finds are very fragile because of chemical, physical and biological decay from the long contact with the water. When wood artefacts are brought to the surface and directly dried in air, there is the collapse of the cellular structures, and wood loses its original form and dimensions and cannot be used for study and museum exhibits. In this work we have undertaken the study of some wood finds coming from Ercolano's harbour by MRR and MRI under different conditions, and we have obtained a characterization of pore space in wood and images of the spatial distribution of the confined water in the wood. PMID:16485652

  13. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, K.N.; Xu, J.

    1997-04-29

    Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

  14. The Conformations and Structures of 1H-NONAFLUOROBUTANE

    NASA Astrophysics Data System (ADS)

    Fournier, Joseph A.; Bohn, Robert K.; Montgomery, John A.; , Jr.

    2012-06-01

    The all trans conformers of perfluorocarbons, unlike hydrocarbons, are helical with C-C-C-C dihedral angles about 1640. Fluorocarbons with H substitution can replace chlorofluorocarbons as propellants and compressor fluids without the disadvantage of causing ozone depletion in the upper atmosphere. 1H-perfluorobutane, CHF_2CF_2CF_2CF_3, has been studied by pulsed-jet Fourier transform microwave spectroscopy. The spectrum is very rich. Quantum chemical calculations identify five stable conformers with relative energies up to 1.1 kcal/mol. Thus far three conformers have been characterized and many lines remain unassigned. The assigned species have CCCCanti/CCCH gauche as well as the anti/anti and gauche/anti forms. Rotational constant values are 1428.9501(2) MHz, 593.323877(6) MHz, and 546.43578(6) MHz for the anti/gauche species, 1323.664(3) MHz, 617.6051(5) MHz for the ant/anti species, and 1066.9384(4) MHz, 768.4736(4) MHz, and 671.3145(4) MHz for the gauche/anti form.

  15. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, Kenneth N.; Xu, Jide

    1997-01-01

    Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

  16. 1H NMR Metabolomics Analysis of Glioblastoma Subtypes

    PubMed Central

    Cuperlovic-Culf, Miroslava; Ferguson, Dean; Culf, Adrian; Morin, Pier; Touaibia, Mohamed

    2012-01-01

    Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by unpredictable clinical behaviors that suggest distinct molecular subtypes. With the tumor metabolic phenotype being one of the hallmarks of cancer, we have set upon to investigate whether GBMs show differences in their metabolic profiles. 1H NMR analysis was performed on metabolite extracts from a selection of nine glioblastoma cell lines. Analysis was performed directly on spectral data and on relative concentrations of metabolites obtained from spectra using a multivariate regression method developed in this work. Both qualitative and quantitative sample clustering have shown that cell lines can be divided into four groups for which the most significantly different metabolites have been determined. Analysis shows that some of the major cancer metabolic markers (such as choline, lactate, and glutamine) have significantly dissimilar concentrations in different GBM groups. The obtained lists of metabolic markers for subgroups were correlated with gene expression data for the same cell lines. Metabolic analysis generally agrees with gene expression measurements, and in several cases, we have shown in detail how the metabolic results can be correlated with the analysis of gene expression. Combined gene expression and metabolomics analysis have shown differential expression of transporters of metabolic markers in these cells as well as some of the major metabolic pathways leading to accumulation of metabolites. Obtained lists of marker metabolites can be leveraged for subtype determination in glioblastomas. PMID:22528487

  17. Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism

    PubMed Central

    König, Matthias; Bulik, Sascha; Holzhütter, Hermann-Georg

    2012-01-01

    Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical model of human hepatic glucose metabolism is lacking so far. Here we present a detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of these pathways by insulin, glucagon and epinephrine. Model simulations are in good agreement with experimental data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization under varying physiological states. (ii) the time courses of postprandial glycogen storage as well as glycogen depletion in overnight fasting and short term fasting (iii) the switch from net hepatic glucose production under hypoglycemia to net hepatic glucose utilization under hyperglycemia essential for glucose homeostasis (iv) hormone perturbations of hepatic glucose metabolism. Response analysis reveals an extra high capacity of the liver to counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above 7.5 mM (hyperglycemia). Our model may serve as an important module of a whole-body model of human glucose metabolism and as a valuable tool for understanding the role of the liver in glucose homeostasis under normal conditions and in diseases like diabetes or glycogen storage diseases. PMID:22761565

  18. Toxicometabolomics approach to urinary biomarkers for mercuric chloride (HgCl{sub 2})-induced nephrotoxicity using proton nuclear magnetic resonance ({sup 1}H NMR) in rats

    SciTech Connect

    Kim, Kyu-Bong; Um, So Young; Chung, Myeon Woo; Jung, Seung Chul; Oh, Ji Seon; Kim, Seon Hwa; Na, Han Sung; Lee, Byung Mu; Choi, Ki Hwan

    2010-12-01

    The primary objective of this study was to determine and characterize surrogate biomarkers that can predict nephrotoxicity induced by mercuric chloride (HgCl{sub 2}) using urinary proton nuclear magnetic resonance ({sup 1}H NMR) spectral data. A procedure for {sup 1}H NMR urinalysis using pattern recognition was proposed to evaluate nephrotoxicity induced by HgCl{sub 2} in Sprague-Dawley rats. HgCl{sub 2} at 0.1 or 0.75 mg/kg was administered intraperitoneally (i.p.), and urine was collected every 24 h for 6 days. Animals (n = 6 per group) were sacrificed 3 or 6 days post-dosing in order to perform clinical blood chemistry tests and histopathologic examinations. Urinary {sup 1}H NMR spectroscopy revealed apparent differential clustering between the control and HgCl{sub 2} treatment groups as evidenced by principal component analysis (PCA) and partial least square (PLS)-discriminant analysis (DA). Time- and dose-dependent separation of HgCl{sub 2}-treated animals from controls was observed by PCA of {sup 1}H NMR spectral data. In HgCl{sub 2}-treated rats, the concentrations of endogenous urinary metabolites of glucose, acetate, alanine, lactate, succinate, and ethanol were significantly increased, whereas the concentrations of 2-oxoglutarate, allantoin, citrate, formate, taurine, and hippurate were significantly decreased. These endogenous metabolites were selected as putative biomarkers for HgCl{sub 2}-induced nephrotoxicity. A dose response was observed in concentrations of lactate, acetate, succinate, and ethanol, where severe disruption of the concentrations of 2-oxoglutarate, citrate, formate, glucose, and taurine was observed at the higher dose (0.75 mg/kg) of HgCl{sub 2}. Correlation of urinary {sup 1}H NMR PLS-DA data with renal histopathologic changes suggests that {sup 1}H NMR urinalysis can be used to predict or screen for HgCl{sub 2}-induced nephrotoxicity{sub .}

  19. 1H NMR Spectroscopy and MVA Analysis of Diplodus sargus Eating the Exotic Pest Caulerpa cylindracea

    PubMed Central

    De Pascali, Sandra A.; Del Coco, Laura; Felline, Serena; Mollo, Ernesto; Terlizzi, Antonio; Fanizzi, Francesco P.

    2015-01-01

    The green alga Caulerpa cylindracea is a non-autochthonous and invasive species that is severely affecting the native communities in the Mediterranean Sea. Recent researches show that the native edible fish Diplodus sargus actively feeds on this alga and cellular and physiological alterations have been related to the novel alimentary habits. The complex effects of such a trophic exposure to the invasive pest are still poorly understood. Here we report on the metabolic profiles of plasma from D. sargus individuals exposed to C. cylindracea along the southern Italian coast, using 1H NMR spectroscopy and multivariate analysis (Principal Component Analysis, PCA, Orthogonal Partial Least Square, PLS, and Orthogonal Partial Least Square Discriminant Analysis, OPLS-DA). Fish were sampled in two seasonal periods from three different locations, each characterized by a different degree of algal abundance. The levels of the algal bisindole alkaloid caulerpin, which is accumulated in the fish tissues, was used as an indicator of the trophic exposure to the seaweed and related to the plasma metabolic profiles. The profiles appeared clearly influenced by the sampling period beside the content of caulerpin, while the analyses also supported a moderate alteration of lipid and choline metabolism related to the Caulerpa-based diet. PMID:26058009

  20. Effects of high fructose and salt feeding on systematic metabonome probed via (1) H NMR spectroscopy.

    PubMed

    Yang, Yongxia; Zheng, Lingyun; Wang, Linlin; Wang, Shumei; Wang, Yaling; Han, Zhihui

    2015-04-01

    Diets rich in high fructose and salt are increasingly popular in our daily life. A combination consumption of excessive fructose and salt can induce insulin resistance (IR) and hypertension (HT), which are major public health problems around the world. However, the effects of high fructose and salt on systematic metabonome remain unknown, which is very important for revealing the molecular mechanism of IR and HT induced by this dietary pattern. The metabolic profiling in urine, plasma, and fecal extracts from high fructose and salt-fed rats was investigated by use of (1) H nuclear magnetic resonance (NMR)-based metabonomics approach in this study. Multivariate analysis of NMR data showed the effects of high fructose and salt on the global metabonome. The metabolite analysis in urine and fecal extracts showed the time-dependent metabolic changes, which displayed metabonomic progression axes from normal to IR and HT status. The changes of 2-oxoglutarate, creatine and creatinine, citrate, hippurate, trimethylamine N-oxide (TMAO), and betaine in urine, together with gut microbiota disorder in feces, were observed at the preliminary formation stage of IR and HT (fourth week). At the severe stage (eighth week), the previously mentioned metabolic changes were aggravated, and the changes of lipid and choline metabolism in plasma suggested the increased risk of cardiovascular diseases. These findings provide an overview of biochemistry consequences of high fructose and salt feeding and comprehensive insights into the progression of systematic metabonome for IR and HT induced by this dietary pattern. PMID:25641270

  1. 1H NMR Spectroscopy and MVA Analysis of Diplodus sargus Eating the Exotic Pest Caulerpa cylindracea.

    PubMed

    De Pascali, Sandra A; Del Coco, Laura; Felline, Serena; Mollo, Ernesto; Terlizzi, Antonio; Fanizzi, Francesco P

    2015-06-01

    The green alga Caulerpa cylindracea is a non-autochthonous and invasive species that is severely affecting the native communities in the Mediterranean Sea. Recent researches show that the native edible fish Diplodus sargus actively feeds on this alga and cellular and physiological alterations have been related to the novel alimentary habits. The complex effects of such a trophic exposure to the invasive pest are still poorly understood. Here we report on the metabolic profiles of plasma from D. sargus individuals exposed to C. cylindracea along the southern Italian coast, using 1H NMR spectroscopy and multivariate analysis (Principal Component Analysis, PCA, Orthogonal Partial Least Square, PLS, and Orthogonal Partial Least Square Discriminant Analysis, OPLS-DA). Fish were sampled in two seasonal periods from three different locations, each characterized by a different degree of algal abundance. The levels of the algal bisindole alkaloid caulerpin, which is accumulated in the fish tissues, was used as an indicator of the trophic exposure to the seaweed and related to the plasma metabolic profiles. The profiles appeared clearly influenced by the sampling period beside the content of caulerpin, while the analyses also supported a moderate alteration of lipid and choline metabolism related to the Caulerpa-based diet. PMID:26058009

  2. Okara ameliorates glucose tolerance in GK rats

    PubMed Central

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-01-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  3. Okara ameliorates glucose tolerance in GK rats.

    PubMed

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-05-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  4. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    SciTech Connect

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  5. Analysis of plasma metabolic biomarkers in the development of 4-nitroquinoline-1-oxide-induced oral carcinogenesis in rats

    PubMed Central

    KONG, XIANGLI; YANG, XIAOQIN; ZHOU, JINGLIN; CHEN, SIXIU; LI, XIAOYU; JIAN, FAN; DENG, PENGCHI; LI, WEI

    2015-01-01

    The aim of the present study was to identify time-dependent changes in the expression of metabolic biomarkers during the various stages of oral carcinogenesis to provide an insight into the sequential mechanism of oral cancer development. An 1H nuclear magnetic resonance (NMR)-based metabolomics approach was used to analyze the blood plasma samples of Sprague-Dawley rats exhibiting various oral lesions induced by the administration of 4-nitroquinoline-1-oxide (4NQO) in drinking water. The 1H NMR spectra were processed by principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) to determine the metabolic differences between the three developmental stages of oral mucosa cancer (health, oral leukoplakia [OLK] and oral squamous cell carcinoma [OSCC]). The variable importance in projection (VIP) score derived from the PLS-DA model was used to screen for important metabolites, whose significance was further verified through analysis of variance (ANOVA). Data from the present study indicated that 4NQO-induced rat oral carcinogenesis produced oral pre-neoplastic and neoplastic lesions and provided an effective model for analyzing sequential changes in the 1H NMR spectra of rat blood plasma. The 1H NMR-based metabolomics approach clearly differentiates between healthy, OLK and OSSC rats in the PCA and PLS-DA models. Furthermore, lactic acid, choline, glucose, proline, valine, isoleucine, aspartic acid and 2-hydroxybutyric acid demonstrated VIP>1 in the PLS-D model and P<0.05 with ANOVA. It was also identified that increases in lactic acid, choline and glucose, and decreases in proline, valine, isoleucine, aspartic acid and 2-hydroxybutyric acid may be relative to the characteristic mechanisms of oral carcinogenesis. Therefore, these plasma metabolites may serve as metabolic biomarkers in oral carcinogenesis and assist in the early diagnosis and preventive treatment of oral cancer. PMID:25435976

  6. Imaging the Tissue Distribution of Glucose in Livers Using A PARACEST Sensor

    PubMed Central

    Ren, Jimin; Trokowski, Robert; Zhang, Shanrong; Malloy, Craig R.; Sherry, A. Dean

    2009-01-01

    Noninvasive imaging of glucose in tissues could provide important insights about glucose gradients in tissue, the origins of gluconeogenesis, or perhaps differences in tissue glucose utilization in vivo. Direct spectral detection of glucose in vivo by 1H NMR is complicated by interfering signals from other metabolites and the much larger water signal. One potential way to overcome these problems is to use an exogenous glucose sensor that reports glucose concentrations indirectly through the water signal by chemical exchange saturation transfer (CEST). Such a method is demonstrated here in mouse liver perfused with a Eu3+-based glucose sensor containing two phenylboronate moieties as the recognition site. Activation of the sensor by applying a frequency-selective presaturation pulse at 42 ppm resulted in a 17% decrease in water signal in livers perfused with 10 mM sensor and 10 mM glucose compared with livers with the same amount of sensor but without glucose. It was shown that livers perfused with 5 mM sensor but no glucose can detect glucose exported from hepatocytes after hormonal stimulation of glycogenolysis. CEST images of livers perfused in the magnet responded to changes in glucose concentrations demonstrating that the method has potential for imaging the tissue distribution of glucose in vivo. PMID:18958853

  7. Effect of anesthesia on glucose production and utilization in rats

    SciTech Connect

    Penicaud, L.; Ferre, P.; Kande, J.; Leturque, A.; Issad, T.; Girard, J.

    1987-03-01

    This study was undertaken to determine the effects of pentobarbital anesthesia (50 mg/kg ip) on glucose kinetics and individual tissue glucose utilization in vivo, in chronically catheterized rats. Glucose turnover studies were carried out using (3-/sup 3/H) glucose as tracer. A transient hyperglycemia and an increased glucose production were observed 3 min after induction of anesthesia. However, 40 min after induction of anesthesia, glycemia returned to the level observed in awake animals, whereas glucose turnover was decreased by 30% as compared with unanesthetized rats. These results are discussed with regard to the variations observed in plasma insulin, glucagon, and catecholamine levels. Glucose utilization by individual tissues was studied by the 2-(1-/sup 3/H) deoxyglucose technique. A four- to fivefold decrease in glucose utilization was observed in postural muscles (soleus and adductor longus), while in other nonpostural muscles (epitrochlearis, tibialis anterior, extensor digitorum longus, and diaphragm) and other tissues (white and brown adipose tissues) anesthesia did not modify the rate of glucose utilization. A decrease in glucose utilization was also observed in the brain.

  8. Glucose: detection and analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glucose is an aldosic monosaccharide that is centrally entrenched in the processes of photosynthesis and respiration, serving as an energy reserve and metabolic fuel in most organisms. As both a monomer and as part of more complex structures such as polysaccharides and glucosides, glucose also pla...

  9. Monitor blood glucose - slideshow

    MedlinePlus

    ... medlineplus.gov/ency/presentations/100220.htm Monitoring blood glucose - Series—Monitoring blood glucose: Using a self-test meter To use the ... A.M. Editorial team. Related MedlinePlus Health Topics Blood Sugar A.D.A.M., Inc. is accredited by ...

  10. Glucose monitoring during Ramadan.

    PubMed

    Jabbar, Abdul

    2015-05-01

    In patients with diabetes who intend to fast during Ramadan, self-monitoring of blood glucose (SMBG) is an important tool. During this month, a long established treatment regimen, including medications, physical activity and diet plan, is changed to achieve concordance with the rules of fasting. Without proper glucose monitoring, it is not possible to achieve good glycaemic control. PMID:26013788

  11. Interference Reduction in Glucose Detection by Redox Potential Tuning: New Glucose Meter Development.

    PubMed

    Cho, Seong Je; Cho, Chul-Ho; Kim, Kwang Bok; Lee, Min-Hyoung; Kim, Jae Hong; Lee, Suho; Cho, Jaegeol; Jung, Suntae; Kim, Dong-Min; Shim, Yoon-Bo

    2015-01-01

    A new glucose meter was developed employing a novel disposable glucose sensor strip comprising a nicotinamide adenine dinucleotide-glucose dehydrogenase (NAD-GDH) and a mixture of Fe compounds as a mediator. An iron complex, 5-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)-1,10-phenanthroline iron(III) chloride (Fe-PhenTPy), was synthesized as a new mediator for the NAD-GDH system. Due to the high oxidation potential of the mediator, the detection potential was tuned to be more closely fitted toward the enzyme reaction potential, less than 400 mV (vs. Ag/AgCl), by mixing with an additional iron mediator. The impedance spectrometry for the enzyme sensor containing the mixed mediators showed an enhanced charge transfer property. In addition, a new cartridge-type glucose meter was manufactured using effective aligned-electrodes, which showed an enhanced response compared with conventional electrode alignment. The proposed glucose sensor resulted in a wide dynamic range in the concentration range of 30 - 500 mg dL(-1) with a reduced interference effect and a good sensitivity of 0.57 μA mM(-1). PMID:26165295

  12. Fermentation performance and structure characteristics of xanthan produced by Xanthomonas campestris with a glucose/xylose mixture.

    PubMed

    Zhang, Zhiguo; Chen, Hongzhang

    2010-03-01

    The ability of Xanthomonas campestris to convert glucose and xylose to xanthan and the structure of xanthan derived from the glucose/xylose mixture media are important when the lignocelluloses hydrolysate was used in xanthan production. In this paper, the features related to xanthan fermentation in the glucose/xylose mixture media and the structures of xanthan derived from the mixture media were studied. Glucose was the preferred carbon source to produce xanthan while xylose was also utilized with a very low consumption rate. When the fraction of glucose decreased from 100% to 25%, the glucose consumption rate and xanthan production rate reduced from 0.44 g L(-1) h(-1) to 0.25 g L(-1) h(-1) and 0.21 g L(-1) h(-1) to 0.04 g L(-1) h(-1) respectively while xylose was consumed at a very stable rate (0.053-0.060 g L(-1) h(-1)). On the other hand, when the xylose fraction increased from 0% to 50%, pyruvate and acetate content of xanthan increased from 2.43% to 3.78% and 2.55% to 7.05%. The existence of xylose also led to higher average molecular weight. Therefore, it could be concluded that xylose was not efficiently utilized by X. campestris to produce xanthan. The concentration of glucose rather than the total sugar was the main factor to determine the xanthan production. But xylose was helpful to improve the quality of xanthan. PMID:19459070

  13. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring.

    PubMed

    Ma, Ya-Hong; Yu, Caiguo; Kayoumu, Abudurexiti; Guo, Xin; Ji, Zhili; Liu, George

    2015-04-01

    Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring: maternal non-transgenic control and maternal transgenic offspring, and paternal control and paternal transgenic offspring. Plasma triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG) and fasting insulin (FINS) were measured. ApoCIII overexpression caused severe hypertriglyceridemia, but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups. The 4 groups of offspring had similar birth weight and growth rate. The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice, but there was no difference in plasma TG between maternal and paternal transgenic offspring. Although the FPG of the 4 groups of animals had no difference, the maternal transgenic mice showed impaired glucose tolerance, increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups. In conclusion, maternally inherited hypertriglyceridemia in ApoCIII transgenic mice displayed impaired glucose tolerance, hyperinsulinemia and increased HOMA-R, while paternally inherited hypertriglyceridemia did not have such impacts. PMID:25859267

  14. Drought Stress-Induced Rma1H1, a RING Membrane-Anchor E3 Ubiquitin Ligase Homolog, Regulates Aquaporin Levels via Ubiquitination in Transgenic Arabidopsis Plants[C][W

    PubMed Central

    Lee, Hyun Kyung; Cho, Seok Keun; Son, Ora; Xu, Zhengyi; Hwang, Inhwan; Kim, Woo Taek

    2009-01-01

    Ubiquitination is involved in a variety of biological processes, but the exact role of ubiquitination in abiotic responses is not clearly understood in higher plants. Here, we investigated Rma1H1, a hot pepper (Capsicum annuum) homolog of a human RING membrane-anchor 1 E3 ubiquitin (Ub) ligase. Bacterially expressed Rma1H1 displayed E3 Ub ligase activity in vitro. Rma1H1 was rapidly induced by various abiotic stresses, including dehydration, and its overexpression in transgenic Arabidopsis thaliana plants conferred strongly enhanced tolerance to drought stress. Colocalization experiments with marker proteins revealed that Rma1H1 resides in the endoplasmic reticulum (ER) membrane. Overexpression of Rma1H1 in Arabidopsis inhibited trafficking of an aquaporin isoform PIP2;1 from the ER to the plasma membrane and reduced PIP2;1 levels in protoplasts and transgenic plants. This Rma1H1-induced reduction of PIP2;1 was inhibited by MG132, an inhibitor of the 26S proteasome. Furthermore, Rma1H1 interacted with PIP2;1 in vitro and ubiquitinated it in vivo. Similar to Rma1H1, Rma1, an Arabidopsis homolog of Rma1H1, localized to the ER, and its overexpression reduced the PIP2;1 protein level and inhibited trafficking of PIP2;1 from the ER to the plasma membrane in protoplasts. In addition, reduced expression of Rma homologs resulted in the increased level of PIP2;1 in protoplasts. We propose that Rma1H1 and Rma1 play a critical role in the downregulation of plasma membrane aquaporin levels by inhibiting aquaporin trafficking to the plasma membrane and subsequent proteasomal degradation as a response to dehydration in transgenic Arabidopsis plants. PMID:19234086

  15. Comparison and Correlation of Glucose Levels in Serum and Saliva of Both Diabetic and Non-diabetic Patients

    PubMed Central

    Patel, Bhumika J; Dave, Bela; Dave, Dilip; Karmakar, Payel; Shah, Mona; Sarvaiya, Bhumi

    2015-01-01

    Background: To detect and compare salivary glucose with plasma glucose level and postprandial blood sugar (PPBS) and fasting blood sugar (FBS) in diabetic and non-diabetic subjects. Materials and Methods: A total of 100 patients were participated in this study. They were divided into two groups, each group consist of 50 patients. Un-stimulated saliva and blood were collected and investigated for glucose levels. Results: FBS, PPBS, plasma glucose levels and salivary glucose levels were higher in diabetic patients than healthy controls. FBS, PPBS, plasma glucose level and salivary glucose levels were significantly correlated with each other in diabetic patients Conclusion: Salivary glucose level can be used for monitoring tool to assess the glycemic status of diabetes mellitus patients as it is noninvasive and diagnostic method. PMID:26464543

  16. Automated data processing of { 1H-decoupled} 13C MR spectra acquired from human brain in vivo

    NASA Astrophysics Data System (ADS)

    Shic, Frederick; Ross, Brian

    2003-06-01

    In clinical 13C infusion studies, broadband excitation of 200 ppm of the human brain yields 13C MR spectra with a time resolution of 2-5 min and generates up to 2000 metabolite peaks over 2 h. We describe a fast, automated, observer-independent technique for processing { 1H-decoupled} 13C spectra. Quantified 13C spectroscopic signals, before and after the administration of [1- 13C]glucose and/or [1- 13C]acetate in human subjects are determined. Stepwise improvements of data processing are illustrated by examples of normal and pathological results. Variation in analysis of individual 13C resonances ranged between 2 and 14%. Using this method it is possible to reliably identify subtle metabolic effects of brain disease including Alzheimer's disease and epilepsy.

  17. 40 CFR 721.10373 - 1H-Imidazole, 1-(1-methylethyl)-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1H-Imidazole, 1-(1-methylethyl)-. 721... Substances § 721.10373 1H-Imidazole, 1-(1-methylethyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1H-imidazole, 1-(1-methylethyl)- (PMN...

  18. 40 CFR 721.10373 - 1H-Imidazole, 1-(1-methylethyl)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1H-Imidazole, 1-(1-methylethyl)-. 721... Substances § 721.10373 1H-Imidazole, 1-(1-methylethyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1H-imidazole, 1-(1-methylethyl)- (PMN...

  19. 40 CFR 721.10373 - 1H-Imidazole, 1-(1-methylethyl)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1H-Imidazole, 1-(1-methylethyl)-. 721... Substances § 721.10373 1H-Imidazole, 1-(1-methylethyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 1H-imidazole, 1-(1-methylethyl)- (PMN...

  20. 1H and 13C Solid-state NMR of Gossypium barbadense (Pima) Cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The interaction of water with cellulose and its influence on the nuclear spin dynamics in G. barbadense (Pima) cotton were investigated by 1H and 13C solid-state NMR techniques. 1H spin diffusion results from a Goldman-Shen experiment indicate that the water is multilayered. 1H MAS experiments pro...

  1. 1H and 13C Solid-state NMR of G. barbadense (Pima) Cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The interaction of water with cellulose and its influence on the nuclear spin dynamics in G. barbadense (Pima) cotton were investigated with 1H and 13C solid-state NMR techniques. 1H spin diffusion results from a Goldman-Shen experiment indicate that the water is multilayered. 1H MAS experiment...

  2. A Kinetic Model of Whole-Body Glucose Metabolism with Reference to the Domestic Dog (Canis lupus familiaris)

    PubMed Central

    McKnight, Leslie L.; Shoveller, Anna K.; Lopez, Secundino

    2015-01-01

    A new two-pool model to describe glucose kinetics in the steady state is presented. The pools are plasma glucose, Q1, and tissue glucose, Q2 (both µmol). The flows (all µmol/min) into the plasma pool (Pool 1) are absorbed glucose entry from dietary sources, labelled glucose infusion, and hepatic glucose production. There is one flow out of Pool 1, glucose uptake by the tissues. Inflows to the tissues pool (Pool 2) are from plasma and glycogenolysis. Outflows from Pool 2 are to plasma, glucose oxidation, and glycogenesis and other metabolism. Application of the model was illustrated using experimental data derived from healthy adult Labrador Retrievers in the fasted and fed (repeated meal feeding) states. In general, model derived estimates of glucose kinetics were representative of normal glucose metabolism, where rates of glucose production and uptake are similar and act to maintain blood glucose concentrations. Furthermore, estimates of within tissue glucose cycling indicated glycogenolysis in fasting and glycogenesis when fed. In the fasted state, model outputs were consistent with those reported in the canine literature derived using a single pool model.

  3. Impact of Adenovirus infection in host cell metabolism evaluated by (1)H-NMR spectroscopy.

    PubMed

    Silva, Ana Carina; P Teixeira, Ana; M Alves, Paula

    2016-08-10

    Adenovirus-based vectors are powerful vehicles for gene transfer applications in vaccination and gene therapy. Although highly exploited in the clinical setting, key aspects of the adenovirus biology are still not well understood, in particular the subversion of host cell metabolism during viral infection and replication. The aim of this work was to gain insights on the metabolism of two human cell lines (HEK293 and an amniocyte-derived cell line, 1G3) after infection with an adenovirus serotype 5 vector (AdV5). In order to profile metabolic alterations, we used (1)H-NMR spectroscopy, which allowed the quantification of 35 metabolites in cell culture supernatants with low sample preparation and in a relatively short time. Significant differences between both cell lines in non-infected cultures were identified, namely in glutamine and acetate metabolism, as well as by-product secretion. The main response to AdV5 infection was an increase in glucose consumption and lactate production rates. Moreover, cultures performed with or without glutamine supplementation confirmed the exhaustion of this amino acid as one of the main causes of lower AdV5 production at high cell densities (10- and 1.5-fold less specific yields in HEK293 and 1G3 cells, respectively), and highlighted different degrees of glutamine dependency of adenovirus replication in each cell line. The observed metabolic alterations associated with AdV5 infection and specificity of the host cell line can be useful for targeted bioprocess optimization. PMID:27215342

  4. Combining biochemical with (1)H NMR-based metabolomics approach unravels the antidiabetic activity of genipin and its possible mechanism.

    PubMed

    Shen, Xiao-Li; Liu, Huan; Xiang, Huan; Qin, Xue-Mei; Du, Guan-Hua; Tian, Jun-Sheng

    2016-09-10

    Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids and proteins. Genipin possesses a wide spectrum of biological activities including ameliorating effects on diabetes, but the definite mechanism of this effect remains unknown. To investigate the antidiabetic activities of genipin and explore the biochemical changes of serum endogenous metabolites on diabetic rats induced by alloxan, (1)H NMR spectroscopy coupled with multivariate data analysis was used to. All rats were randomly divided into six groups including negative control (NC) group, diabetic mellitus (DM) group, metformin hydrochloride group, high dose group of genipin, middle dose group of genipin and low dose group of genipin. Diabetes was induced by a single intraperitoneal injection of 120mg/kg body weight of alloxan. Serum samples were collected for the (1)H NMR-based metabolomics and clinical biochemical analysis. Daily oral administration of genipin (25, 50 and 100mg/kg body weight) and metformin hydrochloride (125mg/kg) for two weeks showed beneficial effects on blood glucose level (P<0.01). Significant differences in the metabolic profile as well as the result of biochemical parameters between the diabetic group and the control group were observed. The PLS-DA scores and corresponding loading plots demonstrated that genipin significantly restored the abnormal metabolic state. Detailed analysis of the altered metabolite levels indicated that genipin significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism and amino acid metabolism. Genipin showed the best anti-diabetic effects at a dose of 100mg/kg in rats. This finding indicates that chemical and metabolomic approaches could be powerful tools for the investigation of the biochemical changes in pathological conditions or drug treatment. PMID:27411170

  5. Ferrocene-functionalized 4-(2,5-Di(thiophen-2-yl)-1H-pyrrol-1-yl)aniline: a novel design in conducting polymer-based electrochemical biosensors.

    PubMed

    Ayranci, Rukiye; Demirkol, Dilek Odaci; Ak, Metin; Timur, Suna

    2015-01-01

    Herein, we report a novel ferrocenyldithiophosphonate functional conducting polymer and its use as an immobilization matrix in amperometric biosensor applications. Initially, 4-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)amidoferrocenyldithiophosphonate was synthesized and copolymerized with 4-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)benzenamine at graphite electrodes. The amino groups on the polymer were utilized for covalent attachment of the enzyme glucose oxidase. Besides, ferrocene on the backbone was used as a redox mediator during the electrochemical measurements. Prior to the analytical characterization, optimization studies were carried out. The changes in current signals at +0.45 V were proportional to glucose concentration from 0.5 to 5.0 mM. Finally, the resulting biosensor was applied for glucose analysis in real samples and the data were compared with the spectrophotometric Trinder method. PMID:25591169

  6. Ferrocene-Functionalized 4-(2,5-Di(thiophen-2-yl)-1H-pyrrol-1-yl)aniline: A Novel Design in Conducting Polymer-Based Electrochemical Biosensors

    PubMed Central

    Ayranci, Rukiye; Demirkol, Dilek Odaci; Ak, Metin; Timur, Suna

    2015-01-01

    Herein, we report a novel ferrocenyldithiophosphonate functional conducting polymer and its use as an immobilization matrix in amperometric biosensor applications. Initially, 4-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)amidoferrocenyldithiophosphonate was synthesized and copolymerized with 4-(2,5-di(thiophen-2-yl)-1H-pyrrol-1-yl)benzenamine at graphite electrodes. The amino groups on the polymer were utilized for covalent attachment of the enzyme glucose oxidase. Besides, ferrocene on the backbone was used as a redox mediator during the electrochemical measurements. Prior to the analytical characterization, optimization studies were carried out. The changes in current signals at +0.45 V were proportional to glucose concentration from 0.5 to 5.0 mM. Finally, the resulting biosensor was applied for glucose analysis in real samples and the data were compared with the spectrophotometric Trinder method. PMID:25591169

  7. Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach.

    PubMed

    Nagasaka, S; Tokuyama, K; Kusaka, I; Hayashi, H; Rokkaku, K; Nakamura, T; Kawakami, A; Higashiyama, M; Ishikawa, S; Saito, T

    1999-05-01

    Insulin sensitivity, glucose effectiveness, and endogenous glucose production (EGP) during stable-labeled, frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) were evaluated by a single-and two-compartment minimal model combined with nonparametric deconvolution in eleven nonobese Japanese type 2 diabetic patients. Four patients were treated with sulfonylureas, and the remaining seven with diet therapy alone. None had diabetic retinopathy and microalbuminuria. Their fasting glucose level was 117+/-7 mg/dl (mean +/- SE), and HbA1c was 6.6+/-0.3%. Age-, sex-, and BMI-matched subjects with normal glucose tolerance served as control subjects. Plasma insulin response to the stimuli and insulin sensitivity indexes (S(I), S(I)*, and S(I)2* were derived from a minimal model and single- and two-compartment-labeled minimal models) were impaired in the type 2 diabetic patients. The combined ability of glucose, per se, to increase its own uptake and suppress EGP (glucose effectiveness [SG]), which was derived from kinetic analysis of plasma glucose by a minimal model, was significantly lower in the type 2 diabetic patients (0.0132+/-0.0015 vs. 0.0203+/-0.0022; P<0.05). However, the ability of glucose, per se, to stimulate glucose uptake, assessed as S(G)* and S(G)2* from the kinetic analysis of labeled glucose by single- and two-compartment minimal model, was not impaired in those patients. EGP of the type 2 diabetic patients as a whole was suppressed to the level similar to that of the control subjects despite a higher plasma glucose level throughout FSIGT. When EGP in the diabetic subjects was analyzed, considering their recent glycemic control, the initial suppression was blunted in the patients with higher HbA1c levels. In conclusion, glucose mass action to stimulate glucose uptake remains near-normal in the lean Japanese type 2 diabetic patients of this study, whereas ability of glucose to suppress EGP is impaired in the patients with recent

  8. The effect of ispaghula (Fybogel and Metamucil) and guar gum on glucose tolerance in man.

    PubMed

    Jarjis, H A; Blackburn, N A; Redfern, J S; Read, N W

    1984-05-01

    The effects of incorporating Fybogel (3.5 and 7 g doses), Metamucil (7 g) or guar gum (2.5 and 14.5 g doses) in a drink containing 50 g glucose on plasma glucose, plasma insulin and gastric emptying were studied in thirty-eight normal volunteers. In addition, the effects of Fybogel (7 g) on glucose tolerance, plasma insulin and gastric emptying were measured in fourteen non-insulin-dependent diabetics. Both doses of guar gum significantly lowered plasma glucose and plasma insulin responses to the oral glucose load in normal subjects, although 14.5 g guar gum did not delay the half-time for gastric emptying. Neither Fybogel nor Metamucil had significant effects on plasma glucose responses in normal subjects. In addition, Fybogel (at either dose) had no significant effects on plasma insulin levels, or on gastric emptying in normal subjects or on plasma glucose and insulin responses in diabetic patients. The viscosity of ispaghula solutions ( Fybogel ) was lower than that of guar gum solutions. PMID:6326798

  9. Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism.

    PubMed

    Raboudi, N; Arem, R; Jones, R H; Chap, Z; Pena, J; Chou, J; Field, J B

    1989-01-01

    The effect of thyroid hormone excess on hepatic glucose balances and fractional hepatic extraction of insulin and glucagon was examined in six conscious dogs with catheters in the portal vein, hepatic vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. An oral glucose tolerance test was performed before and after the animals were made hyperthyroid by intramuscular thyroxine administration (100 micrograms.kg-1.day-1) for 10 days. In the basal state and after oral glucose, insulin and glucagon levels in the three vessels and the basal fractional hepatic extraction of insulin and glucagon were not significantly modified by thyroid hormone. These results suggest that in short-term thyrotoxicosis insulin secretion is not impaired, and the rise in fasting plasma glucose and increased hepatic glucose production could reflect hepatic insulin resistance, increased availability of precursors for gluconeogenesis, or increased glycogenolysis. Hyperthyroidism significantly increased basal flows in the portal vein (14.7 +/- 0.6 vs. 12.9 +/- 0.5 ml.kg-1.min-1), the hepatic artery (4.8 +/- 0.3 vs. 3.9 +/- 0.2 ml.kg-1.min-1) and vein (19.6 +/- 0.7 vs. 16.9 +/- 0.4 ml.kg-1.min-1), the fasting plasma glucose concentration (104 +/- 3 vs. 92 +/- 2 mg/dl), and basal hepatic glucose output (2.1 +/- 0.2 vs. 1.5 +/- 0.2 mg.kg-1.min-1). It did not alter the nonhepatic splanchnic uptake of glucose, the percent of orally administered glucose that appeared in the portal vein (47 +/- 2 vs. 45 +/- 11%), the percent of hepatic uptake of glucose (59 +/- 11 vs. 74 +/- 22%), or the shape of the glucose tolerance test. PMID:2643338

  10. A glucose-centric perspective of hyperglycemia.

    PubMed

    Ramasarma, T; Rafi, M

    2016-02-01

    Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (> 200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and

  11. Thermogenic Effect of Glucose in Hypothyroid Subjects

    PubMed Central

    Kozacz, Agnieszka; Grunt, Paulina; Steczkowska, Marta; Mikulski, Tomasz; Dąbrowski, Jan; Górecka, Monika; Sanocka, Urszula; Ziemba, Andrzej Wojciech

    2014-01-01

    The importance of thyroid hormone, catecholamines, and insulin in modification of the thermogenic effect of glucose (TEG) was examined in 34 healthy and 32 hypothyroid subjects. We calculated the energy expenditure at rest and during oral glucose tolerance test. Blood samples for determinations of glucose, plasma insulin, adrenaline (A), and noradrenaline (NA) were collected. It was found that TEG was lower in hypothyroid than in control group (19.68 ± 3.90 versus 55.40 ± 7.32 kJ, resp., P < 0.0004). Mean values of glucose and insulin areas under the curve were higher in women with hypothyroidism than in control group (286.79 ± 23.65 versus 188.41 ± 15.84 mmol/L·min, P < 0.003 and 7563.27 ± 863.65 versus 4987.72 ± 583.88 mU/L·min, P < 0.03 resp.). Maximal levels of catecholamines after glucose ingestion were higher in hypothyroid patients than in control subjects (Amax—0.69 ± 0.08 versus 0.30 ± 0.07 nmol/L, P < 0.0001, and NAmax—6.42 ± 0.86 versus 2.54 ± 0.30 nmol/L, P < 0.0002). It can be concluded that in hypothyroidism TEG and glucose tolerance are decreased while the adrenergic response to glucose administration is enhanced. Presumably, these changes are related to decreased insulin sensitivity and responsiveness to catecholamine action. PMID:24711817

  12. Effect of hydroxyethyl starch on blood glucose levels

    PubMed Central

    Shim, Soo Bin; Choi, Woo Young

    2016-01-01

    Background Hydroxyethyl starch (HES), a commonly used resuscitation fluid, has the property to induce hyperglycemia as it contains large ethyl starch, which can be metabolized to produce glucose. We evaluated the effect of 6% HES-130 on the blood glucose levels in non-diabetic patients undergoing surgery under spinal anesthesia. Methods Patients scheduled to undergo elective lower limb surgery were enrolled. Fifty-eight patients were divided into two groups according to the type of the main intravascular fluid used before spinal anesthesia (Group LR: lactated Ringer's solution, n = 30 vs. Group HES: 6% hydroxyethyl starch 130/0.4, n = 28). Blood glucose levels were measured at the following time points: 0 (baseline), 20 min (T1), 1 h (T2), 2 h (T3), 4 h (T4), and 6 h (T6). Results Mean blood glucose levels at T5 in the LR group and T4, T5 in the HES group, increased significantly compared to baseline. There were no significant changes in the serial differences of mean blood glucose levels from baseline between the two groups. Conclusions Administration of 6% HES-130 increased blood glucose levels within the physiologic limits, but the degree of glucose increase was not greater than that caused by administration of lactated Ringer's solution. In conclusion, we did not find evidence that 6% HES-130 induces hyperglycemia in non-diabetic patients. PMID:27482311

  13. Transformation of 1-O-(indole-3-acetyl)-beta-D-glucose into di-O-(indole-3-acetyl)-D-glucose catalysed by enzyme preparations from corn seedlings.

    PubMed

    Szmidt-Jaworska, A; Kesy, J; Kopcewicz, J

    1997-01-01

    A new enzymatic activity, which catalyses formation in vitro of di-O-(indole-3-acetyl)-D-glucose from 1-O-(indole-3-acetyl)-beta-D-glucose has been found in extracts of Zea mays seedlings. The structure of di-O-(indole-3-acetyl)-D-glucose, not as yet described, has been assigned by GC-MS, 1H NMR and ammonolysis. PMID:9360710

  14. Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized (1)H MRS study.

    PubMed

    Iltis, Isabelle; Koski, Dee M; Eberly, Lynn E; Nelson, Christopher D; Deelchand, Dinesh K; Valette, Julien; Ugurbil, Kamil; Lim, Kelvin O; Henry, Pierre-Gilles

    2009-08-01

    Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single-voxel (1)H-MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short-echo time sequence (STEAM) was used to acquire spectra in a 32-microL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre- vs. post-injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti-psychotic drugs in vivo. PMID:19338025

  15. Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX.

    PubMed

    Lu, Wei; Zhou, Qingzhang; Yang, Hao; Wang, Hao; Gu, Yexing; Shen, Qi; Xue, Jinglun; Dong, Xiaoyan; Chen, Jinzhong

    2016-06-01

    Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5 × 10(11) and 1 × 10(11) virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B. PMID:27052253

  16. Vascular Glucose Sensor Symposium

    PubMed Central

    Joseph, Jeffrey I; Torjman, Marc C.; Strasma, Paul J.

    2015-01-01

    Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, length of stay, and cost in a variety of critical care and non–critical care patient populations in the hospital. The results from prospective randomized clinical trials designed to determine the risks and benefits of intensive insulin therapy and tight glycemic control have been confusing; and at times conflicting. The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the great clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes. Automation and standardization of the glucose measurement process have the potential to significantly improve BG control, clinical outcome, safety and cost. PMID:26078254

  17. Recombinant glucose uptake system

    DOEpatents

    Ingrahm, Lonnie O.; Snoep, Jacob L.; Arfman, Nico

    1997-01-01

    Recombinant organisms are disclosed that contain a pathway for glucose uptake other than the pathway normally utilized by the host cell. In particular, the host cell is one in which glucose transport into the cell normally is coupled to PEP production. This host cell is transformed so that it uses an alternative pathway for glucose transport that is not coupled to PEP production. In a preferred embodiment, the host cell is a bacterium other than Z. mobilis that has been transformed to contain the glf and glk genes of Z. mobilis. By uncoupling glucose transport into the cell from PEP utilization, more PEP is produced for synthesis of products of commercial importance from a given quantity of biomass supplied to the host cells.

  18. All about Blood Glucose

    MedlinePlus

    ... Blood Glucose Before meals: 80 to 130 mg/dl My Usual Results My Goals ______ to ______ ______ to ______ 2 ... the start of a meal: below 180 mg/dl below ______ below ______ What’s the best way to keep ...

  19. Blood Glucose Monitoring Devices

    MedlinePlus

    ... Glucose NIH Medline Plus - Diabetes Spotlight FDA permits marketing of first system of mobile medical apps for ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  20. Sodium-Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport: From Bench to Bedside.

    PubMed

    Mudaliar, Sunder; Polidori, David; Zambrowicz, Brian; Henry, Robert R

    2015-12-01

    Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors. PMID:26604280

  1. Effects of ethanol ingestion on maternal and fetal glucose homeostasis

    SciTech Connect

    Singh, S.P.; Snyder, A.K.; Singh, S.K.

    1984-08-01

    Carbohydrate metabolism has been studied in the offspring of rats fed liqiud diet containing ethanol during gestation (EF group). Weight-matched control dams were given liquid diet either by the pair-fed technique (PF group) or ad libitum (AF group). EF and PF dams showed reduced food consumption and attenuated gain in body weight during the gestation period compared with the AF group. Blood glucose, liver glycogen, and plasma insulin levels were significantly reduced in EF and PF dams. Ethanol ingestion resulted in a significant decrease in litter survival and fetal body weight. At term, EF pups on average showed a 30% decrease in blood glucose levels and 40% decrease in plasma insulin levels compared with AF pups. One hour after birth, EF pups exhibited a marked increase in blood sugar level compared with either control group. Fetal hyperinsulinemia disappeared shortly after delivery in control pups, as expected; however, in EF pups, the fall in plasma insulin level was gradual. Fetal and neonatal plasma glucagon levels were not altered by ethanol exposure in utero. Blood glucose levels remained significantly low at 2 days of age in EF pups, but reached near control values at 4 days of age. Plasma insulin and glucagon were nearly equal in EF and control pups at 2 and 4 days of age. These results show aberrations in blood glucose, plasma insulin, and liver glycogen levels in offspring exposed to ethanol in utero.

  2. Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1

    PubMed Central

    Han, Yu-Chen; Zheng, Zhong-Liang; Zuo, Ze-Hua; Yu, Yan P; Chen, Rui; Tseng, George C; Nelson, Joel B; Luo, Jian-Hua

    2014-01-01

    Metallothioneins (MTs) are a group of metal binding proteins thought to play a role in the detoxification of heavy metals. Here we showed by microarray and validation analyses that MT1h, a member of MT, is down-regulated in many human malignancies. Low expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer. We found that the promoter region of MT1h was hypermethylated in cancer and that demethylation of the MT1h promoter reversed the suppression of MT1h expression. Forced expression of MT1h induced cell growth arrest, suppressed colony formation, retarded migration, and reduced invasion. SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. MT1h was found to interact with euchromatin histone methyltransferase 1 (EHMT1) and enhanced its methyltransferase activity on histone 3. Knocking down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 abrogated MT1h tumour suppressor activity. This demonstrates tumour suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation. PMID:23355073

  3. Regulation of glucose and glycogen metabolism during and after exercise.

    PubMed

    Jensen, Thomas E; Richter, Erik A

    2012-03-01

    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport is increased in the contracting muscle followed by a discussion of glycogen mobilization and synthesis by the action of glycogen phosphorylase and glycogen synthase, respectively. Finally, this review deals with the signalling relaying the well-described increased sensitivity of glucose transport to insulin in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation). PMID:22199166

  4. Regulation of glucose and glycogen metabolism during and after exercise

    PubMed Central

    Jensen, Thomas E; Richter, Erik A

    2012-01-01

    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport is increased in the contracting muscle followed by a discussion of glycogen mobilization and synthesis by the action of glycogen phosphorylase and glycogen synthase, respectively. Finally, this review deals with the signalling relaying the well-described increased sensitivity of glucose transport to insulin in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation). PMID:22199166

  5. Comparative effect of intraduodenal and intrajejunal glucose infusion on the gut-incretin axis response in healthy males.

    PubMed

    Wu, T; Thazhath, S S; Marathe, C S; Bound, M J; Jones, K L; Horowitz, M; Rayner, C K

    2015-01-01

    The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min(-1) over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was sampled frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI1 and the responses of GLP-1 and GIP (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1 (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut-incretin axis. PMID:25985092

  6. Measuring blood glucose in neonatal units: how does hemocue compare?

    PubMed Central

    Deshpande, S A; Matthews, J N; Platt, M P

    1996-01-01

    Rapid and reliable determination of blood glucose concentration is essential during the neonatal period to prevent adverse neurodevelopmental outcome from hypoglycaemia. Despite their unreliability, reagent strip methods continue to be used extensively in neonatal nurseries due to their rapidity and convenience. Recently, a new portable laboratory standard technique has been introduced (HemoCue B-Glucose system) for whole blood glucose determination. It is particularly suitable for near-patient testing in neonatal units. This new method, as well as other established methods of whole blood (Yellow Springs Instrument (YSI) and a hexokinase method on Cobas Bio), and plasma (Kodak Ektachem) glucose measurement, were therefore evaluated for their accuracy and concordance of measurements taken in the neonatal period. There were substantial discrepancies among the four methods of glucose measurement with wide limits of agreement between these methods. The glucose concentrations measured by HemoCue and YSI (n = 206), HemoCue and hexokinase (n = 113), HemoCue and plasma glucose on Ektachem (n = 69) and hexokinase and Ektachem (n = 66) were likely to differ by -29 to +61%, -23 to +56%, -36 to +65%, and -19 to +30%, respectively. Even the laboratory methods of blood glucose determination, therefore, can not be used interchangeably. Using a model based approach, the probabilities of "discordant" classification as hypo- or normo-glycaemia were estimated to be 6.8%, 6.5%, and 7.1% between HemoCue and YSI, HemoCue and hexokinase on Cobas Bio, and HemoCue and Ektachem analysers, respectively. In view of these low probabilities of discordant classification with other glucose analysers, the HemoCue system may offer a reasonable compromise between bedside and laboratory blood glucose estimations in neonates. PMID:8976688

  7. Alterations in glucose kinetics induced by pentobarbital anesthesia

    SciTech Connect

    Lang, C.H.; Bagby, G.J.; Hargrove, D.M.; Hyde, P.M.; Spitzer, J.J. )

    1987-12-01

    Because pentobarbital is often used in investigations related to carbohydrate metabolism, the in vivo effect of this drug on glucose homeostasis was studied. Glucose kinetics assessed by the constant intravenous infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose, were determined in three groups of catheterized fasted rats: conscious, anesthetized and body temperature maintained, and anesthetized but body temperature not maintained. After induction of anesthesia, marked hypothermia developed in rats not provided with external heat. Anesthetized rats that developed hypothermia showed a decrease in mean arterial blood pressure (25%) and heart rate (40%). Likewise, the plasma lactate concentration and the rates of glucose appearance, recycling, and metabolic clearance were reduced by 30-50% in the hypothermic anesthetized rats. Changes in whole-body carbohydrate metabolism were prevented when body temperature was maintained. Because plasma pentobarbital levels were similar between the euthermic and hypothermic rats during the first 2 h of the experiment, the rapid reduction in glucose metabolism in this latter group appears related to the decrease in body temperature. The continuous infusion of epinephrine produced alterations in glucose kinetics that were not different between conscious animals and anesthetized rats with body temperature maintained. Thus pentobarbital-anesthetized rats became hypothermic when kept at room temperature and exhibited marked decreases in glucose metabolism. Such changes were absent when body temperature was maintained during anesthesia.

  8. Palmitate stimulates glucose transport in rat adipocytes by a mechanism involving translocation of the insulin sensitive glucose transporter (GLUT4)

    NASA Technical Reports Server (NTRS)

    Hardy, R. W.; Ladenson, J. H.; Henriksen, E. J.; Holloszy, J. O.; McDonald, J. M.

    1991-01-01

    In rat adipocytes, palmitate: a) increases basal 2-deoxyglucose transport 129 +/- 27% (p less than 0.02), b) decreases the insulin sensitive glucose transporter (GLUT4) in low density microsomes and increases GLUT4 in plasma membranes and c) increases the activity of the insulin receptor tyrosine kinase. Palmitate-stimulated glucose transport is not additive with the effect of insulin and is not inhibited by the protein kinase C inhibitors staurosporine and sphingosine. In rat muscle, palmitate: a) does not affect basal glucose transport in either the soleus or epitrochlearis and b) inhibits insulin-stimulated glucose transport by 28% (p less than 0.005) in soleus but not in epitrochlearis muscle. These studies demonstrate a potentially important differential role for fatty acids in the regulation of glucose transport in different insulin target tissues.

  9. Electron-transfer mediator for a NAD-glucose dehydrogenase-based glucose sensor.

    PubMed

    Kim, Dong-Min; Kim, Min-yeong; Reddy, Sanapalli S; Cho, Jaegeol; Cho, Chul-ho; Jung, Suntae; Shim, Yoon-Bo

    2013-12-01

    A new electron-transfer mediator, 5-[2,5-di (thiophen-2-yl)-1H-pyrrol-1-yl]-1,10-phenanthroline iron(III) chloride (FePhenTPy) oriented to the nicotinamide adenine dinucleotide-dependent-glucose dehydrogenase (NAD-GDH) system was synthesized through a Paal-Knorr condensation reaction. The structure of the mediator was confirmed by Fourier-transform infrared spectroscopy, proton and carbon nucler magnetic resonance spectroscopy, and mass spectroscopy, and its electron-transfer characteristic for a glucose sensor was investigated using voltammetry and impedance spectroscopy. A disposable amperometric glucose sensor with NAD-GDH was constructed with FePhenTPy as an electron-transfer mediator on a screen printed carbon electrode (SPCE) and its performance was evaluated, where the addition of reduces graphene oxide (RGO) to the mediator showed the enhanced sensor performance. The experimental parameters to affect the analytical performance and the stability of the proposed glucose sensor were optimized, and the sensor exhibited a dynamic range between 30 mg/dL and 600 mg/dL with the detection limit of 12.02 ± 0.6 mg/dL. In the real sample experiments, the interference effects by acetaminophen, ascorbic acid, dopamine, uric acid, caffeine, and other monosaccharides (fructose, lactose, mannose, and xylose) were completely avoided through coating the sensor surface with the Nafion film containing lead(IV) acetate. The reliability of proposed glucose sensor was evaluated by the determination of glucose in artificial blood and human whole blood samples. PMID:24199942

  10. Disruption of GLUT1 glucose carrier trafficking in L6E9 and Sol8 myoblasts by the phosphatidylinositol 3-kinase inhibitor wortmannin.

    PubMed

    Kaliman, P; Viñals, F; Testar, X; Palacín, M; Zorzano, A

    1995-12-01

    In this study we have used wortmannin, a highly specific inhibitor of phosphatidylinositol (PI) 3-kinase, to assess the role of this enzyme on GLUT1 glucose carrier distribution and glucose transport activity in myoblasts from two skeletal-muscle cell lines, L6E9 and Sol8. As detected in L6E9 cells, myoblasts exhibited basal and insulin-stimulated PI 3-kinase activities. Incubation of intact myoblasts with wortmannin resulted in a marked inhibition of both basal and insulin-stimulated PI 3-kinase activities. L6E9 and Sol8 myoblasts showed basal and insulin-stimulated glucose transport activities, both of them inhibited by wortmannin in a dose-dependent manner (IC50 approximately 10-20 nM). Concomitantly, immunofluorescence analysis revealed that 1 h treatment with wortmannin led to a dramatic intracellular accumulation of GLUT1 carriers (the main glucose transporter expressed in L6E9 and Sol8 myoblasts) in both cell systems. The effect of wortmannin on GLUT1 cellular redistribution was independent of the presence of insulin. The cellular distribution of two structural plasma-membrane components such as beta 1-integrin or the alpha 1 subunit of the Na(+)-K(+)-ATPase were unaffected by wortmannin in both the absence and the presence of insulin. As a whole, our results indicate that PI 3-kinase is necessary to basal and insulin-stimulated glucose transport in L6E9 and Sol8 myoblasts. Moreover, immunofluorescence assays suggest that in both cellular models there is a constitutive GLUT 1 trafficking pathway (independent of insulin) that involves PI 3-kinase and which, when blocked, locks GLUT1 in a perinuclear compartment. PMID:8526858

  11. Disruption of GLUT1 glucose carrier trafficking in L6E9 and Sol8 myoblasts by the phosphatidylinositol 3-kinase inhibitor wortmannin.

    PubMed Central

    Kaliman, P; Viñals, F; Testar, X; Palacín, M; Zorzano, A

    1995-01-01

    In this study we have used wortmannin, a highly specific inhibitor of phosphatidylinositol (PI) 3-kinase, to assess the role of this enzyme on GLUT1 glucose carrier distribution and glucose transport activity in myoblasts from two skeletal-muscle cell lines, L6E9 and Sol8. As detected in L6E9 cells, myoblasts exhibited basal and insulin-stimulated PI 3-kinase activities. Incubation of intact myoblasts with wortmannin resulted in a marked inhibition of both basal and insulin-stimulated PI 3-kinase activities. L6E9 and Sol8 myoblasts showed basal and insulin-stimulated glucose transport activities, both of them inhibited by wortmannin in a dose-dependent manner (IC50 approximately 10-20 nM). Concomitantly, immunofluorescence analysis revealed that 1 h treatment with wortmannin led to a dramatic intracellular accumulation of GLUT1 carriers (the main glucose transporter expressed in L6E9 and Sol8 myoblasts) in both cell systems. The effect of wortmannin on GLUT1 cellular redistribution was independent of the presence of insulin. The cellular distribution of two structural plasma-membrane components such as beta 1-integrin or the alpha 1 subunit of the Na(+)-K(+)-ATPase were unaffected by wortmannin in both the absence and the presence of insulin. As a whole, our results indicate that PI 3-kinase is necessary to basal and insulin-stimulated glucose transport in L6E9 and Sol8 myoblasts. Moreover, immunofluorescence assays suggest that in both cellular models there is a constitutive GLUT 1 trafficking pathway (independent of insulin) that involves PI 3-kinase and which, when blocked, locks GLUT1 in a perinuclear compartment. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8526858

  12. Analysis of Eisenia fetida earthworm responses to sub-lethal C60 nanoparticle exposure using (1)H-NMR based metabolomics.

    PubMed

    Lankadurai, Brian P; Nagato, Edward G; Simpson, André J; Simpson, Myrna J

    2015-10-01

    The enhanced production and environmental release of Buckminsterfullerene (C60) nanoparticles will likely increase the exposure and risk to soil dwelling organisms. We used (1)H NMR-based metabolomics to investigate the response of Eisenia fetida earthworms to sub-lethal C60 nanoparticle exposure in both contact and soil tests. Principal component analysis of (1)H NMR data showed clear separation between controls and exposed earthworms after just 2 days of exposure, however as exposure time increased the separation decreased in soil but increased in contact tests suggesting potential adaptation during soil exposure. The amino acids leucine, valine, isoleucine and phenylalanine, the nucleoside inosine, and the sugars glucose and maltose emerged as potential bioindicators of exposure to C60 nanoparticles. The significant responses observed in earthworms using NMR-based metabolomics after exposure to very low concentrations of C60 nanoparticles suggests the need for further investigations to better understand and predict their sub-lethal toxicity. PMID:26024814

  13. Metabolomic quality control of commercial Asian ginseng, and cultivated and wild American ginseng using (1)H NMR and multi-step PCA.

    PubMed

    Zhao, Huiying; Xu, Jin; Ghebrezadik, Helen; Hylands, Peter J

    2015-10-10

    Ginseng, mainly Asian ginseng and American ginseng, is the most widely consumed herbal product in the world . However, the existing quality control method is not adequate: adulteration is often seen in the market. In this study, 31 batches of ginseng from Chinese stores were analyzed using (1)H NMR metabolite profiles together with multi-step principal component analysis. The most abundant metabolites, sugars, were excluded from the NMR spectra after the first principal component analysis, in order to reveal differences contributed by less abundant metabolites. For the first time, robust, distinctive and representative differences of Asian ginseng from American ginseng were found and the key metabolites responsible were identified as sucrose, glucose, arginine, choline, and 2-oxoglutarate and malate. Differences between wild and cultivated ginseng were identified as ginsenosides. A substitute cultivated American ginseng was noticed. These results demonstrated that the combination of (1)H NMR and PCA is effective in quality control of ginseng. PMID:26037159

  14. Selective Detection of 1H NMR Resonances of CH n Groups Using a Heteronuclear Maximum-Quantum Filter and Pulsed Field Gradients

    NASA Astrophysics Data System (ADS)

    Liu, M.; Farrant, R. D.; Nicholson, J. K.; Lindon, J. C.

    A number of approaches are described for the provision of separate one-dimensional 1H NMR spectra of CH, CH 2, and CH 3 groups utilizing the natural-abundance 13C spins and based upon the selection of the maximum multiple-quantum coherences of the various groups, This sequence is termed edited maximum-quantum proton spectroscop y (MAXY) spectroscopy, The replacement of phase cycling with the application of z magnetic field gradient pulses is also demonstrated, The editing approach is demonstrated using the 1H NMR spectrum of dexamethasone in DMSO- d6 solution, Extension to a complex mixture biofluid is exemplified by the CH 3-only 1H NMR spectrum of human seminal plasma. This aid to the assignment of endogenous metabolite resonances is demonstrated to result in dramatic spectral simplification.

  15. Disproportionately elevated proinsulinemia is observed at modestly elevated glucose levels within the normoglycemic range.

    PubMed

    Lorenzo, Carlos; Hanley, Anthony J; Rewers, Marian J; Haffner, Steven M

    2014-08-01

    We aimed to evaluate disproportional proinsulinemia in the pre-diabetic state by analyzing the cross-sectional differences between proinsulin (PI) ratios across the entire range of fasting and 2-h plasma glucose. The study sample was 1,016 participants in the insulin resistance atherosclerosis study, who had no previous diagnosis of diabetes. Insulin sensitivity index (SI) and acute insulin response (AIR) were measured by the frequently sampled intravenous glucose tolerance test. Fasting intact and split PI-to-insulin ratios (PI/I, SPI/I), intact and split PI-to-C-peptide ratios (PI/C-pep, SPI/C-pep), and SI-adjusted AIR were assessed as a function of fasting and 2-h glucose levels. SI-adjusted AIR was decreased (fasting glucose 96-98 mg/dl; 2-h glucose 120-131 mg/dl) and SPI/C-pep increased at modestly elevated fasting glucose and 2-h glucose within the normal glucose tolerance range (fasting glucose 96-98 mg/dl; 2-h glucose 132-142 mg/dl). PI/I was not increased until plasma glucose values were in the diabetic range of fasting glucose (>126 mg/dl) or the impaired glucose tolerance range of 2-h glucose (143-156 mg/dl). SPI/I and PI/C-pep as a function of fasting and 2-h glucose were situated between the curves for SPI/C-pep and PI/I. In conclusion, inappropriate amounts of PI and conversion intermediaries are demonstrated at modestly elevated glucose levels within the normoglycemic range. Ratios that use SPI in the numerator or C-pep in the denominator (and especially SPI/C-pep) are more sensitive to early glycemic excursions than PI/I. Disordered processing of PI may accompany derangements in early insulin secretory response. PMID:24532116

  16. Enzymatic growth of quantum dots: applications to probe glucose oxidase and horseradish peroxidase and sense glucose.

    PubMed

    Saa, Laura; Pavlov, Valeri

    2012-11-19

    Three innovative assays are developed for the detection of enzymatic activities of glucose oxidase (GOx) and horseradish peroxidase (HRP) by the generation of CdS quantum dots (QDs) in situ using non-conventional enzymatic reactions. In the first assay, GOx catalyzes the oxidation of 1-thio-β-D-glucose to give 1-thio-β-D-gluconic acid. The latter is spontaneously hydrolyzed to β-D-gluconic acid and H2 S, which in the presence of cadmium nitrate yields fluorescent CdS nanoparticles. In the second assay HRP catalyzes the oxidation of sodium thiosulfate with hydrogen peroxide generating H2 S and consequently CdS QDs. The combination of GOx with HRP, allowed quantification of glucose in plasma by following growth of fluorescent QDs. PMID:22887879

  17. Glucose homoeostasis following injury.

    PubMed Central

    Wright, P. D.

    1979-01-01

    Metabolic changes following injury have been observed for many years, and John Hunter discussed such changes in 1794. Changes in carbohydrate metabolism have been observed for a similar length of time, and glycosuria and hyperglycaemia have been reported by a number of observers. This paper records and quantitates the extent of hyperglycaemia in patients undergoing surgery of different degrees of severity and relates them to changes in blood insulin, growth hormone, cortisol, and catecholamine concentrations. Further animal studies were performed which suggested that a fall in intracellular glucose utilisation may be a contributory factor. The use of isotope labelling of glucose in man has enabled further studies to be done to clarify changes in exchangeable glucose mass, replacement rate, and space both in the normal situation and in the presence of infusions of glucagon, noradrenaline, glucose, and amino-acids. The hyperglycaemia is clearly the result of a complex interaction of changes in the availability and activity of hormones which control glucose metabolism both within and outside the cell. PMID:496234

  18. Investigating the effect of glucose on aortic pulse wave velocity using pancreatic clamping methodology.

    PubMed

    Puzantian, Houry; Teff, Karen; Townsend, Raymond R

    2015-05-01

    Aortic stiffness, determined by carotid-femoral pulse wave velocity (cfPWV), independently predicts cardiovascular outcomes. Recent studies suggest that glucose levels influence arterial stiffness indices. It is not clear, however, whether glucose affects cfPWV independently of glucoregulatory hormones. The aim of this study was to utilize a pancreatic clamping approach to determine whether plasma glucose independently predicts cfPWV. Healthy participants (N = 10) underwent pancreatic clamping to control glucose at varying concentrations using a 20% dextrose infusion while suppressing endogenous glucagon, insulin, and growth hormone by octreotide and replacing the hormones intravenously to achieve basal concentrations. Tonometric cfPWV, blood pressure, heart rate, plasma glucose, glucagon, insulin, growth hormone, and vasoactive biomarkers were measured. Plasma glucose levels of 150 mg/dl at 1 hr and 200 mg/dl at 2 hr postbaseline were achieved. There were no significant changes in cfPWV (5.8 m/s at 0 hr, 5.9 m/s at 1 hr, and 5.9 m/s at 2 hr) with increased glucose levels. There were small increases in insulin secretion. A definitive role for glucose in cfPWV modulation was not determined; there is a potential role for insulin as a cfPWV modulator. Continued efforts in clarifying the independent roles of glucose and insulin can elucidate novel vessel-related targets for cardiovascular disease prevention and management in patients with impaired glucose tolerance and diabetes. PMID:25802385

  19. Electroacupuncture improves glucose tolerance through cholinergic nerve and nitric oxide synthase effects in rats.

    PubMed

    Lin, Rong-Tsung; Chen, Ching-Yuan; Tzeng, Chung-Yuh; Lee, Yu-Chen; Cheng, Yu-Wen; Chen, Ying-I; Ho, Wai-Jane; Cheng, Juei-Tang; Lin, Jaung-Geng; Chang, Shih-Liang

    2011-04-25

    The purpose of this investigation was to evaluate the effect and mechanisms of electroacupuncture (EA) at the bilateral Zusanli acupoints (ST-36) on glucose tolerance in normal rats. Intravenous glucose tolerance test (IVGTT) was performed to examine the effects of electroacupuncture (EA) on glucose tolerance in rats. The EA group underwent EA at the ST-36, with settings of 15 Hz, 10 mA, and 60 min; the control group underwent the same treatments, but without EA. Atropine, hemicholinium-3 (HC-3) or NG-nitro-L-arginine methyl ester (L-NAME) were injected into the rats alone or simultaneously and EA was performed to investigate differences in plasma glucose levels compared to the control group. Plasma samples were obtained for assaying plasma glucose and free fatty acid (FFA) levels. Western blot was done to determine the insulin signal protein and nNOS to exam the correlation between EA and improvement in glucose tolerance. The EA group had significantly lower plasma glucose levels compared to the control group. Plasma glucose levels differed significantly between the EA and control groups after the administration of L-NAME, atropine, or HC-3 treatments alone, but there were no significant differences in plasma glucose with combined treatment of L-NAME and atropine or L-NAME and HC-3. EA decreased FFA levels and enhanced insulin signal protein (IRS1) and nNOS activities in skeletal muscle during IVGTT. In summary, EA stimulated cholinergic nerves and nitric oxide synthase for lowering plasma FFA levels to improve glucose tolerance. PMID:21376780

  20. Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats.

    PubMed

    Tunnicliffe, Jasmine M; Eller, Lindsay K; Reimer, Raylene A; Hittel, Dustin S; Shearer, Jane

    2011-10-01

    Regular coffee consumption significantly lowers the risk of type 2 diabetes (T2D). Coffee contains thousands of compounds; however, the specific component(s) responsible for this reduced risk is unknown. Chlorogenic acids (CGA) found in brewed coffee inhibit intestinal glucose uptake in vitro. The objective of this study was to elucidate the mechanisms by which CGA acts to mediate blood glucose response in vivo. Conscious, unrestrained, male Sprague-Dawley rats were chronically catheterized and gavage-fed a standardized meal (59% carbohydrate, 25% fat, 12% protein), administered with or without CGA (120 mg·kg(-1)), in a randomized crossover design separated by a 3-day washout period. Acetaminophen was co-administered to assess the effects of CGA on gastric emptying. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured. GLP-1 response in the presence of glucose and CGA was further examined, using the human colon cell line NCI-H716. Total area under the curve (AUC) for blood glucose was significantly attenuated in rats fed CGA (p < 0.05). Despite this, no differences in plasma insulin or nonesterified fatty acids were observed, and gastric emptying was not altered. Plasma GIP response was blunted in rats fed CGA, with a lower peak concentration and AUC up to 180 min postprandially (p < 0.05). There were no changes in GLP-1 secretion in either the in vivo or in vitro study. In conclusion, CGA treatment resulted in beneficial effects on blood glucose response, with alterations seen in GIP concentrations. Given the widespread consumption and availability of coffee, CGA may be a viable prevention tool for T2D. PMID:21977912

  1. Effect of insulin immunization on glucose tolerance in normal rats.

    PubMed

    Froguel, P; Reach, G

    1987-01-01

    Normal rats were immunized with insulin and Freund's adjuvant and submitted to an intravenous glucose tolerance test. Plasma glucose and free and total IRI levels were determined and compared to those observed in untreated rats, and in animals injected with the Freund's adjuvant used for the immunization procedure. In six of the 15 insulin injected animals, a significant amount of IRI (more than 100 mU/l) was found to circulate in bound form. In these animals, the fasting plasma glucose concentrations, and glucose disappearance rates were not different from those observed in all the other groups. However, the rise in their free IRI level was delayed, as was the return to basal level: 45 min after glucose injection, the free IRI concentration was still 98 +/- 29 mU/l in the six immunized rats vs 14 +/- 6 mU/l in those treated with Freund's adjuvant (p less than 0.01). Furthermore, the secondary nadir in the plasma glucose concentration observed at 60 min after glucose injection, was lower in the immunized rats (5.4 +/- 0.5 vs 6.8 +/- 0.3 mmol/l, p less than 0.05). It is concluded that in normal animals, IRI binding in proportions similar to those commonly observed in insulin-treated diabetic patients does not alter glucose tolerance but might lead to abnormal insulin kinetics and secondary hypoglycemia. These results might have implications for the use of closed-loop insulin delivery systems in type 1 (insulin-dependent) diabetic patients with insulin antibodies. PMID:3123287

  2. SGLT2 Mediates Glucose Reabsorption in the Early Proximal Tubule

    PubMed Central

    Platt, Kenneth A.; Cunard, Robyn; Schroth, Jana; Whaley, Jean; Thomson, Scott C.; Koepsell, Hermann; Rieg, Timo

    2011-01-01

    Mutations in the gene encoding for the Na+-glucose co-transporter SGLT2 (SLC5A2) associate with familial renal glucosuria, but the role of SGLT2 in the kidney is incompletely understood. Here, we determined the localization of SGLT2 in the mouse kidney and generated and characterized SGLT2-deficient mice. In wild-type (WT) mice, immunohistochemistry localized SGLT2 to the brush border membrane of the early proximal tubule. Sglt2−/− mice had glucosuria, polyuria, and increased food and fluid intake without differences in plasma glucose concentrations, GFR, or urinary excretion of other proximal tubular substrates (including amino acids) compared with WT mice. SGLT2 deficiency did not associate with volume depletion, suggested by similar body weight, BP, and hematocrit; however, plasma renin concentrations were modestly higher and plasma aldosterone levels were lower in Sglt2−/− mice. Whole-kidney clearance studies showed that fractional glucose reabsorption was significantly lower in Sglt2−/− mice compared with WT mice and varied in Sglt2−/− mice between 10 and 60%, inversely with the amount of filtered glucose. Free-flow micropuncture revealed that for early proximal collections, 78 ± 6% of the filtered glucose was reabsorbed in WT mice compared with no reabsorption in Sglt2−/− mice. For late proximal collections, fractional glucose reabsorption was 93 ± 1% in WT and 21 ± 6% in Sglt2−/− mice, respectively. These results demonstrate that SGLT2 mediates glucose reabsorption in the early proximal tubule and most of the glucose reabsorption by the kidney, overall. This mouse model mimics and explains the glucosuric phenotype of individuals carrying SLC5A2 mutations. PMID:20616166

  3. Glucose infusion does not suppress increased lipolysis after abdominal surgery.

    PubMed

    Schricker, T; Carli, F; Lattermann, R; Wachter, U; Georgieff, M

    2001-02-01

    The purpose of this study was to investigate the effect of glucose infusion on lipid metabolism after abdominal surgery. Patients (n = 6) with non-metastasized colorectal carcinoma were investigated on the second day after surgery and healthy volunteers were studied after an overnight fast. The rates of glycerol appearance (R(a) glycerol), i.e., lipolysis rates, were assessed by primed continuous infusion of [1,1,2,3,3,-5H2]glycerol before and after 3 h of glucose infusion (4 mg x kg(-1) x min(-1)). Plasma concentrations of glycerol, free fatty acids, glucose, lactate, insulin, and glucagon were determined. Fasting R(a) glycerol was higher in patients than in volunteers (7.7 +/- 1.8 versus 1.9 +/- 0.3 micromol x kg(-1) x min(-1), P < 0.05). Glucose infusion suppressed the R(a) glycerol in volunteers to 1.0 +/- 0.2 micromol x kg(-1) x min(-1) (P < 0.05), whereas lipolysis was not affected in patients. Plasma concentrations of glycerol and free fatty acids similarly decreased during glucose administration by 50% in both groups (P < 0.05). In contrast to the patients, a significant correlation (r = 0.78, P < 0.05) between the R(a) glycerol and plasma glycerol concentration was observed in normal subjects. The hyperglycemic response to glucose infusion was significantly more pronounced (P < 0.05) in patients (10.7 +/- 0.7 mmol/L) than in volunteers (7.1 +/- 0.4 mmol/L), whereas the plasma insulin increased to the same extent in the two groups (P < 0.001). In conclusion, lipolysis rates are increased after abdominal surgery and glucose administration, most likely due to insulin resistance, and fail to inhibit stimulated whole-body lipolysis. PMID:11240333

  4. Insulin, catecholamines, glucose and antioxidant enzymes in oxidative damage during different loads in healthy humans.

    PubMed

    Koska, J; Blazícek, P; Marko, M; Grna, J D; Kvetnanský, R; Vigas, M

    2000-01-01

    Exercise, insulin-induced hypoglycemia and oral glucose loads (50 g and 100 g) were used to compare the production of malondialdehyde and the activity of antioxidant enzymes in healthy subjects. Twenty male volunteers participated in the study. Exercise consisted of three consecutive work loads on a bicycle ergometer of graded intensity (1.5, 2.0, and 2.5 W/kg, 6 min each). Hypoglycemia was induced by insulin (Actrapid MC Novo, 0.1 IU/kg, i.v.). Oral administration of 50 g and 100 g of glucose was given to elevate plasma glucose. The activity of superoxide dismutase (SOD) was determined in red blood cells, whereas glutathione peroxidase (GSH-Px) activity was measured in whole blood. The concentration of malondialdehyde (MDA) was determined by HPLC, catecholamines were assessed radioenzymatically and glucose was measured by the glucose-oxidase method. Exercise increased MDA concentrations, GSH-Px and SOD activities as well as plasma noradrenaline and adrenaline levels. Insulin hypoglycemia increased plasma adrenaline levels, but the concentrations of MDA and the activities of GSH-Px and SOD were decreased. Hyperglycemia increased plasma MDA concentrations, but the activities of GSH-Px and SOD were significantly higher after a larger dose of glucose only. Plasma catecholamines were unchanged. These results indicate that the transient increase of plasma catecholamine and insulin concentrations did not induce oxidative damage, while glucose already in the low dose was an important triggering factor for oxidative stress. PMID:10984077

  5. How to monitor blood glucose.

    PubMed

    Dunning, Trisha

    2016-01-27

    Rationale and key points Capillary blood glucose monitoring is an essential component of diabetes care. Blood glucose tests provide important information about how the body is controlling blood glucose metabolism, and the effect of glucose-lowering medicines, illness and stress. ▶ The nurse should consider the rationale for testing blood glucose each time they perform a test, and reflect on the result, taking into consideration the patient's blood glucose target range and recommended care guidelines. ▶ Blood glucose testing times and testing frequency should be planned to suit the glucose-lowering medicine regimen and the clinical situation. Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. What you have gained from this article. 2. How this article will influence your practice when monitoring blood glucose. Subscribers can upload their reflective accounts at: rcni.com/portfolio . PMID:26967884

  6. 4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities

    PubMed Central

    Monastyrskyi, Andrii; Kyle, Dennis E.; Manetsch, Roman

    2015-01-01

    Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes will be discussed. PMID:25116582

  7. Automated structure verification based on a combination of 1D (1)H NMR and 2D (1)H - (13)C HSQC spectra.

    PubMed

    Golotvin, Sergey S; Vodopianov, Eugene; Pol, Rostislav; Lefebvre, Brent A; Williams, Antony J; Rutkowske, Randy D; Spitzer, Timothy D

    2007-10-01

    A method for structure validation based on the simultaneous analysis of a 1D (1)H NMR and 2D (1)H - (13)C single-bond correlation spectrum such as HSQC or HMQC is presented here. When compared with the validation of a structure by a 1D (1)H NMR spectrum alone, the advantage of including a 2D HSQC spectrum in structure validation is that it adds not only the information of (13)C shifts, but also which proton shifts they are directly coupled to, and an indication of which methylene protons are diastereotopic. The lack of corresponding peaks in the 2D spectrum that appear in the 1D (1)H spectrum, also gives a clear picture of which protons are attached to heteroatoms. For all these benefits, combined NMR verification was expected and found by all metrics to be superior to validation by 1D (1)H NMR alone. Using multiple real-life data sets of chemical structures and the corresponding 1D and 2D data, it was possible to unambiguously identify at least 90% of the correct structures. As part of this test, challenging incorrect structures, mostly regioisomers, were also matched with each spectrum set. For these incorrect structures, the false positive rate was observed as low as 6%. PMID:17694570

  8. Assessing Glucose Uptake through the Yeast Hexose Transporter 1 (Hxt1)

    PubMed Central

    Roy, Adhiraj; Dement, Angela D.; Cho, Kyu Hong; Kim, Jeong-Ho

    2015-01-01

    The transport of glucose across the plasma membrane is mediated by members of the glucose transporter family. In this study, we investigated glucose uptake through the yeast hexose transporter 1 (Hxt1) by measuring incorporation of 2-NBDG, a non-metabolizable, fluorescent glucose analog, into the yeast Saccharomyces cerevisiae. We find that 2-NBDG is not incorporated into the hxt null strain lacking all glucose transporter genes and that this defect is rescued by expression of wild type Hxt1, but not of Hxt1 with mutations at the putative glucose-binding residues, inferred from the alignment of yeast and human glucose transporter sequences. Similarly, the growth defect of the hxt null strain on glucose is fully complemented by expression of wild type Hxt1, but not of the mutant Hxt1 proteins. Thus, 2-NBDG, like glucose, is likely to be transported into the yeast cells through the glucose transport system. Hxt1 is internalized and targeted to the vacuole for degradation in response to glucose starvation. Among the mutant Hxt1 proteins, Hxt1N370A and HXT1W473A are resistant to such degradation. Hxt1N370A, in particular, is able to neither uptake 2-NBDG nor restore the growth defect of the hxt null strain on glucose. These results demonstrate 2-NBDG as a fluorescent probe for glucose uptake in the yeast cells and identify N370 as a critical residue for the stability and function of Hxt1. PMID:25816250

  9. Ethanolic extract of Allium cepa stimulates glucose transporter typ 4-mediated glucose uptake by the activation of insulin signaling.

    PubMed

    Gautam, Sudeep; Pal, Savita; Maurya, Rakesh; Srivastava, Arvind K

    2015-02-01

    The present work was undertaken to investigate the effects and the molecular mechanism of the standardized ethanolic extract of Allium cepa (onion) on the glucose transport for controlling diabetes mellitus. A. cepa stimulates glucose uptake by the rat skeletal muscle cells (L6 myotubes) in both time- and dose-dependent manners. This effect was shown to be mediated by the increased translocation of glucose transporter typ 4 protein from the cytoplasm to the plasma membrane as well as the synthesis of glucose transporter typ 4 protein. The effect of A. cepa extract on glucose transport was stymied by wortmannin, genistein, and AI½. In vitro phosphorylation analysis revealed that, like insulin, A. cepa extract also enhances the tyrosine phosphorylation of the insulin receptor-β, insulin receptor substrate-1, and the serine phosphorylation of Akt under both basal and insulin-stimulated conditions without affecting the total amount of these proteins. Furthermore, it is also shown that the activation of Akt is indispensable for the A. cepa-induced glucose uptake in L6 myotubes. Taken together, these findings provide ample evidence that the ethanolic extract of A. cepa stimulates glucose transporter typ 4 translocation-mediated glucose uptake by the activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt dependent pathway. PMID:25654406

  10. Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

    PubMed

    Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

    1995-05-01

    A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects. PMID:7587920

  11. Effect of the Artificial Sweetener, Acesulfame Potassium, a Sweet Taste Receptor Agonist, on Glucose Uptake in Small Intestinal Cell Lines

    PubMed Central

    Zheng, Ye; Sarr, Michael G.

    2012-01-01

    Sweet taste receptors may enhance glucose absorption. AIM To explore the cell biology of sweet taste receptors on glucose uptake. HYPOTHESIS Artificial sweeteners increase glucose uptake via activating sweet taste receptors in the enterocyte to translocate GLUT2 to the apical membrane through the PLC βII pathway. METHODS Caco-2, RIE-1, and IEC-6 cells, starved from glucose for 1 h were pre-incubated with 10 mM acesulfame potassium (AceK). Glucose uptake was measured by incubating cells for 1 to 10 min with 0.5–50 mM glucose with or without U-73122, chelerythrine, and cytochalasin B. RESULTS In Caco-2 and RIE-1 cells, 10 mM AceK increased glucose uptake by 20~30% at glucose ≥ 25 mM, but not in lesser glucose concentrations (≤10 mM), nor at 1 min or 10 min incubations. U-73122 inhibited uptake at glucose ≥ 25 mM and for 5 min incubation; chelerythrine and cytochalasin B had similar effects. No effect occurred in IEC-6 cells. SUMMARY Activation of sweet taste receptors had no effect on glucose uptake in low (<25 mM) glucose concentrations but increased uptake at greater concentrations (≥ 25 mM). CONCLUSIONS Role of artificial sweeteners on glucose uptake appears to act in part by effects on the enterocyte itself. PMID:22948835

  12. An ultrasensitive, non-enzymatic glucose assay via gold nanorod-assisted generation of silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Xianyu, Yunlei; Sun, Jiashu; Li, Yixuan; Tian, Yue; Wang, Zhuo; Jiang, Xingyu

    2013-06-01

    This report demonstrates a colorimetric, non-enzymatic glucose assay with a low detection limit of 0.07 μM based on negatively charged gold nanorod-enhanced redox reaction. This glucose assay could generate silver nanoparticles as the readout that can be visualized by the naked eye, and only 4 femtomoles of nanorods are needed for glucose determination in one human plasma sample.This report demonstrates a colorimetric, non-enzymatic glucose assay with a low detection limit of 0.07 μM based on negatively charged gold nanorod-enhanced redox reaction. This glucose assay could generate silver nanoparticles as the readout that can be visualized by the naked eye, and only 4 femtomoles of nanorods are needed for glucose determination in one human plasma sample. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr01697h

  13. Sodium-Glucose Cotransporter 2 Inhibitors: Possible Anti-Atherosclerotic Effects Beyond Glucose Lowering.

    PubMed

    Yanai, Hidekatsu; Katsuyama, Hisayuki; Hamasaki, Hidetaka; Adachi, Hiroki; Moriyama, Sumie; Yoshikawa, Reo; Sako, Akahito

    2016-01-01

    The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We searched by using Pubmed, and found 770 published articles about SGLT-2 inhibitors. Among 10 kinds of SGLT-2 inhibitors, the number of published articles about dapagliflozin was the greatest among SGLT-2 inhibitors. Since SGLT-2 inhibitors have similar chemical structures, we concentrated on the published articles about dapagliflozin. SGLT-2 inhibitors are proved to be significantly associated with weight loss and reduction of blood pressure by a relatively large number of studies. The studies investigating effects of dapagliflozin on visceral fat, insulin sensitivity, serum lipids, inflammation and adipocytokines are very limited. An influence of increase in glucagon secretion by SGLT-2 inhibitors on metabolic risk factors remains unknown. PMID:26668677

  14. Stereospecificity of (1) H, (13) C and (15) N shielding constants in the isomers of methylglyoxal bisdimethylhydrazone: problem with configurational assignment based on (1) H chemical shifts.

    PubMed

    Afonin, Andrei V; Pavlov, Dmitry V; Ushakov, Igor A; Keiko, Natalia A

    2012-07-01

    In the (13) C NMR spectra of methylglyoxal bisdimethylhydrazone, the (13) C-5 signal is shifted to higher frequencies, while the (13) C-6 signal is shifted to lower frequencies on going from the EE to ZE isomer following the trend found previously. Surprisingly, the (1) H-6 chemical shift and (1) J(C-6,H-6) coupling constant are noticeably larger in the ZE isomer than in the EE isomer, although the configuration around the -CH═N- bond does not change. This paradox can be rationalized by the C-H⋯N intramolecular hydrogen bond in the ZE isomer, which is found from the quantum-chemical calculations including Bader's quantum theory of atoms in molecules analysis. This hydrogen bond results in the increase of δ((1) H-6) and (1) J(C-6,H-6) parameters. The effect of the C-H⋯N hydrogen bond on the (1) H shielding and one-bond (13) C-(1) H coupling complicates the configurational assignment of the considered compound because of these spectral parameters. The (1) H, (13) C and (15) N chemical shifts of the 2- and 8-(CH(3) )(2) N groups attached to the -C(CH(3) )═N- and -CH═N- moieties, respectively, reveal pronounced difference. The ab initio calculations show that the 8-(CH(3) )(2) N group conjugate effectively with the π-framework, and the 2-(CH(3) )(2) N group twisted out from the plane of the backbone and loses conjugation. As a result, the degree of charge transfer from the N-2- and N-8- nitrogen lone pairs to the π-framework varies, which affects the (1) H, (13) C and (15) N shieldings. PMID:22615146

  15. CHHC and 1H-1H Magnetization Exchange: Analysis by Experimental Solid-State NMR and 11-Spin Density-Matrix Simulations

    PubMed Central

    Aluas, Mihaela; Tripon, Carmen; Griffin, John M.; Filip, Xenia; Ladizhansky, Vladimir; Griffin, Robert G.; Brown, Steven P.; Filip, Claudiu

    2009-01-01

    A protocol is presented for correcting the effect of non-specific cross polarization in CHHC solid-state MAS NMR experiments, thus allowing the recovery of the 1H-1H magnetization exchange functions from the mixing-time dependent buildup of experimental CHHC peak intensity. The presented protocol also incorporates a scaling procedure to take into account the effect of multiplicity of a CH2 or CH3 moiety. Experimental CHHC buildup curves are presented for L-Tyrosine.HCl samples where either all or only one in ten molecules are U-13C labeled. Good agreement between experiment and 11-spin SPINEVOLUTION simulation (including only isotropic 1H chemical shifts) is demonstrated for the initial buildup (tmix < 100 μs) of CHHC peak intensity corresponding to an intramolecular close (2.5 Å) H-H proximity. Differences in the initial CHHC buildup are observed between the 1 in 10 dilute and 100 % samples for cases where there is a close intermolecular H-H proximity in addition to a close intramolecular H-H proximity. For the dilute sample, CHHC cross peak intensities tended to significantly lower values for long mixing times (500 μs) as compared to the 100 % sample. This difference is explained as being due to the dependence of the limiting total magnetization on the ratio Nobs/Ntot between the number of protons that are directly attached to a 13C nucleus and hence contribute significantly to the observed 13C CHHC NMR signal, and the total number of 1H spins into the system. 1H-1H magnetization exchange curves extracted from CHHC spectra for the 100 % L-Tyrosine.HCl sample exhibit a clear sensitivity to the root sum squared dipolar coupling, with fast build-up being observed for the shortest intramolecular distances (2.5 Å) and slower, yet observable build-up for the longer intermolecular distances (up to 5 Å). PMID:19467890

  16. The complete genome sequence of the Arcobacter butzleri cattle isolate 7h1h

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arcobacter butzleri strain 7h1h was isolated in the UK from a clinically healthy dairy cow. The genome of this isolate was sequenced to completion. Here we present the annotation and analysis of the completed 7h1h genome, as well as comparison of this genome to the existing A. butzleri RM4018 and ED...

  17. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine.

    PubMed Central

    Stumvoll, M; Chintalapudi, U; Perriello, G; Welle, S; Gutierrez, O; Gerich, J

    1995-01-01

    Despite ample evidence that the kidney can both produce and use appreciable amounts of glucose, the human kidney is generally regarded as playing a minor role in glucose homeostasis. This view is based on measurements of arteriorenal vein glucose concentrations indicating little or no net release of glucose. However, inferences from net balance measurements do not take into consideration the simultaneous release and uptake of glucose by the kidney. Therefore, to assess the contribution of release and uptake of glucose by the human kidney to overall entry and removal of plasma glucose, we used a combination of balance and isotope techniques to measure renal glucose net balance, fractional extraction, uptake and release as well as overall plasma glucose appearance and disposal in 10 normal volunteers under basal postabsorptive conditions and during a 3-h epinephrine infusion. In the basal postabsorptive state, there was small but significant net output of glucose by the kidney (66 +/- 22 mumol.min-1, P = 0.016). However, since renal glucose fractional extraction averaged 2.9 +/- 0.3%, there was considerable renal glucose uptake (2.3 +/- 0.2 mumol.kg-1.min-1) which accounted for 20.2 +/- 1.7% of systemic glucose disposal (11.4 +/- 0.5 mumol.kg-1.min-1). Renal glucose release (3.2 +/- 0.2 mumol.kg-1.min-1) accounted for 27.8 +/- 2.1% of systemic glucose appearance (11.4 +/- 0.5 mumol.kg-1.min-1). Epinephrine infusion, which increased plasma epinephrine to levels observed during hypoglycemia (3722 +/- 453 pmol/liter) increased renal glucose release nearly twofold (5.2 +/- 0.5 vs 2.8 +/- 0.1 mol.kg-1.min-1, P = 0.01) so that at the end of the infusion, renal glucose release accounted for 40.3 +/- 5.5% of systemic glucose appearance and essentially all of the increase in systemic glucose appearance. These observations suggest an important role for the human kidney in glucose homeostasis. PMID:7593645

  18. A classical approach in simple nuclear fusion reaction {sub 1}H{sup 2}+{sub 1}H{sup 3} using two-dimension granular molecular dynamics model

    SciTech Connect

    Viridi, S.; Kurniadi, R.; Waris, A.; Perkasa, Y. S.

    2012-06-06

    Molecular dynamics in 2-D accompanied by granular model provides an opportunity to investigate binding between nuclei particles and its properties that arises during collision in a fusion reaction. A fully classical approach is used to observe the influence of initial angle of nucleus orientation to the product yielded by the reaction. As an example, a simplest fusion reaction between {sub 1}H{sup 2} and {sub 1}H{sup 3} is observed. Several products of the fusion reaction have been obtained, even the unreported ones, including temporary {sub 2}He{sup 4} nucleus.

  19. Blood glucose monitoring.

    PubMed

    Davey, Sarah

    2014-06-10

    I found the CPD article on blood glucose monitoring and management in acute stroke care interesting and informative. As I am a mental health nursing student, my knowledge of chronic physical conditions is limited, so I learned a lot. PMID:24894257

  20. Glucose Tolerance and Hyperkinesis.

    ERIC Educational Resources Information Center

    Langseth, Lillian; Dowd, Judith

    Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)

  1. Glucose urine test

    MedlinePlus

    ... with a color-sensitive pad. The color the dipstick changes to tells the provider the level of glucose in your urine. If needed, your provider may ask you to collect your urine at home over 24 hours . Your provider will tell you how to do ...

  2. Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance

    PubMed Central

    Xiang, Shou-Kui; Wan, Jing-Bo; Jiang, Xiao-Hong; Zhu, Yong-Hua; Ma, Jin-Hong; Hua, Fei

    2016-01-01

    Background It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). Material/Methods We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. Results During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. Conclusions Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation. PMID:27447783

  3. Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance.

    PubMed

    Xiang, Shou-Kui; Wan, Jing-Bo; Jiang, Xiao-Hong; Zhu, Yong-Hua; Ma, Jin-Hong; Hua, Fei

    2016-01-01

    BACKGROUND It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). MATERIAL AND METHODS We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. RESULTS During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. CONCLUSIONS Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation. PMID:27447783

  4. Renal Glucose Handling

    PubMed Central

    Ferrannini, Ele; Veltkamp, Stephan A.; Smulders, Ronald A.; Kadokura, Takeshi

    2013-01-01

    OBJECTIVE Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function. RESEARCH DESIGN AND METHODS Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 ± 9 years, fasting glucose 133 ± 39 mg/dL, mean ± SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 ≥90 mL · min–1 · 1.73 m−2), mild (eGFR2 ≥60 to <90), moderate (eGFR3 ≥30 to <60), or severe reduction in eGFR (eGFR4 ≤15 to <30). RESULTS Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P < 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR1 to 8 mg/min [7] in eGFR4, P < 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P < 0.0001 for both, r2 = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL/min decline in eGFR and an increase of 7 g for each 10 mg/dL increase in glucose above fasting normoglycemia. CONCLUSIONS In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment. PMID:23359360

  5. Transcriptional regulation of α1H T-type calcium channel under hypoxia.

    PubMed

    Sellak, Hassan; Zhou, Chun; Liu, Bainan; Chen, Hairu; Lincoln, Thomas M; Wu, Songwei

    2014-10-01

    The low-voltage-activated T-type Ca(2+) channels play an important role in mediating the cellular responses to altered oxygen tension. Among three T-type channel isoforms, α1G, α1H, and α1I, only α1H was found to be upregulated under hypoxia. However, mechanisms underlying such hypoxia-dependent isoform-specific gene regulation remain incompletely understood. We, therefore, studied the hypoxia-dependent transcriptional regulation of α1G and α1H gene promoters with the aim to identify the functional hypoxia-response elements (HREs). In rat pulmonary artery smooth muscle cells (PASMCs) and pheochromocytoma (PC12) cells after hypoxia (3% O2) exposure, we observed a prominent increase in α1H mRNA at 12 h along with a significant rise in α1H-mediated T-type current at 24 and 48 h. We then cloned two promoter fragments from the 5'-flanking regions of rat α1G and α1H gene, 2,000 and 3,076 bp, respectively, and inserted these fragments into a luciferase reporter vector. Transient transfection of PASMCs and PC12 cells with these recombinant constructs and subsequent luciferase assay revealed a significant increase in luciferase activity from the reporter containing the α1H, but not α1G, promoter fragment under hypoxia. Using serial deletion and point mutation analysis strategies, we identified a functional HRE at site -1,173cacgc-1,169 within the α1H promoter region. Furthermore, an electrophoretic mobility shift assay using this site as a DNA probe demonstrated an increased binding activity to nuclear protein extracts from the cells after hypoxia exposure. Taken together, these findings indicate that hypoxia-induced α1H upregulation involves binding of hypoxia-inducible factor to an HRE within the α1H promoter region. PMID:25099734

  6. Transcriptional regulation of α1H T-type calcium channel under hypoxia

    PubMed Central

    Sellak, Hassan; Zhou, Chun; Liu, Bainan; Chen, Hairu; Lincoln, Thomas M.

    2014-01-01

    The low-voltage-activated T-type Ca2+ channels play an important role in mediating the cellular responses to altered oxygen tension. Among three T-type channel isoforms, α1G, α1H, and α1I, only α1H was found to be upregulated under hypoxia. However, mechanisms underlying such hypoxia-dependent isoform-specific gene regulation remain incompletely understood. We, therefore, studied the hypoxia-dependent transcriptional regulation of α1G and α1H gene promoters with the aim to identify the functional hypoxia-response elements (HREs). In rat pulmonary artery smooth muscle cells (PASMCs) and pheochromocytoma (PC12) cells after hypoxia (3% O2) exposure, we observed a prominent increase in α1H mRNA at 12 h along with a significant rise in α1H-mediated T-type current at 24 and 48 h. We then cloned two promoter fragments from the 5′-flanking regions of rat α1G and α1H gene, 2,000 and 3,076 bp, respectively, and inserted these fragments into a luciferase reporter vector. Transient transfection of PASMCs and PC12 cells with these recombinant constructs and subsequent luciferase assay revealed a significant increase in luciferase activity from the reporter containing the α1H, but not α1G, promoter fragment under hypoxia. Using serial deletion and point mutation analysis strategies, we identified a functional HRE at site −1,173cacgc−1,169 within the α1H promoter region. Furthermore, an electrophoretic mobility shift assay using this site as a DNA probe demonstrated an increased binding activity to nuclear protein extracts from the cells after hypoxia exposure. Taken together, these findings indicate that hypoxia-induced α1H upregulation involves binding of hypoxia-inducible factor to an HRE within the α1H promoter region. PMID:25099734

  7. Correlation of salivary glucose, blood glucose and oral candidal carriage in the saliva of type 2 diabetics: A case-control study

    PubMed Central

    Kumar, Satish; Padmashree, S.; Jayalekshmi, Rema

    2014-01-01

    Objectives: To study the correlation between blood glucose levels and salivary glucose levels in type 2 diabetic patients, to study the relationship between salivary glucose levels and oral candidal carriage in type 2 diabetic patients and to determine whether salivary glucose levels could be used as a noninvasive tool for the measurement of glycemic control in type 2 diabetics. Study Design: The study population consisted of three groups: Group 1 consisted of 30 controlled diabetics and Group 2 consisted of 30 uncontrolled diabetics based on their random nonfasting plasma glucose levels. Group 3 consisted of 30 healthy controls. Two milliliters of peripheral blood was collected for the estimation of random nonfasting plasma glucose levels and glycosylated hemoglobin (HbA1c). Unstimulated saliva was collected for the estimation of salivary glucose. Saliva was collected by the oral rinse technique for the estimation of candidal counts. Results: The salivary glucose levels were significantly higher in controlled and uncontrolled diabetics when compared with controls. The salivary candidal carriage was also significantly higher in uncontrolled diabetics when compared with controlled diabetics and nondiabetic controls. The salivary glucose levels showed a significant correlation with blood glucose levels, suggesting that salivary glucose levels can be used as a monitoring tool for predicting glycemic control in diabetic patients. Conclusion: The present study found that estimation of salivary glucose levels can be used as a noninvasive, painless technique for the measurement of diabetic status of a patient in a dental set up. Increased salivary glucose levels leads to increased oral candidal carriage; therefore, oral diagnosticians are advised to screen the diabetic patients for any oral fungal infections and further management. PMID:25191065

  8. Metabolic profiling studies on the toxicological effects of realgar in rats by {sup 1}H NMR spectroscopy

    SciTech Connect

    Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing Pei Fengkui Li Weisheng; Wu Yijie

    2009-02-01

    The toxicological effects of realgar after intragastrical administration (1 g/kg body weight) were investigated over a 21 day period in male Wistar rats using metabonomic analysis of {sup 1}H NMR spectra of urine, serum and liver tissue aqueous extracts. Liver and kidney histopathology examination and serum clinical chemistry analyses were also performed. {sup 1}H NMR spectra and pattern recognition analyses from realgar treated animals showed increased excretion of urinary Kreb's cycle intermediates, increased levels of ketone bodies in urine and serum, and decreased levels of hepatic glucose and glycogen, as well as hypoglycemia and hyperlipoidemia, suggesting the perturbation of energy metabolism. Elevated levels of choline containing metabolites and betaine in serum and liver tissue aqueous extracts and increased serum creatine indicated altered transmethylation. Decreased urinary levels of trimethylamine-N-oxide, phenylacetylglycine and hippurate suggested the effects on the gut microflora environment by realgar. Signs of impairment of amino acid metabolism were supported by increased hepatic glutamate levels, increased methionine and decreased alanine levels in serum, and hypertaurinuria. The observed increase in glutathione in liver tissue aqueous extracts could be a biomarker of realgar induced oxidative injury. Serum clinical chemistry analyses showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. The time-dependent biochemical variations induced by realgar were achieved using pattern recognition methods. This work illustrated the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by traditional Chinese medicine.

  9. Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit

    PubMed Central

    Modesto-Alapont, Vicente; Gonzalez-Marrachelli, Vannina; Vento-Rehues, Rosa; Jorda-Miñana, Angela; Blanquer-Olivas, Jose; Monleon, Daniel

    2015-01-01

    Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by 1H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a 1H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA. PMID:26565633

  10. Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional (1)H-MRS study.

    PubMed

    Reyngoudt, Harmen; Paemeleire, Koen; Dierickx, Anneloor; Descamps, Benedicte; Vandemaele, Pieter; De Deene, Yves; Achten, Eric

    2011-06-01

    Proton magnetic resonance spectroscopy ((1)H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS ((31)P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional (1)H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1-0.2 μmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients. PMID:21301922

  11. Dysregulation of Glucose Homeostasis Following Chronic Exogenous Administration of Leptin in Healthy Sprague-Dawley Rats

    PubMed Central

    Wjidan, Khalil; Ibrahim, Effendi; Caszo, Brinnell; Gnanou, Justin

    2015-01-01

    Introduction Impaired glucose utilization is seen in chronic hyperleptinaemia associated conditions such as obesity and type 2 diabetes mellitus. It is unclear if this impaired glucose utilization is due to the effect of persistent hyperleptinaemia on insulin secretion from the beta cells of pancreas. Aim To examine the effects of chronic leptin administration on plasma glucose regulation in rats. Materials and Methods Glucose challenge curves were plotted for male Sprague-Dawley rats treated with either normal saline (Control; n=8) or subcutaneous leptin injection for 42 days (60 μg/kg body weight/day; n=8). Plasma glucose and plasma insulin levels were measured at 0, 5, 10, 15, 20 and 25 minutes after glucose challenege. Skeletal muscle tissue was collected at the end of a glucose challenge for glucose transporter-4 protein content, insulin receptor and glucose transporter-4 mRNA expression. Data were analysed using repeated measures and one-way ANOVA with post-hoc analysis. Results Chronic leptin treatment caused significantly higher fasting insulin level. Post glucose challenge, there was a significant increase in blood glucose levels and insulin level in the leptin treated rats. There was no significant difference in the skeletal muscle glucose transporter-4 content. However, leptin treated rats showed decreased mRNA expression of Insulin Receptor and glucose transporter-4 in the skeletal muscle. Conclusion Leptin administration for 42 days caused hyperinsulinaemia and decreased the expression of insulin receptors in insulin sensitive tissues leading to the development of an insulin resistance-like state in the rats. PMID:26816939

  12. Tracing bacterial metabolism using multi-nuclear (1H, 2H, and 13C) Solid State NMR: Realizing an Idea Initiated by James Scott

    NASA Astrophysics Data System (ADS)

    Cody, G.; Fogel, M. L.; Jin, K.; Griffen, P.; Steele, A.; Wang, Y.

    2011-12-01

    Approximately 6 years ago, while at the Geophysical Laboratory, James Scott became interested in the application of Solid State Nuclear Magnetic Resonance Spectroscopy to study bacterial metabolism. As often happens, other experiments intervened and the NMR experiments were not pursued. We have revisited Jame's question and find that using a multi-nuclear approach (1H, 2H, and 13C Solid State NMR) on laboratory cell culture has some distinct advantages. Our experiments involved batch cultures of E. coli (MG1655) harvested at stationary phase. In all experiments the growth medium consisted of MOPS medium for enterobacteria, where the substrate is glucose. In one set of experiments, 10 % of the water was D2O; in another 10 % of the glucose was per-deuterated. The control experiment used both water and glucose at natural isotopic abundance. A kill control of dead E. coli immersed in pure D2O for an extended period exhibited no deuterium incorporation. In both deuterium enriched experiments, considerable incorporation of deuterium into E. coli's biomolecular constituents was detected via 2H Solid State NMR. In the case of the D2O enriched experiment, 58 % of the incorporated deuterium is observed in a sharp peak at a frequency of 0.31 ppm, consistent with D incorporation in the cell membrane lipids, the remainder is observed in a broad peak at a higher frequency (centered at 5.4 ppm, but spanning out to beyond 10 ppm) that is consistent with D incorporation into predominantly DNA and RNA. In the case of the D-glucose experiments, 61 % of the deuterium is observed in a sharp resonance peak at 0.34 ppm, also consistent with D incorporation into membrane lipids, the remainder of the D is observed at a broad resonance peak centered at 4.3 ppm, consistent with D enrichment in glycogen. Deuterium abundance in the E. coli cells grown in 10 % D2O is nearly 2X greater than that grown with 10 % D-glucose. Very subtle differences are observed in both the 1H and 13C solid

  13. Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics

    PubMed Central

    Coelho, Margarida; Nunes, Patricia; Mendes, Vera M.; Manadas, Bruno; Heerschap, Arend; Jones, John G.

    2015-01-01

    Mice deficient in adipose triglyceride lipase (ATGL−/−) present elevated ectopic lipid levels but are paradoxically glucose-tolerant. Measurement of endogenous glucose production (EGP) and Cori cycle activity provide insights into the maintenance of glycemic control in these animals. These parameters were determined in 7 wild-type (ATGL+/−) and 6 ATGL−/− mice by a primed-infusion of [U-13C6]glucose followed by LC-MS/MS targeted mass-isotopomer analysis of blood glucose. EGP was quantified by isotope dilution of [U-13C6]glucose while Cori cycling was estimated by analysis of glucose triose 13C-isotopomers. Fasting plasma free fatty-acids were significantly lower in ATGL−/− versus control mice (0.43 ± 0.05 mM versus 0.73 ± 0.11 mM, P < 0.05). Six-hour fasting EGP rates were identical for both ATGL−/− and control mice (79 ± 11 versus 71 ± 7 μmol/kg/min, resp.). Peripheral glucose metabolism was dominated by Cori cycling (80 ± 2% and 82 ± 7% of glucose disposal for ATGL−/− and control mice, resp.) indicating that peripheral glucose oxidation was not significantly upregulated in ATGL−/− mice under these conditions. The glucose 13C-isotopomer distributions in both ATGL−/− and control mice were consistent with extensive hepatic pyruvate recycling. This suggests that gluconeogenic outflow from the Krebs cycle was also well compensated in ATGL−/− mice. PMID:26236747

  14. The Correlation of Hemoglobin A1c to Blood Glucose

    PubMed Central

    Sikaris, Ken

    2009-01-01

    The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of “average blood glucose” as though “blood glucose” were itself a simple idea. When we consider all the blood glucose forms—arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting—we can start to see that this is not a simple issue. Nevertheless, it seems as though HbA1c correlates to any single glucose measurement. Having more than one measurement and taking those measurements in the preceding month improves the correlation further. In particular, by having glucose measurements that reflect both the relatively lower overnight glucose levels and measurements that reflect the postprandial peaks improves not only our ability to manage diabetes patients, but also our understanding of how HbA1c levels are determined. Modern continuous glucose monitoring (CGM) devices may take thousands of glucose results over a week. Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c. The ability to relate HbA1c to average glucose may become a popular method for reporting HbA1c, eliminating current concerns regarding differences in HbA1c standardization. Hemoglobin A1c expressed as an average glucose may be more understandable to patients and improve not only their understanding, but also their ability to improve their diabetes management. PMID:20144279

  15. Glucose Metabolism in Neisseria gonorrhoeae

    PubMed Central

    Morse, Stephen A.; Stein, Stefanie; Hines, James

    1974-01-01

    The metabolism of glucose was examined in several clinical isolates of Neisseria gonorrhoeae. Radiorespirometric studies revealed that growing cells metabolized glucose by a combination on the Entner-Doudoroff and pentose phosphate pathways. A portion of the glyceraldehyde-3-phosphate formed via the Entner-Doudoroff pathway was recycled by conversion to glucose-6-phosphate. Subsequent catabolism of this glucose-6-phosphate by either the Entner-Doudoroff or pentose phosphate pathways yielded CO2 from the original C6 of glucose. Enzyme analyses confirmed the presence of all enzymes of the Entner-Doudoroff, pentose phosphate, and Embden-Meyerhof-Parnas pathways. There was always a high specific activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) relative to that of 6-phosphogluconate dehydrogenase (EC 1.1.1.44). The glucose-6-phosphate dehydrogenase utilized either nicotinamide adenine dinucleotide phosphate or nicotinamide adenine dinucleotide as electron acceptor. Acetate was the only detectable nongaseous end product of glucose metabolism. Following the disappearance of glucose, acetate was metabolized by the tricarboxylic acid cycle as evidenced by the preferential oxidation of [1-14C]acetate over that of [2-14C]acetate. When an aerobically grown log-phase culture was subjected to anaerobic conditions, lactate and acetate were formed from glucose. Radiorespirometric studies showed that under these conditions, glucose was dissimilated entirely by the Entner-Doudoroff pathway. Further studies determined that this anaerobic dissimilation of glucose was not growth dependent. PMID:4156358

  16. 2D 1H and 3D 1H-15N NMR of zinc-rubredoxins: contributions of the beta-sheet to thermostability.

    PubMed Central

    Richie, K. A.; Teng, Q.; Elkin, C. J.; Kurtz, D. M.

    1996-01-01

    Based on 2D 1H-1H and 2D and 3D 1H-15N NMR spectroscopies, complete 1H NMR assignments are reported for zinc-containing Clostridium pasteurianum rubredoxin (Cp ZnRd). Complete 1H NMR assignments are also reported for a mutated Cp ZnRd, in which residues near the N-terminus, namely, Met 1, Lys 2, and Pro 15, have been changed to their counterparts, (-), Ala and Glu, respectively, in rubredoxin from the hyperthermophilic archaeon, Pyrococcus furiosus (Pf Rd). The secondary structure of both wild-type and mutated Cp ZnRds, as determined by NMR methods, is essentially the same. However, the NMR data indicate an extension of the three-stranded beta-sheet in the mutated Cp ZnRd to include the N-terminal Ala residue and Glu 15, as occurs in Pf Rd. The mutated Cp Rd also shows more intense NOE cross peaks, indicating stronger interactions between the strands of the beta-sheet and, in fact, throughout the mutated Rd. However, these stronger interactions do not lead to any significant increase in thermostability, and both the mutated and wild-type Cp Rds are much less thermostable than Pf Rd. These correlations strongly suggest that, contrary to a previous proposal [Blake PR et al., 1992, Protein Sci 1:1508-1521], the thermostabilization mechanism of Pf Rd is not dominated by a unique set of hydrogen bonds or electrostatic interactions involving the N-terminal strand of the beta-sheet. The NMR results also suggest that an overall tighter protein structure does not necessarily lead to increased thermostability. PMID:8732760

  17. Ceramide 1-phosphate stimulates glucose uptake in macrophages

    PubMed Central

    Ouro, Alberto; Arana, Lide; Gangoiti, Patricia; Rivera, Io-Guané; Ordoñez, Marta; Trueba, Miguel; Lankalapalli, Ravi S.; Bittman, Robert; Gomez-Muñoz, Antonio

    2014-01-01

    It is well established that ceramide 1-phosphate (C1P) is mitogenic and antiapoptotic, and that it is implicated in the regulation of macrophage migration. These activities require high energy levels to be available in cells. Macrophages obtain most of their energy from glucose. In this work, we demonstrate that C1P enhances glucose uptake in RAW264.7 macrophages. The major glucose transporter involved in this action was found to be GLUT 3, as determined by measuring its translocation from the cytosol to the plasma membrane. C1P-stimulated glucose uptake was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3K) or Akt, also known as protein kinase B (PKB), and by specific siRNAs to silence the genes encoding for these kinases. C1P-stimulated glucose uptake was also inhibited by pertussis toxin (PTX) and by the siRNA that inhibited GLUT 3 expression. C1P increased the affinity of the glucose transporter for its substrate, and enhanced glucose metabolism to produce ATP. The latter action was also inhibited by PI3K- and Akt-selective inhibitors, PTX, or by specific siRNAs to inhibit GLUT 3 expression. PMID:23333242

  18. Effect of high glucose concentrations on human erythrocytes in vitro

    PubMed Central

    Viskupicova, Jana; Blaskovic, Dusan; Galiniak, Sabina; Soszyński, Mirosław; Bartosz, Grzegorz; Horakova, Lubica; Sadowska-Bartosz, Izabela

    2015-01-01

    Exposure to high glucose concentrations in vitro is often employed as a model for understanding erythrocyte modifications in diabetes. However, effects of such experiments may be affected by glucose consumption during prolonged incubation and changes of cellular parameters conditioned by impaired energy balance. The aim of this study was to compare alterations in various red cell parameters in this type of experiment to differentiate between those affected by glycoxidation and those affected by energy imbalance. Erythrocytes were incubated with 5, 45 or 100 mM glucose for up to 72 h. High glucose concentrations intensified lipid peroxidation and loss of activities of erythrocyte enzymes (glutathione S-transferase and glutathione reductase). On the other hand, hemolysis, eryptosis, calcium accumulation, loss of glutathione and increase in the GSSG/GSH ratio were attenuated by high glucose apparently due to maintenance of energy supply to the cells. Loss of plasma membrane Ca2+-ATPase activity and decrease in superoxide production were not affected by glucose concentration, being seemingly determined by processes independent of both glycoxidation and energy depletion. These results point to the necessity of careful interpretation of data obtained in experiments, in which erythrocytes are subject to treatment with high glucose concentrations in vitro. PMID:26141922

  19. Intermolecular Interactions between Eosin Y and Caffeine Using (1)H-NMR Spectroscopy.

    PubMed

    Okuom, Macduff O; Wilson, Mark V; Jackson, Abby; Holmes, Andrea E

    2013-12-31

    DETECHIP has been used in testing analytes including caffeine, cocaine, and tetrahydrocannabinol (THC) from marijuana, as well as date rape and club drugs such as flunitrazepam, gamma-hydroxybutyric acid (GHB), and methamphetamine. This study investigates the intermolecular interaction between DETECHIP sensor eosin Y (DC1) and the analyte (caffeine) that is responsible for the fluorescence and color changes observed in the actual array. Using (1)H-NMR, (1)H-COSY, and (1)H-DOSY NMR methods, a proton exchange from C-8 of caffeine to eosin Y is proposed. PMID:25018772

  20. Intermolecular Interactions between Eosin Y and Caffeine Using 1H-NMR Spectroscopy

    PubMed Central

    Okuom, Macduff O.; Wilson, Mark V.; Jackson, Abby; Holmes, Andrea E.

    2014-01-01

    DETECHIP has been used in testing analytes including caffeine, cocaine, and tetrahydrocannabinol (THC) from marijuana, as well as date rape and club drugs such as flunitrazepam, gamma-hydroxybutyric acid (GHB), and methamphetamine. This study investigates the intermolecular interaction between DETECHIP sensor eosin Y (DC1) and the analyte (caffeine) that is responsible for the fluorescence and color changes observed in the actual array. Using 1H-NMR, 1H-COSY, and 1H-DOSY NMR methods, a proton exchange from C-8 of caffeine to eosin Y is proposed. PMID:25018772

  1. Downregulation of mouse intestinal Na(+)-coupled glucose transporter SGLT1 by gum arabic (Acacia Senegal).

    PubMed

    Nasir, Omaima; Artunc, Ferruh; Wang, Kan; Rexhepaj, Rexhep; Föller, Michael; Ebrahim, Ammar; Kempe, Daniela S; Biswas, Raja; Bhandaru, Madhuri; Walter, Michael; Mohebbi, Nilufar; Wagner, Carsten A; Saeed, Amal M; Lang, Florian

    2010-01-01

    Intestinal Na(+)-coupled glucose transporter SGLT1 determines the rate of glucose transport, which in turn influences glucose-induced insulin release and development of obesity. The present study explored effects of Gum Arabic (GA), a dietary polysaccharide from dried exudates of Acacia Senegal, on intestinal glucose transport and body weight in wild-type C57Bl/6 mice. Treatment with GA (100 g/l) in drinking water for four weeks did not affect intestinal SGLT1 transcript levels but decreased SGLT1 protein abundance in jejunal brush border membrane vesicles. Glucose-induced jejunal short-circuit currents revealed that GA treatment decreased electrogenic glucose transport. Drinking a 20% glucose solution for four weeks significantly increased body weight and fasting plasma glucose concentrations, effects significantly blunted by simultaneous treatment with GA. GA further significantly blunted the increase in body weight, fasting plasma glucose and fasting insulin concentrations during high fat diet. In conclusion, the present observations disclose a completely novel effect of gum arabic, i.e. its ability to decrease intestinal SGLT1 expression and activity and thus to counteract glucose-induced obesity. PMID:20110681

  2. Glucose and Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2008-04-01

    When a human's enzymes attach glucose to proteins they do so at specific sites on a specific molecule for a specific purpose that also can include ascorbic acid (AA) at a high level such as 1 gram per hour during exposure. In an AA synthesizing animal the manifold increase of AA produced in response to illness is automatic. In contrast, the human non-enzymatic process adds glucose haphazardly to any number of sites along available peptide chains. As Cerami clarified decades ago, extensive crosslinking of proteins contributes to loss of elasticity in aging tissues. Ascorbic acid reduces the random non-enyzmatic glycation of proteins. Moreover, AA is a cofactor for hydroxylase enzymes that are necessary for the production and replacement of collagen and other structural proteins. We will discuss the relevance of ``aging is scurvy'' to the biochemistry of human aging.

  3. Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study

    PubMed Central

    Sati, Jasmine; Mohanty, Biraja Prasad; Garg, Mohan Lal; Koul, Ashwani

    2016-01-01

    Silibinin, a major bioactive flavonolignan in Silybum marianum, has received considerable attention in view of its anticarcinogenic activity. The present study examines its anticancer potential against 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin cancer. Male LACA mice were randomly segregated into 4 groups: Control, DMBA/TPA, Silibinin and Silibinin+DMBA/TPA. Tumors in DMBA/TPA and Silibinin+DMBA/TPA groups were histologically graded as squamous cell carcinoma. In the Silibinin+DMBA/TPA group, significant reduction in tumor incidence (23%), tumor volume (64.4%), and tumor burden (84.8%) was observed when compared to the DMBA/TPA group. The underlying protective mechanism of Silibinin action was studied at pre-initiation (2 weeks), post-initiation (10 weeks) and promotion (22 weeks) stages of the skin carcinogenesis. The antioxidant nature of Silibinin was evident at the end of 2 weeks of its treatment. However, towards the end of 10 and 22 weeks, elevated lipid peroxidation (LPO) levels indicate the pro-oxidative nature of Silibinin in the cancerous tissue. TUNEL assay revealed enhanced apoptosis in the Silibinin+DMBA/TPA group with respect to the DMBA/TPA group. Therefore, it may be suggested that raised LPO could be responsible for triggering apoptosis in the Silibinin+DMBA/TPA group. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the metabolic profile of the skin /skin tumors. Dimethylamine (DMA), glycerophosphocholine (GPC), glucose, lactic acid, taurine and guanine were identified as the major contributors for separation between the groups from the Principal Component Analysis (PCA) of the metabolite data. Enhanced DMA levels with no alteration in GPC, glucose and lactate levels reflect altered choline metabolism with no marked Warburg effect in skin tumors. However, elevated guanine levels with potent suppression of taurine and glucose levels in the Silibinin+DMBA/TPA group are

  4. Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study.

    PubMed

    Sati, Jasmine; Mohanty, Biraja Prasad; Garg, Mohan Lal; Koul, Ashwani

    2016-01-01

    Silibinin, a major bioactive flavonolignan in Silybum marianum, has received considerable attention in view of its anticarcinogenic activity. The present study examines its anticancer potential against 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin cancer. Male LACA mice were randomly segregated into 4 groups: Control, DMBA/TPA, Silibinin and Silibinin+DMBA/TPA. Tumors in DMBA/TPA and Silibinin+DMBA/TPA groups were histologically graded as squamous cell carcinoma. In the Silibinin+DMBA/TPA group, significant reduction in tumor incidence (23%), tumor volume (64.4%), and tumor burden (84.8%) was observed when compared to the DMBA/TPA group. The underlying protective mechanism of Silibinin action was studied at pre-initiation (2 weeks), post-initiation (10 weeks) and promotion (22 weeks) stages of the skin carcinogenesis. The antioxidant nature of Silibinin was evident at the end of 2 weeks of its treatment. However, towards the end of 10 and 22 weeks, elevated lipid peroxidation (LPO) levels indicate the pro-oxidative nature of Silibinin in the cancerous tissue. TUNEL assay revealed enhanced apoptosis in the Silibinin+DMBA/TPA group with respect to the DMBA/TPA group. Therefore, it may be suggested that raised LPO could be responsible for triggering apoptosis in the Silibinin+DMBA/TPA group. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the metabolic profile of the skin /skin tumors. Dimethylamine (DMA), glycerophosphocholine (GPC), glucose, lactic acid, taurine and guanine were identified as the major contributors for separation between the groups from the Principal Component Analysis (PCA) of the metabolite data. Enhanced DMA levels with no alteration in GPC, glucose and lactate levels reflect altered choline metabolism with no marked Warburg effect in skin tumors. However, elevated guanine levels with potent suppression of taurine and glucose levels in the Silibinin+DMBA/TPA group are

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

    SciTech Connect

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

    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 dephosphorylation 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.

  6. Glucose-6-phosphate isomerase.

    PubMed

    Achari, A; Marshall, S E; Muirhead, H; Palmieri, R H; Noltmann, E A

    1981-06-26

    Glucose-6-phosphate isomerase (EC 5.3.1.9) is a dimeric enzyme of molecular mass 132000 which catalyses the interconversion of D-glucose-6-phosphate and D-fructose-6-phosphate. The crystal structure of the enzyme from pig muscle has been determined at a nominal resolution of 2.6 A. The structure is of the alpha/beta type. Each subunit consists of two domains and the active site is in both the domain interface and the subunit interface (P.J. Shaw & H. Muirhead (1976), FEBS Lett. 65, 50-55). Each subunit contains 13 methionine residues so that cyanogen bromide cleavage will produce 14 fragments, most of which have been identified and at least partly purified. Sequence information is given for about one-third of the molecule from 5 cyanogen bromide fragments. One of the sequences includes a modified lysine residue. Modification of this residue leads to a parallel loss of enzymatic activity. A tentative fit of two of the peptides to the electron density map has been made. It seems possible that glucose-6-phosphate isomerase, triose phosphate isomerase and pyruvate kinase all contain a histidine and a glutamate residue at the active site. PMID:6115414

  7. Characterisation of the 1H and 13C NMR spectra of methylcitric acid

    NASA Astrophysics Data System (ADS)

    Krawczyk, Hanna; Martyniuk, Tomasz

    2007-06-01

    Methylcitric acid (MCA) was synthesised in Reformatsky reaction (2 RS, 3 RS stereoisomers) and in the nucleophilic addition (2 RS, 3 SR stereoisomers). The stereoselectivity of these reactions was analysed. 1H and 13C NMR spectra of diastereoisomers of methylcitric acid were recorded and interpreted. The values of 1H chemical shifts and 1H- 1H coupling constants were analysed. Proton-decoupled high-resolution 13C NMR spectra of MCA diastereoisomers were measured in a series of dilute water solutions of various acidities. These data may provide a basis for unequivocal determination of the presence of MCA in the urine samples of patients' suffering from propionic acidemia, methylmalonic aciduria, or holocarboxylase synthetase deficiency. NMR spectroscopy enables determination of MCA diastereoisomers in body fluids and can be a complementary and useful diagnostic tool.

  8. Regioselectively Controlled Synthesis of N-Substituted (Trifluoromethyl)pyrimidin-2(1H)-ones.

    PubMed

    da Silva, Andreia M P W; da Silva, Fabio M; Bonacorso, Helio G; Frizzo, Clarissa P; Martins, Marcos A P; Zanatta, Nilo

    2016-05-01

    A simple and regioselectively controlled method for the preparation of both 1,4- and 1,6-regioisomers of 1-substituted 4(6)-trifluoromethyl-pyrimidin-2(1H)-ones is described. Both regioisomers were synthesized from the cyclocondensation reaction of 4-substituted 1,1,1-trifluoro-4-methoxybut-3-en-2-ones: with nonsymmetric ureas for the 1-substituted 4-(trifluoromethyl)pyrimidin-2(1H)-ones (1,4-isomer) and with nonsymmetric 1-substituted 2-methylisothiourea sulfates for the synthesis of 1-substituted 6-(trifluoromethyl)pyrimidin-2(1H)-ones (1,6-isomer). Each method furnished only the respective isomer in very good yields. The structure of the products was assigned based on the (1)H and (13)C NMR as well as 2D HMBC spectral analysis. PMID:27070191

  9. Lemna minor L. as a model organism for ecotoxicological studies performing 1H NMR fingerprinting.

    PubMed

    Aliferis, Konstantinos A; Materzok, Sylwia; Paziotou, Georgia N; Chrysayi-Tokousbalides, Maria

    2009-08-01

    A validated method applying (1)H NMR fingerprinting for the study of metabolic changes caused in Lemna minor L. by various phytotoxic substances is presented. (1)H NMR spectra of crude extracts from untreated and treated colonies with the herbicides glyphosate, mesotrione, norflurazon, paraquat and the phytotoxin pyrenophorol were subjected to multivariate analyses for detecting differences between groups of treatments. Partial least squares-discriminant analysis (PLS-DA) and hierarchical cluster analysis (HCA) were carried out in order to discriminate and classify treatments according to the observed changes in the metabolome of the plant. Although the compounds at the concentrations used did not cause macroscopically observable symptoms of phytotoxicity, characteristic metabolic changes were detectable by analyzing (1)H NMR spectra. Analyses results revealed that metabonomics applying (1)H NMR fingerprinting is a potential method for the investigation of toxicological effects of xenobiotics on L. minor, and possibly on other duckweed species, helping in the understanding of such interactions. PMID:19443011

  10. Glycemic Effects of Rebaudioside A and Erythritol in People with Glucose Intolerance

    PubMed Central

    Shin, Dong Hee; Lee, Ji Hye; Kang, Myung Shin; Kim, Tae Hoon; Jeong, Su Jin; Kim, Sang Soo

    2016-01-01

    Background Rebaudioside A and erythritol are nonnutritive sweeteners. There have been several studies of their glycemic effects, but the outcomes remain controversial. The purpose of this study was to evaluate the glycemic effects of rebaudioside A and erythritol as a sweetener in people with glucose intolerance. Methods This trial evaluated the glycemic effect after 2 weeks of consumption of rebaudioside A and erythritol as sweeteners in a pre-diabetic population. The patients were evaluated for fructosamine, fasting plasma glucose, C-peptide, insulin, and 2-hour plasma glucose before and after consumption of sweetener. The primary outcome was a change in fructosamine levels from the baseline to the end of treatment. Secondary outcomes were the changes in levels of fasting plasma glucose and 2-hour plasma glucose. Results From the baseline to the end of experiment, the changes in fructosamine levels after consumption of rebaudioside A and erythritol, did not differ significantly (244.00±19.57 vs. 241.68±23.39 µmol/L, P=0.366). The change in levels from the baseline to end of the study for rebaudioside A and erythritol were fasting plasma glucose (102.56±10.72 vs. 101.32±9.20 mg/dL), 2-hour plasma glucose (154.92±54.53 vs. 141.92±42.22 mg/dL), insulin (7.56±4.29 vs. 7.20±5.12 IU/mL), and C-peptide (2.92±1.61 vs. 2.73±1.31 ng/mL), respectively, and also did not differ significantly (P>0.05 for all). Conclusion Our study suggests that consumption of rebaudioside A and erythritol does not alter the glucose homeostasis in people with glucose intolerance. PMID:27352150

  11. The Tuberous Sclerosis Complex Regulates Trafficking of Glucose Transporters and Glucose Uptake

    PubMed Central

    Jiang, Xiuyun; Kenerson, Heidi; Aicher, Lauri; Miyaoka, Robert; Eary, Janet; Bissler, John; Yeung, Raymond S.

    2008-01-01

    Human cancers often display an avidity for glucose, a feature that is exploited in clinical staging and response monitoring by using 18F-fluoro-deoxyglucose (FDG) positron emission tomography. Determinants of FDG accumulation include tumor blood flow, glucose transport, and glycolytic rate, but the underlying molecular mechanisms are incompletely understood. The phosphoinositide-3 kinase/Akt/mammalian target of rapamycin complex (mTORC) 1 pathway has been implicated in this process via the hypoxia-inducible factor alpha-dependent expression of vascular endothelial growth factor and glycolytic enzymes. Thus, we predicted that tumors with elevated mTORC1 activity would be accompanied by high FDG uptake. We tested this hypothesis in eight renal angiomyolipomas in which the loss of tuberous sclerosis complex (TSC) 1/2 function gave rise to constitutive mTORC1 activation. Surprisingly, these tumors displayed low FDG uptake on positron emission tomography. Exploring the underlying mechanisms in vitro revealed that Tsc2 regulates the membrane localization of the glucose transporter proteins (Glut)1, Glut2, an