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Sample records for improves oral glucose

  1. Improved high-fat diet-induced glucose intolerance by an oral administration of phytosphingosine.

    PubMed

    Murakami, Itsuo; Mitsutake, Susumu; Kobayashi, Naoyuki; Matsuda, Junko; Suzuki, Akemi; Shigyo, Tatsuro; Igarashi, Yasuyuki

    2013-01-01

    We have previously reported that phytoceramide and phytosphingosine (PHS) stimulated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ) in cells. PPARγ is a therapeutic target for type 2 diabetes. We found in this study that an oral administration of PHS improved diet-induced glucose intolerance in mice. Since PHS is highly expressed in yeast, PHS in fermented foods may improve diabetes.

  2. Sitagliptin improves glycaemic excursion after a meal or after an oral glucose load in Japanese subjects with impaired glucose tolerance.

    PubMed

    Kaku, K; Kadowaki, T; Terauchi, Y; Okamoto, T; Sato, A; Okuyama, K; Arjona Ferreira, J C; Goldstein, B J

    2015-11-01

    To evaluate the efficacy and tolerability of sitagliptin in subjects with impaired glucose tolerance (IGT). In a double-blind, parallel-group study, 242 Japanese subjects with IGT, determined by a 75-g oral glucose tolerance test (OGTT) at week -1, were randomized (1 : 1 : 1) to placebo (n = 83), sitagliptin 25 mg (n = 82) or 50 mg (n = 77) once daily for 8 weeks. Glycaemic variables were assessed using another OGTT at week 7 and meal tolerance tests (MTTs) at weeks 0 and 8. Primary and secondary endpoints were percent change from baseline in glucose total area under the curve 0-2 h (AUC(0 -2 h)) during the MTT and OGTT, respectively. Least squares mean percent change from baseline in glucose AUC(0 -2 h) during the MTT were -2.4, -9.5 and -11.5%, and during the OGTT were -3.7, -21.4 and -20.1% with placebo, sitagliptin 25 mg once daily, and 50 mg once daily, respectively (p < 0.001 for either sitagliptin dose vs placebo in both tests). Sitagliptin treatment enhanced early insulin response during the OGTT and decreased total insulin response, assessed as the total AUC(0 -2 h) during the MTT. Sitagliptin treatment also suppressed glucagon response during the MTT. The incidence of adverse events, including hypoglycaemia, was low and generally similar in all treatment groups. Treatment with sitagliptin significantly reduced glucose excursions during both an MTT and an OGTT; this effect was associated with an increase in early insulin secretion after oral glucose loading as well as a blunted glucagon response during an MTT. Sitagliptin was generally well tolerated in subjects with IGT. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  3. A single dose of sodium nitrate does not improve oral glucose tolerance in patients with type 2 diabetes mellitus.

    PubMed

    Cermak, Naomi M; Hansen, Dominique; Kouw, Imre W K; van Dijk, Jan-Willem; Blackwell, Jamie R; Jones, Andrew M; Gibala, Martin J; van Loon, Luc J C

    2015-08-01

    Dietary nitrate (NO3(-)) supplementation has been proposed as an emerging treatment strategy for type 2 diabetes. We hypothesized that ingestion of a single bolus of dietary NO3(-) ingestion improves oral glucose tolerance in patients with type 2 diabetes. Seventeen men with type 2 diabetes (glycated hemoglobin, 7.3% ± 0.2%) participated in a randomized crossover experiment. The subjects ingested a glucose beverage 2.5 hours after consumption of either sodium NO3(-) (0.15 mmol NaNO3(-) · kg(-1)) or a placebo solution. Venous blood samples were collected before ingestion of the glucose beverage and every 30 minutes thereafter during a 2-hour period to assess postprandial plasma glucose and insulin concentrations. The results show that plasma NO3(-) and nitrite levels were increased after NaNO3(-) as opposed to placebo ingestion (treatment-effect, P = .001). Despite the elevated plasma NO3(-) and nitrite levels, ingestion of NaNO3(-) did not attenuate the postprandial rise in plasma glucose and insulin concentrations (time × treatment interaction, P = .41 for glucose, P = .93 for insulin). Despite the lack of effect on oral glucose tolerance, basal plasma glucose concentrations measured 2.5 hours after NaNO3(-) ingestion were lower when compared with the placebo treatment (7.5 ± 0.4 vs 8.3 ± 0.4 mmol/L, respectively; P = .04). We conclude that ingestion of a single dose of dietary NO3(-) does not improve subsequent oral glucose tolerance in patients with type 2 diabetes.

  4. Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats.

    PubMed

    Higuchi, Noriyuki; Hira, Tohru; Yamada, Nao; Hara, Hiroshi

    2013-09-01

    We have previously demonstrated that ileal administration of the dietary protein hydrolysate prepared from corn zein (ZeinH) stimulated glucagon-like peptide-1 (GLP-1) secretion and attenuated hyperglycemia in rats. In this study, to examine whether oral administration of ZeinH improves glucose tolerance by stimulating GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion, glucose tolerance tests were performed in normal Sprague-Dawley male rats and diabetic Goto-Kakizaki (GK) male rats. The test solution was gavaged before ip glucose injection in normal rats or gavaged together with glucose in GK rats. Blood samples were collected from the tail vein or by using the jugular catheter to measure glucose, insulin, GLP-1, and GIP levels. In the ip glucose tolerance test, oral administration of ZeinH (2 g/kg) significantly suppressed the glycemic response accompanied by an immediate increase in plasma GLP-1 and GIP levels in normal rats. In contrast, oral administration of another dietary peptide, meat hydrolysate, did not elicit a similar effect. The glucose-lowering effect of ZeinH was attenuated by a GLP-1 receptor antagonist or by a GIP receptor antagonist. Furthermore, oral ZeinH induced GLP-1 secretion and reduced glycemic response in GK rats under the oral glucose tolerance test. These results indicate that the oral administration of the dietary peptide ZeinH improves glucose tolerance in normal and diabetic rats by its incretin-releasing activity, namely, the incretinotropic effect.

  5. Monitoring breath during oral glucose tolerance tests.

    PubMed

    Ghimenti, S; Tabucchi, S; Lomonaco, T; Di Francesco, F; Fuoco, R; Onor, M; Lenzi, S; Trivella, M G

    2013-03-01

    The evolution of breath composition during oral glucose tolerance tests (OGTTs) was analysed by thermal desorption/gas chromatography/mass spectrometry in 16 subjects and correlated to blood glucose levels. The glucose tolerance tests classified five of the subjects as diabetics, eight as affected by impaired glucose tolerance and three as normoglycaemic. Acetone levels were generally higher in diabetics (average concentration values: diabetics, 300 ± 40 ppbv; impaired glucose tolerance, 350 ± 30 ppbv; normoglycaemic, 230 ± 20 ppbv) but the large inter-individual variability did not allow us to identify the three groups by this parameter alone. The exhalation of 3-hydroxy-butan-2-one and butane-2,3-dione, likely due to the metabolization of glucose by bacteria in the mouth, was also observed. Future work will involve the extension of the analyses to other volatile compounds by attempting to improve the level of discrimination between the various classes of subjects.

  6. Oral tungstate treatment improves only transiently alteration of glucose metabolism in a new rat model of type 2 diabetes.

    PubMed

    Fierabracci, Vanna; De Tata, Vincenzo; Pocai, Alessandro; Novelli, Michela; Barberà, Albert; Masiello, Pellegrino

    2002-11-01

    It has been shown that tungstate is an effective hypoglycemic agent in several animal models of diabetes. In this study, we examined the effectiveness of oral tungstate treatment in a new experimental diabetic syndrome, induced by streptozotocin (STZ) and nicotinamide in adult rats, that shares several features with human type 2 diabetes. Sodium tungstate was administered in the drinking water (2 mg/mL) of control and diabetic rats for 15, 30, 60, and 90 d. Glucose metabolism was explored in vivo by intravenous glucose tolerance test. Insulin secretion and action were assessed in vitro in the isolated perfused pancreas and isolated adipocytes, respectively. Two weeks of tungstate treatment did not modify the moderate hyperglycemia of diabetic rats but reduced their intolerance to glucose, owing to an enhancement of postloading insulin secretion. However, this effect was transient, since it declined after 30 d and vanished after 60 and 90 d of tungstate administration, whereas a trend toward a reduction in basal hyperglycemia was observed on prolonged treatment. Oral tungstate was unable to modify glucose-stimulated insulin secretion in the isolated perfused pancreas, as well as muscle glycogen levels, hepatic glucose metabolism, and insulin-stimulated lipogenesis in isolated adipocytes. Nevertheless, the decreased insulin content of pancreatic islets of diabetic rats was partially restored on prolonged tungstate treatment. In conclusion, in the STZ-nicotinamide model of diabetes, tungstate was unable to permanently correct the alterations in glucose metabolism, despite some indirect evidence of a trophic effect on beta-cells. The ineffectiveness of tungstate could be related to the absence, in this diabetic syndrome, of relevant metabolic alterations in the liver, which thus appear to constitute the major target of tungstate action.

  7. Effectiveness of oral litholysis therapy for improving glucose intolerance and malnutrition in patients with poor results following endoscopic therapy and extracorporeal shock wave lithotripsy for calcified pancreatic stones.

    PubMed

    Ashizawa, Nobuo; Hamano, Koichi; Noda, Aiji

    2015-10-01

    We report a case of pancreatolithiasis in which glucose intolerance and malnutrition were significantly improved after starting oral litholysis therapy (OLT) with use of trimethadione. A 43-year-old female with multiple calcified stones in the main and peripheral pancreatic ducts had experienced recurrent and severe attacks of pain for 7 years (from 21 to28 years of age). Impaired glucose tolerance was first noted at the age of 32 years. We started OLT after interventional endoscopic therapy combined with extracorporeal shock wave lithotripsy failed because of kink and stenosis of the main pancreatic duct (MPD). Over the next 9 years, a significant decrease in total pancreatic calcified stone volume was shown by computer analysis of follow-up computed tomography images. Larger stones completely disappeared without attacks of pain. In addition, both glucose intolerance and insulin secretion were significantly ameliorated, followed by improvement of malnutrition. OLT may induce intraductal decompression by dissolving stones in the peripheral ducts as well as the MPD, with resulting preservation of endocrine function and improvement of malnutrition. Since the present results were obtained in a single case, further clinical trials are necessary to evaluate the value of performing OLT under various conditions to eliminate stones.

  8. Dietary intake of boiled breadfruit (Treculia africana) seeds did not improve hyperglycemia in streptozotocin induced diabetic rats: Effect on the oral glucose tolerance of normoglycemic rats.

    PubMed

    Eleazu, Chinedum; Ezekwibe, Ifeoma; Egbe, Mary; Saidu, Sanni; Eleazu, Kate; Egedigwe, Chima

    2017-01-01

    Although African breadfruit (Treculia africana) is said to be useful in the dietary management of diabetes, the effect of cooking on its glycemic index has not been reported. Hence this study has investi- gated the effect of a dietary intake of boiled breadfruit on the serum glucose, glucose tolerance, body weights and relative organ weights of streptozotocin (STZ) induced diabetic rats. Twenty albino rats were used and were divided into four groups of five rats. Groups 1 (normal control) and 2 (diabetic control) received standard rat pellets while groups 3 (diabetic-test group) and 4 (non-diabetic) rats received breadfruit. The blood glucose of the normoglycemic rats fed standard rat feeds peaked at 30 min (149.75 ±11.12 mg/dl) following oral glucose loading (3 g/kg) but reduced to 85.25 ±21.05 mg/dl after another 90 min, while the blood glucose of the normoglycemic rats fed breadfruit peaked at 30 min (146.25 ±15.22 mg/dl) follow- ing oral glucose loading, but elevated (130.75 ±36.69 mg/dl) after another 90 min. There was significant elevation (P < 0.05) of the serum glucose, relative liver weight (RLW) and relative kidney weight (RKW) but a significant decrease in the body weights of the diabetic control compared with the normal control; no sig- nificant difference (P > 0.05) in the serum glucose, body weights, RLW and RKW of the test group compared with the diabetic control, and no significant differences (P > 0.05) in the serum glucose, body weights, RLW and RKW of the normal rats fed the breadfruit diet compared to the normal control. The study showed that the traditional method of cooking African breadfruit negatively affects its hypoglycemic property.

  9. Increased hemoglobin A1c threshold for prediabetes remarkably improving the agreement between A1c and oral glucose tolerance test criteria in obese population.

    PubMed

    Li, Jie; Ma, Hao; Na, Lixin; Jiang, Shuo; Lv, Lin; Li, Gang; Zhang, Wei; Na, Guanqiong; Li, Ying; Sun, Changhao

    2015-05-01

    It is unclear why the prevalence of diabetes and prediabetes, especially prediabetes, between diagnosed by oral glucose tolerance test (OGTT) and hemoglobin A1c (HbA1c) criteria, is substantially discordant. We aimed to evaluate the effects of obesity on the agreement between HbA1c and OGTT for diagnosing diabetes and prediabetes and identify the optimal HbA1c cutoff values in different body mass index (BMI) classifications. In a population-based, cross-sectional study in Harbin, China, 4325 individuals aged 20-74 years without a prior diagnosed diabetes were involved in this study. measure The performance and optimal cutoff points of HbA1c were assessed by receiver-operating characteristic curve. The contribution of BMI to HbA1c was analyzed by structural equational model. The agreement between HbA1c criteria and OGTT decreased with BMI gain (κ = 0.359, 0.312, and 0.275 in a normal weight, overweight, and obese population, respectively). The structural equational model results showed that BMI was significantly associated with HbA1c in normal glucose tolerance and prediabetes subjects but not in diabetes subjects. At a specificity of 80% for prediabetes and 97.5% for diabetes, the optimal HbA1c cutoff points for prediabetes and diabetes were 5.6% and 6.4% in normal-weight, 5.7% and 6.5% in overweight, and 6.0% and 6.5% in an obese population. When the new HbA1c cutoff values were used, the agreement in obese subjects increased almost to the level in normal-weight subjects. The poor agreement between HbA1c and OGTT criteria in an obese population can be significantly improved through increasing the HbA1c threshold for prediabetes.

  10. Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.

    PubMed

    Kumakura, Atsushi; Shikuma, Junpei; Ogihara, Norikazu; Eiki, Jun-ichi; Kanazawa, Masao; Notoya, Yōko; Kikuchi, Masatoshi; Odawara, Masato

    2013-01-01

    The liver plays an important role in maintaining glucose homeostasis in the body. In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver. In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting. Thus, the liver contributes to maintaining blood glucose level within normoglycemic range. Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content. In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected. We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity. On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups. These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity. In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.

  11. Meal related glucose monitoring is a method of diagnosing glucose intolerance in pregnancies with high probability of gestational diabetes but normal glucose tolerance by oral glucose tolerance test.

    PubMed

    John, Mathew; Gopinath, Deepa

    2013-06-01

    Gestational diabetes mellitus diagnosed by classical oral glucose tolerance test can result in fetal complications like macrosomia and polyhydramnios. Guidelines exist on management of patients diagnose by abnormal oral glucose tolerance test with diet modification followed by insulin. Even patients with abnormal oral glucose tolerance test maintaining apparently normal blood sugars with diet are advised insulin if there is accelerated fetal growth. But patients with normal oral glucose tolerance test can present with macrosomia and polyhydramnios. These patients are labelled as not having gestational diabetes mellitus and are followed up with repeat oral glucose tolerance test. We hypothesise that these patients may have an altered placental threshold to glucose or abnormal sensitivity of fetal tissues to glucose. Meal related glucose monitoring in these patients can identify minor abnormalities in glucose disturbance and should be treated to targets similar to physiological levels of glucose in non pregnant adults.

  12. Metabolite Profiles During Oral Glucose Challenge

    PubMed Central

    Ho, Jennifer E.; Larson, Martin G.; Vasan, Ramachandran S.; Ghorbani, Anahita; Cheng, Susan; Rhee, Eugene P.; Florez, Jose C.; Clish, Clary B.; Gerszten, Robert E.; Wang, Thomas J.

    2013-01-01

    To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m2) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P ≤ 0.0005 for all). Amino acids, β-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in β-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state. PMID:23382451

  13. Evaluation of a Self-Administered Oral Glucose Tolerance Test

    PubMed Central

    Bethel, M. Angelyn; Price, Hermione C.; Sourij, Harald; White, Sarah; Coleman, Ruth L.; Ring, Arne; Kennedy, Irene E.C.; Tucker, Lynne; Holman, Rury R.

    2013-01-01

    OBJECTIVE To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes. PMID:23321216

  14. Evaluation of a self-administered oral glucose tolerance test.

    PubMed

    Bethel, M Angelyn; Price, Hermione C; Sourij, Harald; White, Sarah; Coleman, Ruth L; Ring, Arne; Kennedy, Irene E C; Tucker, Lynne; Holman, Rury R

    2013-06-01

    To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.

  15. An integrated glucose-insulin model to describe oral glucose tolerance test data in healthy volunteers.

    PubMed

    Silber, Hanna E; Frey, Nicolas; Karlsson, Mats O

    2010-03-01

    The extension of the previously developed integrated models for glucose and insulin (IGI) to include the oral glucose tolerance test (OGTT) in healthy volunteers could be valuable to better understand the differences between healthy individuals and those with type 2 diabetes mellitus (T2DM). Data from an OGTT in 23 healthy volunteers were used. Analysis was based on the previously developed intravenous model with extensions for glucose absorption and incretin effect on insulin secretion. The need for additional structural components was evaluated. The model was evaluated by simulation and a bootstrap. Multiple glucose and insulin concentration peaks were observed in most individuals as well as hypoglycemic episodes in the second half of the experiment. The OGTT data were successfully described by the extended basic model. An additional control mechanism of insulin on glucose production improved the description of the data. The model showed good predictive properties, and parameters were estimated with good precision. In conclusion, a previously presented integrated model has been extended to describe glucose and insulin concentrations in healthy volunteers following an OGTT. The characterization of the differences between the healthy and diabetic stages in the IGI model could potentially be used to extrapolate drug effect from healthy volunteers to T2DM.

  16. Improvement in glucose tolerance due to Momordica charantia (karela).

    PubMed

    Leatherdale, B A; Panesar, R K; Singh, G; Atkins, T W; Bailey, C J; Bignell, A H

    1981-06-06

    The effect of karela (Momordica charantia), a fruit indigenous to South America and Asia, on glucose and insulin concentrations was studied in nine non-insulin-dependent diabetics and six non-diabetic laboratory rats. A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats. Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance. Improvement in glucose tolerance was not associated with an increase in serum insulin responses. These results show that karela improves glucose tolerance in diabetes. Doctors supervising Asian diabetics should be aware of the fruit's hypoglycaemic properties.

  17. Improvement in glucose tolerance due to Momordica charantia (karela).

    PubMed Central

    Leatherdale, B A; Panesar, R K; Singh, G; Atkins, T W; Bailey, C J; Bignell, A H

    1981-01-01

    The effect of karela (Momordica charantia), a fruit indigenous to South America and Asia, on glucose and insulin concentrations was studied in nine non-insulin-dependent diabetics and six non-diabetic laboratory rats. A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats. Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance. Improvement in glucose tolerance was not associated with an increase in serum insulin responses. These results show that karela improves glucose tolerance in diabetes. Doctors supervising Asian diabetics should be aware of the fruit's hypoglycaemic properties. PMID:6786635

  18. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    PubMed

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 <11.1 mmol/L), and none with diabetes. Using the continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and <11.1 mmol/L (IGT) in 9 children (69%) and >11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of <2.7 mmol/L (hypoglycemia). No glycemic abnormality was detected using HbA1C (5.7 ± 0.3%). 11/13 patients had HOMA values >2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  19. Hepatic portal vein denervation impairs oral glucose tolerance but not exenatide's effect on glycemia.

    PubMed

    Ionut, Viorica; Castro, Ana Valeria B; Woolcott, Orison O; Stefanovski, Darko; Iyer, Malini S; Broussard, Josiane L; Burch, Miguel; Elazary, Ram; Kolka, Cathryn M; Mkrtchyan, Hasmik; Bediako, Isaac Asare; Bergman, Richard N

    2014-10-15

    The hepatoportal area is an important glucohomeostatic metabolic sensor, sensing hypoglycemia, hyperglycemia, and hormones such as glucagon-like peptide-1 (GLP-1). We have reported previously that activation of hepatoportal sensors by intraportal infusion of glucose and GLP-1 or by subcutaneous administration of GLP-1 receptor activator exenatide and of intraportal glucose improved glycemia independent of corresponding changes in pancreatic hormones. It is not clear whether this effect is mediated via the portal vein (PV) or by direct action on the liver itself. To test whether receptors in the PV mediate exenatide's beneficial effect on glucose tolerance, we performed 1) paired oral glucose tolerance tests (OGTT) with and without exenatide and 2) intravenous glucose tolerance tests before and after PV denervation in canines. Denervation of the portal vein affected oral glucose tolerance; post-denervation (POST-DEN) OGTT glucose and insulin AUC were 50% higher than before denervation (P = 0.01). However, portal denervation did not impair exenatide's effect to improve oral glucose tolerance (exenatide effect: 48 ± 12 mmol·l⁻¹·min before vs. 64 ± 26 mmol·l⁻¹·min after, P = 0.67). There were no changes in insulin sensitivity or secretion during IVGTTs. Portal vein sensing might play a role in controlling oral glucose tolerance during physiological conditions but not in pharmacological activation of GLP-1 receptors by exenatide.

  20. An integrated glucose-insulin model to describe oral glucose tolerance test data in type 2 diabetics.

    PubMed

    Jauslin, Petra M; Silber, Hanna E; Frey, Nicolas; Gieschke, Ronald; Simonsson, Ulrika S H; Jorga, Karin; Karlsson, Mats O

    2007-10-01

    An integrated model for the glucose-insulin system describing oral glucose tolerance test data was developed, extending on a previously introduced model for intravenous glucose provocations. Model extensions comprised the description of glucose absorption by a chain of transit compartments with a mean transit time of 35 minutes, a bioavailability of 80%, and a representation of the incretin effect, expressed as a direct effect of the glucose absorption rate on insulin secretion. The ability of the model to predict the incretin effect was assessed by simulating the observed difference in insulin response following an oral glucose tolerance test compared with an isoglycemic glucose infusion mimicking an oral glucose tolerance test profile. The extension of the integrated glucose-insulin model to gain information from oral glucose tolerance test data considerably expands its range of applications because the oral glucose tolerance test is one of the most common glucose challenge experiments for assessing the efficacy of hypoglycemic agents in clinical drug development.

  1. Effect of Different Periods of Fasting on Oral Glucose Tolerance

    PubMed Central

    Walsh, C. H.; O'Regan, J.; O'Sullivan, D. J

    1973-01-01

    The effect of different periods of fasting on oral glucose tolerance was investigated in 33 subjects. It was found that glucose tolerance deteriorated as the fasting period became shorter. This effect was seen almost exclusively in subjects over 40 years of age. Only the fasting blood sugar was affected by the duration of the pretest fast in younger subjects. PMID:4733248

  2. Oral nitrate therapy does not affect glucose metabolism in healthy men.

    PubMed

    Henstridge, Darren C; Duffy, Stephen J; Formosa, Melissa F; Ahimastos, Anna A; Thompson, Bruce R; Kingwell, Bronwyn A

    2009-11-01

    1. Previously, we demonstrated that nitric oxide (NO) may be an important mediator of peripheral glucose disposal. The aim of the present study was to determine whether acute oral nitrate therapy improves glucose metabolism in healthy individuals. 2. Healthy men (n = 10), aged between 19 and 46 years, participated in a randomized cross-over placebo-controlled study. During Visit 1, participants received a dose-graded intravenous infusion of sodium nitroprusside (SNP; titrated from a dose of 0.5 microg/kg per min to a maximum of 2 microg/kg per min and delivered at a rate of 2 mL/min over 30 min). On Visits 2, 3 and 4, participants received oral extended-release isosorbide mononitrate (120 mg), pentaerythritol tetranitrate (160 mg) and placebo in a randomized Latin square design (one treatment per visit). The main outcome measures were plasma glucose and insulin levels and glucose tolerance determined by an oral glucose tolerance test following the SNP infusion and 3 h after nitrate/placebo administration. Exhaled NO, cGMP and pulmonary blood flow were also measured for 3 h after administration of nitrate/placebo and after SNP infusion. 3. None of the nitrate interventions influenced measures of glucose metabolism. Following SNP infusion, there was no change in plasma glucose (P = 0.42) or insulin (P = 0.25) levels, and the response to a glucose load did not different from baseline (P = 0.46). Similarly, neither of the oral nitrates altered plasma glucose (P = 0.24) or insulin levels (P = 0.90) or glucose tolerance (P = 0.56) compared with placebo. 4. In conclusion, these results indicate that acute oral nitrate therapy does not influence glucose metabolism. Studies using NO donors in a chronic setting are required to clarify the role of NO in mediating peripheral glucose uptake.

  3. Evaluation of Oral Glucose Tolerance Test in Children With Epilepsy.

    PubMed

    Varlamis, Sotirios; Vavatsi, Norma; Pavlou, Evangelos; Kotsis, Vasileios; Spilioti, Martha; Kavga, Maria; Varlamis, George; Sotiriadou, Foteini; Agakidou, Eleni; Voutoufianakis, Spyridon; Evangeliou, Athanasios E

    2013-11-01

    Glucose metabolism of children with drug-resistant epilepsy, controlled by antiepileptic drugs epilepsy, and first-time nonfebrile seizures was studied through the performance of an oral glucose tolerance test and through insulin, C-peptide, and glycosylated hemoglobin measurements. In the refractory epilepsy group, there were more abnormal oral glucose tolerance test results (62.07%) in comparison to the controlled epilepsy group (25%) and the group of first-time seizures (21.21%). There was a significant difference between the group of refractory epilepsy and every other group concerning the abnormality of the oral glucose tolerance test (P < .05). The mean values of insulin, HbA1c, and C-peptide levels were normal for all groups. The results of the present study suggest that there is a distinction of refractory epilepsies from the drug-controlled ones and the first-induced seizures relating to their metabolic profile, regardless of the type of seizures.

  4. Effects of oral glucose on systemic glucose metabolism during hyperinsulinemic hypoglycemia in normal man.

    PubMed

    Poulsen, P L; Orskov, L; Grøfte, T; Møller, J; Holst, J J; Schmitz, O; Møller, N

    2000-12-01

    The widespread use of oral glucose in the treatment of hypoglycemia is mainly empirically based, and little is known about the time lag and subsequent magnitude of effects following its administration. To define the systemic impact and time course of effects following oral glucose during hypoglycemia, we investigated 7 healthy young men twice. On both occasions, a 6-hour hyperinsulinemic (1.5 mU/kg/min)-hypoglycemic clamp was performed to ensure similar plasma glucose profiles during a stepwise decrease toward a nadir less than 50 mg/100 mL after 3 hours. On the first occasion, subjects ingested 40 g glucose and 4 g 3-ortho-methylglucose ([3-OMG] to trace glucose absorption) dissolved in 400 mL tap water after 3.5 hours. The second examination was identical except for the omission of 40 g oral glucose, and glucose levels were clamped at hypoglycemic concentrations similar to those recorded on the first examination. Plasma glucose curves were superimposable, and all participants reached a nadir less than 50 mg/100 mL. Similar increases in growth hormone (GH) and glucagon were observed in both situations. The glucose infusion rates (GIRs) were lower after oral glucose, with the difference starting after 5 to 10 minutes, being statistically significant after 20 minutes, and reaching a maximum of 8.5 +/- 1.6 mg/kg/min after 40 minutes. Circulating 3-OMG increased after 20 minutes. In both situations, infusion of insulin resulted in insulin levels of approximately 150 microU/mL and a suppression of C-peptide levels from 2.0 to 1.1 nmol/L (P < .01). After glucose ingestion, both serum C-peptide and glucagon-like peptide-1 (GLP-1) increased (C-peptide from 1.1 +/- 0.05 to 1.4 +/- 0.05 nmol/L and GLP-1 from 3.2 +/- 0.8 to 18.1 +/- 3.3 pmol/L), in contrast to the situation without oral glucose (P < .05). Isotopically determined glucose turnover was similar. In conclusion, our data suggest that oral glucose affects systemic glucose metabolism rapidly after 5 to 10 minutes

  5. Oral 30% glucose provides sufficient sedation in newborns during MRI.

    PubMed

    Eker, H Evren; Cok, Oya Yalcin; Çetinkaya, Bilin; Aribogan, Anis

    2017-04-01

    Newborns are often sedated during MRI but sedation itself creates adverse events and management is more challenging in this environment. Oral glucose/sucrose administration has been studied in newborns during painful procedures; however, its effectiveness in keeping newborns sleepy and motionlessness during painless procedures has not been demonstrated. The objective of this study was to describe effectiveness of oral 30% glucose administration by comparing with intravenous midazolam sedation for newborns during MRI. One hundred twelve ASA II-III newborns who required care in the ICU and were scheduled for MRI with sedation were included. Group I received 30% glucose solution orally with 0.5-1 ml increments up to 2 ml/3 kg doses and group II received intravenous 0.1 mg/kg midazolam with 0.05 mg/kg repetition. The procedure was considered satisfactory when MRI images were not disturbed by patient movement after oral glucose or intravenous midazolam administration. The efficiency of the techniques, additional dose and rescue sedation requirements, blood glucose levels following oral 30% glucose suckling and presence of adverse events were recorded. Demographic data was similar between groups. The efficiency of the procedures were similar between groups (78.9%, in group I and 66.1%, in group II). The blood glucose levels were within normal range in group I whereas transient desaturation and apnea occurred in 8 neonates in group II (p = 0.006). Oral 30% glucose administration for newborns during MRI is as effective as standard sedation protocol with midazolam. Thereby, we recommend and support the integration of this safe and reliable technique into routine practice for newborns during MRI.

  6. 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.

  7. Orally administered glucagon-like peptide-1 affects glucose homeostasis following an oral glucose tolerance test in healthy male subjects.

    PubMed

    Steinert, R E; Poller, B; Castelli, M C; Friedman, K; Huber, A R; Drewe, J; Beglinger, C

    2009-12-01

    Glucagon-like peptide-1 (GLP-1) exerts several effects on glucose homeostasis and reduces food intake. After its release from intestinal L cells, GLP-1 is subject to (i) rapid breakdown by dipeptidyl peptidase IV and (ii) high liver extraction. The highest concentrations of GLP-1 are found in the splanchnic blood rather than in the systemic circulation. An oral delivery system would mimic endogenous secretion. Here we investigated the pharmacokinetic/pharmacodynamic (PK/PD) effects of a single dose (2 mg) of oral GLP-1 administered prior to an oral glucose tolerance test (OGTT) in 16 healthy males. GLP-1 was rapidly absorbed from the gut, leading to tenfold higher plasma concentrations compared with controls. The PD profile was consistent with reported pharmacology; GLP-1 significantly stimulated basal insulin release (P < 0.027), with marked effects on glucose levels. The postprandial glucose peak was delayed with GLP-1, suggesting an effect on gastric emptying.

  8. Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk.

    PubMed

    Hulman, Adam; Simmons, Rebecca K; Vistisen, Dorte; Tabák, Adam G; Dekker, Jacqueline M; Alssema, Marjan; Rutters, Femke; Koopman, Anitra D M; Solomon, Thomas P J; Kirwan, John P; Hansen, Torben; Jonsson, Anna; Gjesing, Anette Prior; Eiberg, Hans; Astrup, Arne; Pedersen, Oluf; Sørensen, Thorkild I A; Witte, Daniel R; Færch, Kristine

    2017-02-01

    We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak times varied greatly between groups, ranging from 7-12 mmol/L, and 35-70 min. The group with the lowest and earliest plasma glucose peak had the lowest estimated cardiovascular risk, while the group with the most delayed plasma glucose peak and the highest 2-h value had the highest estimated risk. One group, with normal fasting and 2-h values, exhibited an unusual profile, with the highest glucose peak and the highest proportion of smokers and men. The heterogeneity in glucose response curves and the distinct cardiometabolic risk profiles may reflect different underlying physiologies. Our results warrant more detailed studies to identify the source of the heterogeneity across the different phenotypes and whether these differences play a role in the development of type 2 diabetes and cardiovascular disease.

  9. Correspondence of continuous interstitial glucose measurement against arterialised and capillary glucose following an oral glucose tolerance test in healthy volunteers.

    PubMed

    Dye, Louise; Mansfield, Michael; Lasikiewicz, Nicola; Mahawish, Lena; Schnell, Rainer; Talbot, Duncan; Chauhan, Hitesh; Croden, Fiona; Lawton, Clare

    2010-01-01

    The aim of the present study was to validate the Glucoday continuous interstitial ambulatory glucose-monitoring device (AGD) against plasma glucose measured from arterialised venous (AV) and glucose from capillary whole blood (finger prick, FP) in non-diabetic subjects in response to an oral glucose tolerance test. Fifteen healthy overweight men (age 30-49 years, BMI 26-31 kg/m2) participated. Glucose levels were measured before, during and after consumption of an oral 75 g glucose load using twelve FP samples and forty-four 1 ml AV blood samples during 180 min. Interstitial glucose was measured via the AGD. Three venous samples for fasting insulin were taken to estimate insulin resistance. Profiles of AGD, AV and FP glucose were generated for each participant. Glucose values for each minute of the measurement period were interpolated using a locally weighted scatterplot smoother. Data were compared using Bland-Altman plots that showed good correspondence between all pairs of measurements. Concordance between the three methods was 0.8771 (Kendall's W, n 15, P < 0.001). Concordance was greater between AV and FP (W = 0.9696) than AGD and AV (W = 0.8770) or AGD and FP (W = 0.8764). Analysis of time to peak glucose indicated that AGD measures lagged approximately 15 min behind FP and AV measures. Percent body fat was significantly correlated with time to peak glucose levels for each measure, while BMI and estimated insulin resistance (homeostatic model assessment, HOMA) were not. In conclusion, AGD shows good correspondence with FP and AV glucose measures in response to a glucose load with a 15 min time lag. Taking this into account, AGD has potential application in nutrition and behaviour studies.

  10. New insulin sensitivity index from the oral glucose tolerance test.

    PubMed

    Kazama, Youichiro; Takamura, Toshinari; Sakurai, Masaru; Shindo, Hisakazu; Ohkubo, Eizho; Aida, Kaoru; Harii, Norikazu; Taki, Katsumi; Kaneshige, Masahiro; Tanaka, Shoichiro; Shimura, Hiroki; Endo, Toyoshi; Kobayashi, Tetsuro

    2008-01-01

    A new insulin sensitivity index was devised on the basis of an autoregressive model and its validity was investigated. Using data from the 75-g oral glucose tolerance test (OGTT), 115 subjects were divided into 3 groups: 40 with normal glucose tolerance, 34 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus. The new insulin sensitivity index: oral glucose insulin sensitivity index (GSI) was calculated from five sets of plasma glucose and insulin levels obtained at 0, 30, 60, 90 and 120 min during OGTT using a formula based on an autoregressive model. Forty-three of the 115 subjects were examined for insulin sensitivity index (ISI) by euglycemic hyperinsulinemic clamp. GSI decreased in the order of normal glucose tolerance group>impaired glucose tolerance group>diabetic group. There was a significant correlation between GSI and the ISI derived from euglycemic hyperinsulinemic clamp study data in all 43 subjects who underwent both tests (r=0.72; P<0.0001). The ISI calculated by previous methods poorly correlated with the ISIs obtained by euglycemic hyperinsulinemic clamp study. In conclusion, this new insulin sensitivity index based on the data obtained from OGTT using an autoregressive model is comparable to an insulin sensitivity index by euglycemic hyperinsulinemic clamp technique and may be superior to previous indexes that have been devised to determine insulin sensitivity from OGTT data.

  11. Editorial: Oral glucose/electrolyte therapy for acute diarrhoea.

    PubMed

    1975-01-11

    Much clinical experience has been gained in the use of the glucose/electrolyte oral solutions in the treatment of acute diarrhea. Those patients who are in shock or too weak to drink need intravenous fluids to correct their total deficit. With isotonic polyelectrolyte fluids rehydration may be achieved in 2-4 hours. Subsequently, most of these patients can be given oral fluids to replace continuing stool loss. Patients who are not in shock and who are sufficiently strong to drink at the outset nearly always can be rehydrated with oral fluids alone. Vomiting is most likely caused by acidosis and volume depletion, and these can be corrected in severely dehydrated patients by intravenous therapy and by oral therapy in those not in shock and able to drink by oral therapy. Proponents of oral glucose/electrolyte therapy for diarrhea, like other proponents of new treatments, have great visions of its benefits to the world, yet these visions require validation. The biggest problem will be getting glucose and electrolytes to where they are most needed -- at the level of home and village.

  12. Prediabetes Phenotype Influences Improvements in Glucose Homeostasis with Resistance Training

    PubMed Central

    Eikenberg, Joshua D.; Savla, Jyoti; Marinik, Elaina L.; Davy, Kevin P.; Pownall, John; Baugh, Mary E.; Flack, Kyle D.; Boshra, Soheir; Winett, Richard A.; Davy, Brenda M.

    2016-01-01

    Purpose To determine if prediabetes phenotype influences improvements in glucose homeostasis with resistance training (RT). Methods Older, overweight individuals with prediabetes (n = 159; aged 60±5 yrs; BMI 33±4 kg/m2) completed a supervised RT program twice per week for 12 weeks. Body weight and composition, strength, fasting plasma glucose, 2-hr oral glucose tolerance, and Matsuda-Defronza estimated insulin sensitivity index (ISI) were assessed before and after the intervention. Participants were categorized according to their baseline prediabetes phenotype as impaired fasting glucose only (IFG) (n = 73), impaired glucose tolerance only (IGT) (n = 21), or combined IFG and IGT (IFG/IGT) (n = 65). Results Chest press and leg press strength increased 27% and 18%, respectively, following the 12-week RT program (both p<0.05). Waist circumference (-1.0%; pre 109.3±10.3 cm, post 108.2±10.6 cm) and body fat (-0.6%; pre 43.7±6.8%, post 43.1±6.8%) declined, and lean body mass (+1.3%; pre 52.0±10.4 kg, post 52.7±10.7 kg) increased following the intervention. Fasting glucose concentrations did not change (p>0.05) following the intervention. However, 2-hr oral glucose tolerance improved in those with IGT (pre 8.94±0.72 mmol/l, post 7.83±1.11 mmol/l, p<0.05) and IFG/IGT (pre 9.66±1.11mmol/l, post 8.60±2.00 mmol/l) but not in those with IFG (pre 6.27±1.28mmol/l, post 6.33± 1.55 mmol/l). There were no significant changes in ISI or glucose area under the curve following the RT program. Conclusions RT without dietary intervention improves 2-hr oral glucose tolerance in individuals with prediabetes. However, the improvements in glucose homeostasis with RT appear limited to those with IGT or combined IFG and IGT. Trial Registration ClinicalTrials.gov: NCT01112709 PMID:26840904

  13. Calcium homeostasis during oral glucose load in healthy women.

    PubMed

    D'Erasmo, E; Pisani, D; Ragno, A; Raejntroph, N; Vecci, E; Acca, M

    1999-04-01

    It has been demonstrated that in healthy subjects during oral glucose tolerance test, serum calcium declines, while urinary calcium excretion increases, even if there is not a general agreement in this regard. The study was carried out in order to evaluate the effects of glucose oral load on calcium homeostasis in eight healthy adult women, also considering ionized calcium, plasma insulin and parathyroid hormone changes. The results showed a decline of total and ionized serum calcium (p < 0.05 and p < 0.01, respectively; maximum of the decrease at time 120'), in parallel with the increase of urinary calcium/ creatinine ratio (p < 0.05). Serum glucose and insulin increase (p < 0.0001 and p < 0.0005 respectively; maximum value at time 60'), while the parathyroid hormone level decreases (maximum decline at time 120', p < 0.01). No changes were observed in fasting control subjects for all parameters considered. The changes of these parameters with time suggest that the effects of glucose oral load on calcium metabolism in healthy adult women may be the consequence of parathyroid hormone suppression induced by acute hyperglycemia/hyperinsulinemia. The results confirm in vivo the PTH behaviour in vitro, on cultured bovine parathyroid cells, with high glucose concentration.

  14. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults.

    PubMed

    Moore, M C; Cherrington, A D; Mann, S L; Davis, S N

    2000-12-01

    In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: < 0.05). Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTT. In conclusion, low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.

  15. Preparation of patients submitted to thyroidectomy with oral glucose solutions.

    PubMed

    Libiszewski, Michał; Drozda, Rafał; Smigielski, Janusz; Kuzdak, Krzysztof; Kołomecki, Krzysztof

    2012-05-01

    The AIM OF THE STUDY was to determine postoperative insulin-resistance in patients subject to total thyroidectomy, the prevalence of subjective feelings of hunger immediately before surgery, and the incidence of nausea/vomiting after surgery in patients prepared for elective operations by means of oral glucose solutions. The study group comprised 115 patients, including 71 patients prepared for surgery by means of oral glucose solutions (12.5% glucose) administered 12 and 3 hours before the procedure, at a dose of 800 and 400 ml. The control group comprised 44 patients prepared for surgery by means of the traditional manner- the last meal was served before 2pm the day before the surgical procedure, while fluids before 10pm. Considering both groups, we evaluated glucose and insulin levels three times, as well as determined the insulin-resistance ratio (HOMA-IR) 24 before, and 12 hours and 7 days after surgery. The incidence of nausea and vomiting after surgery, and the subjective feeling of hunger before surgery were also evaluated. Statistically significant differences considering insulin level and HOMA-IR values were observed during the II and III measurements. The glucose and insulin values, and the HOMA-IR insulin-resistance ratio, showed no statistically significant differences during measurement I. No statistically significant glucose level differences were observed during measurements II and III. A significantly greater subjective feeling of hunger before surgery and nausea/vomiting afterwards were observed in the control group. The preparation of patients with oral glucose solutions decreases the incidence of postoperative (thyroidectomy) insulin-resistance, and occurrence of nausea/vomiting during the postoperative period.

  16. Yam contributes to improvement of glucose metabolism in rats.

    PubMed

    Hashimoto, Naoto; Noda, Takahiro; Kim, Sun-Ju; Sarker, Md Zaidul Islam; Yamauchi, Hiroaki; Takigawa, Shigenobu; Matsuura-Endo, Chie; Suzuki, Tatsuro; Han, Kyu-Ho; Fukushima, Michihiro

    2009-09-01

    To investigate whether yam improves glucose metabolism, yam-containing diets were given to Wistar rats. In a short-term experiment, fasted-rats were given 1.0 g of a control and 20% yam-containing diets. At 60 min after start of the feeding, glucose level in the yam diet group was lower or tended to be lower than that in the control diet. Insulin levels at 30 min and 60 min were significantly lower than those in the control group. In a long-term experiment, a normal diet (N) or 25% high fat diets with (Y) or without 15% yam powder (HF) were given to rats for 4 weeks. At 4 weeks, in an oral glucose tolerance test, the area under the curve (AUC) of plasma glucose level was higher in the HF group than that in the N group, whereas those in the Y groups did not differ from that in the N group. Glycosylated hemoglobin levels had similar tendency to the AUCs. Plasma leptin levels in the Y groups were significantly higher than that in the N group. In conclusion, yam may contribute to improvement of glucose metabolism. Additionally, we speculated that leptin level is possibly involved in the insulin-response to yam diets.

  17. Effect of oral glucose on serum zinc in the elderly

    SciTech Connect

    Lopez, A.L.; Kohrs, M.B.; Horwitz, D.L.; Cyborski, C.K.; Czajka-Narins, D.M.; Kamath, S.

    1986-03-05

    To determine the effect of glucose loading on serum zinc concentrations, 34 elderly subjects aged 60-86 y were studied. Anthropometric data, medical and dietary histories were obtained. Serum zinc and glucose concentrations were obtained fasting and 1/2, 1, 1 1/2, 2 and 3 h after 75 g oral glucose load; glycohemoglobin and fasting serum lipids were also determined. For comparison, the subjects were categorized as: normal or low serum zinc concentrations; normal or high body mass index BMI; normal or high sum of skinfolds and normal or high serum cholesterol. Results showed that low serum zinc concentrations increased significantly over baseline values after the glucose load and did not return to fasting levels. On the other hand, mean serum zinc concentrations significantly declined without recovery for those with normal zinc values. For the total group, no significant differences were noted between fasting values and subsequent time periods. No correlations were noted between fasting serum zinc and area under the curve for zinc except in the high BMI group (positive correlation observed). For the high BMI group, fasting serum zinc differed significantly from the succeeding measurements except for 30 min. For the group as a whole, mean serum zinc concentration was within normal limits (76.9 +/- 2.8 mcg/ml): mean zinc intake was less than 2/3rds the RDA. They conclude that glucose ingestion may alter serum zinc and should be considered in interpreting these levels.

  18. Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.

    PubMed

    Vazquez-Anaya, Guillermo; Martinez, Bridget; Soñanez-Organis, José G; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

    2017-03-01

    Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T4) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T4 (8.0 µg/100 g BM/day × 5 weeks). T4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T4-treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T4 treatment increased the influx of T4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis.

  19. [Flat curves of oral glucose tolerance tests (author's transl)].

    PubMed

    Slama, G; Tchobroutsky, G

    1980-04-26

    Patients are often referred to diabetologists on account of a flat curve of oral glucose tolerance test. This abnormality, however, is virtually never associated with a serious metabolic disorder and in any case, it never points to a disease that cannot be diagnosed by questioning or by straightforward clinical examination, nor confirmed by a more specific laboratory test. The curve may be flat for technical reasons (e.g. rejection of the glucose administered, timing of blood withdrawals and assays), for physiological reasons (differences between venous and arteriolo-capillary blood), or for pathological reasons (interaction with drugs, pituitary, thyroid or adrenal insufficiency, digestive malabsorption) but it never implies organic hypoglycaemia nor diabetes mellitus.

  20. Improved Algorithm for Automated Glucose Clamps.

    PubMed

    Kuhlenkötter, Mareike; Heise, Tim; Benesch, Carsten

    2017-02-01

    In glucose clamp experiments, blood glucose concentrations (BGs) are kept as close as possible to a predefined target level using variable glucose infusion rates (GIRs). In automated clamps, GIRs are calculated by algorithms implemented in the device (e.g., the Biostator). Low BG- and GIR-variability is needed for high clamp quality. We therefore tried to reduce oscillations in both BG and GIR with an improved algorithm implemented in ClampArt, a modern clamp device. The Biostator algorithm was first improved by numerical simulations of glucose clamps (in silico). With the results of the simulations, we started in vitro experiments using the ClampArt device and a container with water and glucose as "test subject." After a small pilot in vivo study, a larger clinical study was performed to compare the original with the optimized algorithm. With the improved algorithm, in silico, in vitro, and in vivo experiments showed reduced oscillations in both BG and GIR. In the clinical study, the coefficient of variation (CV) of BG values was lowered from 6.0% (4.6%-7.8%) [median (interquartile range)] to 4.2% (3.6%-5.0%), P < 0.0001 and the CV of GIR from 60.7% (49.6%-82.0%) to 43.5% (32.8%-57.2%), P < 0.0001. Other clamp quality parameters did not change substantially, median deviation from target slightly increased from 0.6% (0.2%-1.0%) to 1.1% (0.7%-1.5%), P = 0.0005, whereas utility did not change [97.0% (93.4%-100.0%) vs. 97.0% (94.0%-98.8%), P = 0.57]. With the improved algorithm, all experiments confirmed a reduction in BG- and GIR-oscillations without a major impact on other glucose clamp parameters. The optimized algorithm has been implemented in ClampArt for all future glucose clamp studies.

  1. Perinatal exercise improves glucose homeostasis in adult offspring

    PubMed Central

    Carter, Lindsay G.; Lewis, Kaitlyn N.; Wilkerson, Donald C.; Tobia, Christine M.; Ngo Tenlep, Sara Y.; Shridas, Preetha; Garcia-Cazarin, Mary L.; Wolff, Gretchen; Andrade, Francisco H.; Charnigo, Richard J.; Esser, Karyn A.; Egan, Josephine M.; de Cabo, Rafael

    2012-01-01

    Emerging research has shown that subtle factors during pregnancy and gestation can influence long-term health in offspring. In an attempt to be proactive, we set out to explore whether a nonpharmacological intervention, perinatal exercise, might improve offspring health. Female mice were separated into sedentary or exercise cohorts, with the exercise cohort having voluntary access to a running wheel prior to mating and during pregnancy and nursing. Offspring were weaned, and analyses were performed on the mature offspring that did not have access to running wheels during any portion of their lives. Perinatal exercise caused improved glucose disposal following an oral glucose challenge in both female and male adult offspring (P < 0.05 for both). Blood glucose concentrations were reduced to lower values in response to an intraperitoneal insulin tolerance test for both female and male adult offspring of parents with access to running wheels (P < 0.05 and P < 0.01, respectively). Male offspring from exercised dams showed increased percent lean mass and decreased fat mass percent compared with male offspring from sedentary dams (P < 0.01 for both), but these parameters were unchanged in female offspring. These data suggest that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring. PMID:22932781

  2. Perinatal exercise improves glucose homeostasis in adult offspring.

    PubMed

    Carter, Lindsay G; Lewis, Kaitlyn N; Wilkerson, Donald C; Tobia, Christine M; Ngo Tenlep, Sara Y; Shridas, Preetha; Garcia-Cazarin, Mary L; Wolff, Gretchen; Andrade, Francisco H; Charnigo, Richard J; Esser, Karyn A; Egan, Josephine M; de Cabo, Rafael; Pearson, Kevin J

    2012-10-15

    Emerging research has shown that subtle factors during pregnancy and gestation can influence long-term health in offspring. In an attempt to be proactive, we set out to explore whether a nonpharmacological intervention, perinatal exercise, might improve offspring health. Female mice were separated into sedentary or exercise cohorts, with the exercise cohort having voluntary access to a running wheel prior to mating and during pregnancy and nursing. Offspring were weaned, and analyses were performed on the mature offspring that did not have access to running wheels during any portion of their lives. Perinatal exercise caused improved glucose disposal following an oral glucose challenge in both female and male adult offspring (P < 0.05 for both). Blood glucose concentrations were reduced to lower values in response to an intraperitoneal insulin tolerance test for both female and male adult offspring of parents with access to running wheels (P < 0.05 and P < 0.01, respectively). Male offspring from exercised dams showed increased percent lean mass and decreased fat mass percent compared with male offspring from sedentary dams (P < 0.01 for both), but these parameters were unchanged in female offspring. These data suggest that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring.

  3. Improvements in glucose tolerance with Bikram Yoga in older obese adults: a pilot study.

    PubMed

    Hunter, Stacy D; Dhindsa, Mandeep; Cunningham, Emily; Tarumi, Takashi; Alkatan, Mohammed; Tanaka, Hirofumi

    2013-10-01

    Bikram yoga is an exotic form of physical activity combining hatha yoga and thermal therapy that could positively impact metabolic health. Although this increasingly popular alternative exercise may be ideal for obese adults due to its low impact nature, few studies have elucidated the health benefits associated with it. As an initial step, we determined the effect of Bikram yoga on glucose tolerance. Fourteen young lean and 15 older obese subjects completed an 8-week Bikram yoga intervention in which classes were completed 3 times per week. Glucose tolerance was assessed using a 75 g oral glucose tolerance test. The area under the glucose curve following the oral glucose tolerance test was significantly reduced as a result of the Bikram Yoga intervention in older obese (P < 0.05) but not in young lean subjects. We concluded that a short-term Bikram yoga intervention improved glucose tolerance in older obese, but not in young lean adults.

  4. Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men.

    PubMed

    Klement, Johanna; Ott, Volker; Rapp, Kristina; Brede, Swantje; Piccinini, Francesca; Cobelli, Claudio; Lehnert, Hendrik; Hallschmid, Manfred

    2017-02-01

    In addition to its pivotal role in psychosocial behavior, the hypothalamic neuropeptide oxytocin contributes to metabolic control by suppressing eating behavior. Its involvement in glucose homeostasis is less clear, although pilot experiments suggest that oxytocin improves glucose homeostasis. We assessed the effect of intranasal oxytocin (24 IU) administered to 29 healthy, fasted male subjects on glucose homeostasis measured by means of an oral glucose tolerance test. Parameters of glucose metabolism were analyzed according to the oral minimal model. Oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to the glucose challenge, while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin compared with placebo induced a pronounced increase in β-cell responsivity (PHItotal) that was largely due to an enhanced dynamic response (PHId), and a more than twofold improvement in glucose tolerance (disposition index). Adrenocorticotropic hormone (ACTH), cortisol, glucagon, and nonesterified fatty acid (NEFA) concentrations were not or were only marginally affected. These results indicate that oxytocin plays a significant role in the acute regulation of glucose metabolism in healthy humans and render the oxytocin system a potential target of antidiabetic treatment. © 2017 by the American Diabetes Association.

  5. Improving oral health: current considerations.

    PubMed

    Ciancio, S

    2003-01-01

    The high incidence of periodontal disease among adults in the Western world indicates that in most cases, routine dental care could be considerably improved. The progressive effect of the disease suggests that improvements in oral cleanliness are mandatory if large numbers of adults are to retain their teeth into old age. Data show that periodontal disease can be minimized through effective plaque control, and that a combination of brushing, interdental cleaning, and chemotherapeutic agents (e.g. mouthwash) is beneficial to patients with plaque control problems. The vast majority of adults do not follow an adequate home-care routine. Average brushing times are low, and only a minority of patients regularly floss. In addition, in those patients who do regularly brush and floss, a deterioration of plaque control occurs over time, suggesting that compliance is a major issue. The principal challenge for dental professionals is to identify how best to elicit an improvement.

  6. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

    PubMed Central

    Saxena, Richa; Hivert, Marie-France; Langenberg, Claudia; Tanaka, Toshiko; Pankow, James S; Vollenweider, Peter; Lyssenko, Valeriya; Bouatia-Naji, Nabila; Dupuis, Josée; Jackson, Anne U; Kao, W H Linda; Li, Man; Glazer, Nicole L; Manning, Alisa K; Luan, Jian’an; Stringham, Heather M; Prokopenko, Inga; Johnson, Toby; Grarup, Niels; Boesgaard, Trine W; Lecoeur, Cécile; Shrader, Peter; O’Connell, Jeffrey; Ingelsson, Erik; Couper, David J; Rice, Kenneth; Song, Kijoung; Andreasen, Camilla H; Dina, Christian; Köttgen, Anna; Le Bacquer, Olivier; Pattou, François; Taneera, Jalal; Steinthorsdottir, Valgerdur; Rybin, Denis; Ardlie, Kristin; Sampson, Michael; Qi, Lu; van Hoek, Mandy; Weedon, Michael N; Aulchenko, Yurii S; Voight, Benjamin F; Grallert, Harald; Balkau, Beverley; Bergman, Richard N; Bielinski, Suzette J; Bonnefond, Amelie; Bonnycastle, Lori L; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Buchanan, Thomas A; Bumpstead, Suzannah J; Cavalcanti-Proença, Christine; Charpentier, Guillaume; Chen, Yii-Der Ida; Chines, Peter S; Collins, Francis S; Cornelis, Marilyn; Crawford, Gabriel J; Delplanque, Jerome; Doney, Alex; Egan, Josephine M; Erdos, Michael R; Firmann, Mathieu; Forouhi, Nita G; Fox, Caroline S; Goodarzi, Mark O; Graessler, Jürgen; Hingorani, Aroon; Isomaa, Bo; Jørgensen, Torben; Kivimaki, Mika; Kovacs, Peter; Krohn, Knut; Kumari, Meena; Lauritzen, Torsten; Lévy-Marchal, Claire; Mayor, Vladimir; McAteer, Jarred B; Meyre, David; Mitchell, Braxton D; Mohlke, Karen L; Morken, Mario A; Narisu, Narisu; Palmer, Colin N A; Pakyz, Ruth; Pascoe, Laura; Payne, Felicity; Pearson, Daniel; Rathmann, Wolfgang; Sandbaek, Annelli; Sayer, Avan Aihie; Scott, Laura J; Sharp, Stephen J; Sijbrands, Eric; Singleton, Andrew; Siscovick, David S; Smith, Nicholas L; Sparsø, Thomas; Swift, Amy J; Syddall, Holly; Thorleifsson, Gudmar; Tönjes, Anke; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Valle, Timo T; Waeber, Gérard; Walley, Andrew; Waterworth, Dawn M; Zeggini, Eleftheria; Zhao, Jing Hua; Illig, Thomas; Wichmann, H Erich; Wilson, James F; van Duijn, Cornelia; Hu, Frank B; Morris, Andrew D; Frayling, Timothy M; Hattersley, Andrew T; Thorsteinsdottir, Unnur; Stefansson, Kari; Nilsson, Peter; Syvänen, Ann-Christine; Shuldiner, Alan R; Walker, Mark; Bornstein, Stefan R; Schwarz, Peter; Williams, Gordon H; Nathan, David M; Kuusisto, Johanna; Laakso, Markku; Cooper, Cyrus; Marmot, Michael; Ferrucci, Luigi; Mooser, Vincent; Stumvoll, Michael; Loos, Ruth J F; Altshuler, David; Psaty, Bruce M; Rotter, Jerome I; Boerwinkle, Eric; Hansen, Torben; Pedersen, Oluf; Florez, Jose C; McCarthy, Mark I; Boehnke, Michael; Barroso, Inês; Sladek, Robert; Froguel, Philippe; Meigs, James B; Groop, Leif; Wareham, Nicholas J; Watanabe, Richard M

    2010-01-01

    Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18). PMID:20081857

  7. An elevated 1-h post- load glucose level during the oral glucose tolerance test detects prediabetes.

    PubMed

    Buysschaert, Martin; Bergman, Michael; Yanogo, Donald; Jagannathan, Ram; Buysschaert, Benoit; Preumont, Vanessa

    The objective of the study was to compare the diagnosis of dysglycemic states by conventional oral glucose tolerance test (OGTT) criteria (fasting and 2-h plasma glucose) with the 1-h post-load plasma glucose level. 34 individuals (mean age: 55±13years; BMI: 27.7±6.3kg/m(2)) at risk for prediabetes were administered a 75g OGTT. Individuals with normal glucose tolerance (NGT) or prediabetes were identified according to fasting and/or 2-h plasma glucose (PG) concentrations. Subsequently, subjects were divided in 2 groups: group 1 (n=21) with a 1-h PG<155mg/dl and group 2 (n=13) with a 1-h PG≥155mg/dl. HOMA was performed to assess β-cell function and insulin sensitivity. NGT or prediabetes based on conventional criteria correlated with the 1-h PGglucose value ≥155mg/dl is strongly associated with conventional criteria for (pre)diabetes and alterations of β-cell function. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  8. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    PubMed

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury.

  9. Oral glucose tolerance and hormonal response in heroin-dependent males.

    PubMed

    Reed, J L; Ghodse, A H

    1973-06-09

    Tests on 12 heroin addicts showed that their response to a glucose load differed from that in normal controls. Though the fasting blood sugar was normal, the rise in blood glucose after a standard 50-g oral glucose tolerance test was delayed and the rise smaller than in the controls. The heroin addicts had high resting insulin levels and a delayed peak response to an oral glucose load, and their growth hormone response was also abnormal.

  10. Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats

    PubMed Central

    Marchionne, Elizabeth M.; Diamond-Stanic, Maggie K.; Prasonnarong, Mujalin

    2012-01-01

    We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker (fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser473 phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy

  11. Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats.

    PubMed

    Marchionne, Elizabeth M; Diamond-Stanic, Maggie K; Prasonnarong, Mujalin; Henriksen, Erik J

    2012-01-01

    We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker (fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser(473) phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the

  12. Acute and Chronic Kudzu Improves Plasma Glucose Tolerance in Non-Diabetic CD-1 Mice.

    PubMed

    Carlson, Scott; Prasain, Jeevan K; Peng, Ning; Dai, Yanying; Wyss, J Michael

    2014-01-01

    Previous studies demonstrate that kudzu root extract and its major isoflavone (puerarin) improve glucose metabolism in animal models of insulin resistance and type 2 diabetes; however, these beneficial effects have not been investigated in normal glycemic mice. The present study investigates the effect of acute and chronic kudzu root extract supplementation on glucose tolerance in normoglycemic CD-1 mice. Male, adult CD-1 mice were fed a phytoestrogen-free diet containing 0.2% or 0.0% kudzu root extract for 6 weeks. Thereafter, they were acutely administered kudzu root extract (75 mg/kg BW; oral) or vehicle followed by a glucose challenge (2 g/kg BW; oral). In control fed mice, the acute glucose challenge increased blood glucose ~300% after 30 minutes, and acute kudzu root extract administration significantly blunted this response by ~50%. In mice chronically fed a kudzu-supplemented diet, glucose tolerance was improved, and acute treatment caused no additional improvement. Irrespective of treatment, all mice were normoglycemic at the start of each glucose challenge. Administration of insulin resulted in a larger decrease in blood glucose in chronic kudzu-supplemented compared to control mice. Co-administration of phloridzin (a specific inhibitor of SGLT-mediated glucose uptake), improved glucose tolerance in acutely kudzu-treated mice but had no significant effect on glucose tolerance in chronically treated mice. These results indicate that both acute and chronic administration of kudzu root extract improves glucose tolerance in a normal glycemic mouse strain and that the effects of chronic kudzu feeding may be mediated, in part, by enhanced insulin sensitivity (chronic) and inhibition of sodium dependent glucose transport.

  13. Acute and Chronic Kudzu Improves Plasma Glucose Tolerance in Non-Diabetic CD-1 Mice

    PubMed Central

    Carlson, Scott; Prasain, Jeevan K.; Peng, Ning; Dai, Yanying; Wyss, J. Michael

    2016-01-01

    Previous studies demonstrate that kudzu root extract and its major isoflavone (puerarin) improve glucose metabolism in animal models of insulin resistance and type 2 diabetes; however, these beneficial effects have not been investigated in normal glycemic mice. The present study investigates the effect of acute and chronic kudzu root extract supplementation on glucose tolerance in normoglycemic CD-1 mice. Male, adult CD-1 mice were fed a phytoestrogen-free diet containing 0.2% or 0.0% kudzu root extract for 6 weeks. Thereafter, they were acutely administered kudzu root extract (75 mg/kg BW; oral) or vehicle followed by a glucose challenge (2 g/kg BW; oral). In control fed mice, the acute glucose challenge increased blood glucose ~300% after 30 minutes, and acute kudzu root extract administration significantly blunted this response by ~50%. In mice chronically fed a kudzu-supplemented diet, glucose tolerance was improved, and acute treatment caused no additional improvement. Irrespective of treatment, all mice were normoglycemic at the start of each glucose challenge. Administration of insulin resulted in a larger decrease in blood glucose in chronic kudzu-supplemented compared to control mice. Co-administration of phloridzin (a specific inhibitor of SGLT-mediated glucose uptake), improved glucose tolerance in acutely kudzu-treated mice but had no significant effect on glucose tolerance in chronically treated mice. These results indicate that both acute and chronic administration of kudzu root extract improves glucose tolerance in a normal glycemic mouse strain and that the effects of chronic kudzu feeding may be mediated, in part, by enhanced insulin sensitivity (chronic) and inhibition of sodium dependent glucose transport.

  14. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats.

    PubMed

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V; Gydesen, Sofie; Ottosen, Ida; Henriksen, Jan Erik; Beck-Nielsen, Henning; Christiansen, Claus; Karsdal, Morten A; Henriksen, Kim

    2014-08-15

    We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ. Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma glucoregulatory hormones and pancreatic insulin content were analyzed. Oral sCT treatment induced a pronounced anorectic action during the 7 days lead-in period and markedly reduced food intake and body weight in conjunction with improved glucose homeostasis. During the maintenance period, oral sCT normalized food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes.

  15. The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum

    PubMed Central

    Knudsen, Sine H.; Karstoft, Kristian; Pedersen, Bente K.; van Hall, Gerrit; Solomon, Thomas P. J.

    2014-01-01

    Abstract We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty‐four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age: 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m2, P > 0.05) underwent a 180‐min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6‐2H2]glucose and ingestion of [U‐13C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials, plasma glucose concentrations and kinetics, insulin, C‐peptide, and glucagon were measured. Rates (mg kg−1 min−1) of glucose appearance from endogenous (RaEndo) and exogenous (oral glucose; RaOGTT) sources, and glucose disappearance (Rd) were determined. We found that exercise increased RaEndo, RaOGTT, and Rd (all P < 0.0001) in all groups with a tendency for a greater (~20%) peak RaOGTT value in NGT subjects when compared to IGT and T2D subjects. Accordingly, following exercise, the plasma glucose concentration during the OGTT was increased in NGT subjects (P < 0.05), while unchanged in subjects with IGT and T2D. In conclusion, while a single bout of moderate‐intensity exercise increased the postprandial glucose response in NGT subjects, glucose tolerance following exercise was preserved in the two hyperglycemic groups. Thus, postprandial plasma glucose responses immediately following exercise are dependent on the underlying degree of glycemic control. PMID:25168869

  16. Hepatic overexpression of a constitutively active form of liver glycogen synthase improves glucose homeostasis.

    PubMed

    Ros, Susana; Zafra, Delia; Valles-Ortega, Jordi; García-Rocha, Mar; Forrow, Stephen; Domínguez, Jorge; Calbó, Joaquim; Guinovart, Joan J

    2010-11-26

    In this study, we tested the efficacy of increasing liver glycogen synthase to improve blood glucose homeostasis. The overexpression of wild-type liver glycogen synthase in rats had no effect on blood glucose homeostasis in either the fed or the fasted state. In contrast, the expression of a constitutively active mutant form of the enzyme caused a significant lowering of blood glucose in the former but not the latter state. Moreover, it markedly enhanced the clearance of blood glucose when fasted rats were challenged with a glucose load. Hepatic glycogen stores in rats overexpressing the activated mutant form of liver glycogen synthase were enhanced in the fed state and in response to an oral glucose load but showed a net decline during fasting. In order to test whether these effects were maintained during long term activation of liver glycogen synthase, we generated liver-specific transgenic mice expressing the constitutively active LGS form. These mice also showed an enhanced capacity to store glycogen in the fed state and an improved glucose tolerance when challenged with a glucose load. Thus, we conclude that the activation of liver glycogen synthase improves glucose tolerance in the fed state without compromising glycogenolysis in the postabsorptive state. On the basis of these findings, we propose that the activation of liver glycogen synthase may provide a potential strategy for improvement of glucose tolerance in the postprandial state.

  17. Glucose-dependent insulinotropic polypeptide confers early phase insulin release to oral glucose in rats: demonstration by a receptor antagonist.

    PubMed

    Lewis, J T; Dayanandan, B; Habener, J F; Kieffer, T J

    2000-10-01

    A novel GIP receptor antagonist was developed to evaluate the acute role of glucose-dependent insulinotropic polypeptide (GIP) in the insulin response to oral glucose in rats. Antisera to an extracellular epitope of the GIP receptor (GIPR) detected immunoreactive GIPR on rat pancreatic beta-cells. Purified GIPR antibody (GIPR Ab) specifically displaced GIP binding to the receptor and blocked GIP-mediated increases in intracellular cAMP. When delivered to rats by ip injection, GIPR Ab had a half-life of approximately 4 days. Treatment with GIPR Ab (1 microg/g BW) blocked the potentiation of glucose-stimulated insulin secretion by GIP (60 pmol) but not glucagon-like peptide-1 (GLP-1, 60 pmol) in anesthetized rats. The insulin response to oral glucose was delayed in conscious unrestrained rats that were pretreated with GIPR Ab. Plasma insulin levels were approximately 35% lower at 10 min in GIPR Ab treated animals compared with controls. As a result, the glucose excursion was greater in the GIPR Ab treated group. Fasting plasma glucose levels were not altered by GIPR Ab. We conclude that release of GIP following oral glucose may act as an anticipatory signal to pancreatic beta-cells to promote rapid release of insulin for glucose disposal.

  18. 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.

  19. Improving oral hygiene for patients.

    PubMed

    Bonetti, Debbie; Hampson, Victoria; Queen, Kerry; Kirk, Donna; Clarkson, Jan; Young, Linda

    2015-01-13

    Systematic reviews and patient safety initiatives recommend that oral hygiene should be part of routine patient care. However, evidence suggests it is often neglected in hospitals and care homes. Research recommends encouraging beliefs that support oral hygiene, and teaching nurses appropriate skills, as necessary prerequisites to implementing best practice in hospital wards. This article describes a pilot study of an educational workshop on oral hygiene. Results from the pilot study suggest that this workshop is a feasible intervention for a service-wide trial. The literature suggests that other interventions are required to complement this approach if nurses are to make oral hygiene a priority in daily patient care.

  20. Milrinone efficiently potentiates insulin secretion induced by orally but not intravenously administered glucose in C57BL6J mice.

    PubMed

    Degerman, Eva; Manganiello, Vincent; Holst, Jens J; Ahrén, Bo

    2004-09-13

    To study the effect of phosphodiesterase (PDE) 3 inhibition on plasma insulin and glucose levels, the selective PDE 3 inhibitor milrinone (0.25, 1.0, and 2.5 mg/kg) was given orally to anesthetized CL57Bl/6J mice 10 min before a gastric glucose gavage (150 mg/mouse). It was found that milrinone augmented the glucose-mediated increase in plasma insulin at 1.0 and 2.5 mg/kg without, however, any improvement in glucose elimination. In contrast, when given 10 min before intravenous glucose (1 g/kg), milrinone (1 mg/kg) did not affect the insulin response to glucose. The increase in glucagon-like peptide-1 (GLP-1) levels after gastric glucose was not altered by milrinone. However, the PDE3 inhibitor augmented the insulin response to intravenous GLP-1 (2.8 nmol/kg). We therefore conclude that PDE3 inhibition by milrinone augments insulin secretion in vivo in mice after oral but not after intravenous glucose, which may be explained by enhanced response to the cAMP-dependent insulinotropic action of endogenously released GLP-1.

  1. [High intensity interval training improves glycemic control and aerobic capacity in glucose intolerant patients].

    PubMed

    Mancilla, Rodrigo; Torres, Paola; Álvarez, Cristian; Schifferli, Ingrid; Sapunar, Jorge; Díaz, Erik

    2014-01-01

    Proper exercise training modifies intra miocellular energy utilization, glucose transport and mitochondrial biogenesis. To determine the therapeutic effects of a high intensity intermittent training (HIIT) program on glucose homeostasis, physical fitness and body fat in glucose intolerant patients. Eighteen patients with overweight or obesity and glucose intolerance were invited to participate in an exercise program consisting in three sessions per week for 3 months. Ten participants aged 35 ± 13 years who attended > 26 of the planned 36 sessions, were considered as adherent to exercise. The other eight participants aged 37 ± 17 years, who attended to a mean of 13 sessions, were considered as non-adherent. Both groups had similar body weight, body mass index, body fat, plasma glucose 2 h after an oral glucose load and maximal oxygen uptake. All these variables were measured at the end of exercise intervention. Each session consisted of 1 min exercise of cycling at maximal intensity until muscle fatigue followed by 2 min rest, repeated 10 times. Among adherent participants, twelve weeks of HIIT improved significantly maximal oxygen uptake (6.1 + 3.6 mL/kg/min or 24.6%), reduced 2 h post load blood glucose (-33.7 + 47.9 mg/dL or -12.5%) and body fat (-4.3 + 5.6 kg). No significant changes were observed in the non-adherent group. HIIT exercise reduces blood glucose after an oral load in glucose intolerant patients.

  2. Activation of the gut calcium-sensing receptor by peptide agonists reduces rapid elevation of plasma glucose in response to oral glucose load in rats.

    PubMed

    Muramatsu, Maya; Hira, Tohru; Mitsunaga, Arimi; Sato, Eri; Nakajima, Shingo; Kitahara, Yoshiro; Eto, Yuzuru; Hara, Hiroshi

    2014-06-15

    The calcium-sensing receptor (CaSR) is expressed in various tissues, including the gastrointestinal tract. To investigate the role of gut CaSR on glycemic control, we examined whether single oral administration of CaSR agonist peptides affected the glycemic response in rats. Glucose tolerance tests were performed under oral or duodenal administration of various CaSR agonist peptides (γGlu-Cys, protamine, and poly-d-lysine hydrobromide) in conscious rats. Involvement of CaSR was determined by using a CaSR antagonist. Signaling pathways underlying CaSR agonist-modified glycemia were investigated using gut hormone receptor antagonists. The gastric emptying rate after the administration of CaSR agonist peptides was measured by the phenol red recovery method. Oral and duodenal administration of CaSR agonist peptides attenuated glycemic responses under the oral glucose tolerance test, but the administration of casein did not. The promotive effect on glucose tolerance was weakened by luminal pretreatment with a CaSR antagonist. Treatment with a 5-HT3 receptor antagonist partially diminished the glucose-lowering effect of peptides. Furthermore, the gastric emptying rate was decreased by duodenal administration of CaSR agonist peptides. These results demonstrate that activation of the gut CaSR by peptide agonists promotes glucose tolerance in conscious rats. 5-HT3 receptor and the delayed gastric emptying rate appear to be involved in the glucose-lowering effect of CaSR agonist peptides. Thus, activation of gut CaSR by dietary peptides reduces glycemic responses so that gut CaSR may be a potential target for the improvement of postprandial glycemia.

  3. Oral therapy in children with cholera: a comparison of sucrose and glucose electrolyte solutions.

    PubMed

    Sack, D A; Islam, S; Brown, K H; Islam, A; Kabir, A K; Chowdhury, A M; Ali, M A

    1980-01-01

    We performed a double-blind trial comparing sucrose electrolyte oral solution with glucose electrolyte oral solution in children less than 5 years of age with severe cholera-like diarrhea. Of 111 patients studied (102 with bacteriologically confirmed cholera), 55 received sucrose solution and 56 received glucose solution. The success rates, as defined by the absence of the need to give unscheduled intravenous therapy, were similar in the two groups (73% and 77% in the sucrose and glucose groups, respectively). There was no difference in purging rates between the two groups. The primary determinant of success for oral fluid regardless of the sugar was the purging rate. Sucrose malabsorption was responsible for oral therapy failure in one child. This study demonstrates that sucrose is an effective alternative to glucose in the oral therapy solution, but either must be used in conjunction with intravenous solution when treating severe dehydrating diarrhea.

  4. Nanoemulsion: for improved oral delivery of repaglinide.

    PubMed

    Akhtar, Juber; Siddiqui, Hefazat Hussain; Fareed, Sheeba; Badruddeen; Khalid, Mohammad; Aqil, Mohammed

    2016-07-01

    Repaglinide (RPG) is a fast-acting prandial glucose regulator. It acts by stimulating insulin release from pancreatic β-cells. Recurrent dosing of RPG before each meal is burdensome remedy. Hence the plan of the present study was to evaluate nanoemulsion as a hopeful carrier for RPG for persistent hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion to give improved biopharmaceutical properties as compared to the lipid-based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w of oil from the o/w nanoemulsion region of phase diagrams. The optimized nanoemulsion formulation constituted sefsol-218 (5% v/v) as an oil phase, 30% v/v of Tween-80 and transcutol as a surfactant and co-surfactant to restrain nanodroplet size and low viscosity and distilled water (65%). In vitro dissolution studies showed higher drug release (98.22%), finest droplet size (76.23 nm), slightest polydispersity value (0.183), least viscosity (21.45 cps) and immeasurable dilution capability from the nanoemulsion as compared with existing oral tablet formulation. The optimized RPG nanoemulsion formulation showed better hypoglycemic effect in comparison to tablet formulation in experimental diabetic rats. No significant variations were also observed in the optimized formulation when subjected to accelerated stability study at different temperature and relative humidity over a period of 3 months.

  5. Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats.

    PubMed

    Agil, Ahmad; Rosado, Isaac; Ruiz, Rosario; Figueroa, Adriana; Zen, Nourahouda; Fernández-Vázquez, Gumersindo

    2012-03-01

    The aim of this study was to investigate the effects of melatonin on glucose homeostasis in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups, each composed of ten rats: naive (N), vehicle treated (V), and melatonin treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. ZDF rats developed DM (fasting hyperglycemia, 460±39.8mg/dL; HbA(1) c 8.3±0.5%) with both insulin resistance (HOMA-IR 9.28±0.9 versus 1.2±0.1 in ZL) and decreased β-cell function (HOMA1-%B) by 75%, compared with ZL rats. Melatonin reduced fasting hyperglycemia by 18.6% (P<0.05) and HbA(1) c by 11% (P<0.05) in ZDF rats. Also, melatonin lowered insulinemia by 15.9% (P<0.05) and HOMA-IR by 31% (P<0.01) and increased HOMA1-%B by 14.4% (P<0.05). In addition, melatonin decreased hyperleptinemia by 34% (P<0.001) and raised hypoadiponectinemia by 40% (P<0.001) in ZDF rats. Moreover, melatonin reduced serum free fatty acid levels by 13.5% (P<0.05). These data demonstrate that oral melatonin administration ameliorates glucose homeostasis in young ZDF rats by improving both insulin action and β-cell function. These observations have implications on melatonin's possible use as a new pharmacologic therapy for improving glucose homeostasis and of obesity-related T2DM, in young subjects.

  6. Rosiglitazone improves glucose metabolism in obese adolescents with impaired glucose tolerance: a pilot study.

    PubMed

    Cali, Anna M G; Pierpont, Bridget M; Taksali, Sara E; Allen, Karin; Shaw, Melissa M; Savoye, Mary; Caprio, Sonia

    2011-01-01

    Impaired glucose tolerance (IGT) is a prediabetic state fueling the rising prevalence of type 2 diabetes mellitus (T2DM) in adolescents with marked obesity. Given the importance of insulin resistance, the poor β-cell compensation and the altered fat partitioning as underlying defects associated with this condition, it is crucial to determine the extent to which these underlying abnormalities can be reversed in obese adolescents. We tested, in a pilot study, whether rosiglitazone (ROSI) restores normal glucose tolerance (NGT) in obese adolescents with IGT by improving insulin sensitivity and β-cell function. In a small randomized, double-blind, placebo (PLA)-controlled study, lasting 4 months, 21 obese adolescents with IGT received either ROSI (8 mg daily) (n = 12, 5M/7F, BMI z-score 2.44 ± 0.11) or PLA (n = 9, 4M/5F, BMI z-score 2.41 ± 0.09). Before and after treatment, all subjects underwent oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, magnetic resonance imaging, and (1)H NMR assessment. After ROSI treatment, 58% of the subjects converted to NGT compared to 44% in the PLA group (P = 0.528). Restoration of NGT was associated with a significant increase in insulin sensitivity (P < 0.04) and a doubling in the disposition index (DI) (P < 0.04), whereas in the PLA group, these changes were not significant. The short-term use of ROSI appears to be safe in obese adolescents with IGT. ROSI restores NGT by increasing peripheral insulin sensitivity and β-cell function, two principal pathophysiological abnormalities of IGT.

  7. Quality Improvement Efforts in Pediatric Oral Health.

    PubMed

    Ng, Man Wai

    2016-04-01

    Quality improvement (QI) and measurement are increasingly used in health care to improve patient care and outcomes. Despite current barriers in oral health measurement, there are nascent QI and measurement efforts emerging. This paper describes the role that QI and measurement can play in improving oral health care delivery in clinical practice by presenting a QI initiative that aimed to test and implement a chronic disease management approach to address early childhood caries.

  8. Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load

    PubMed Central

    Walsh, Lauren K.; Restaino, Robert M.; Neuringer, Martha; Manrique, Camila; Padilla, Jaume

    2017-01-01

    Postprandial hyperglycemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. Herein we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, 1 hour, and 2 hours post an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized crossover design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycemia under the placebo condition (−32% at 1 hr and −28% at 2 hr post oral glucose load; p<0.05 from baseline) but not under the TUDCA condition (−4% at 1 hr and +0.3% at 2 hr post oral glucose load; p>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and TBARs remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycemia. PMID:27503949

  9. Even small interventions can improve oral health.

    PubMed

    Vega, Lina; Carberry, Frank J

    2013-01-01

    When resources are scarce, authors of articles appearing in health publications have questioned the effectiveness of traditional interventions as a means of improving oral health. The experience in Delicias, Honduras, indicates that the principles of BPOC (Basic Package of Oral Care) may provide quicker and better results.

  10. Cacao liquor procyanidin extract improves glucose tolerance by enhancing GLUT4 translocation and glucose uptake in skeletal muscle.

    PubMed

    Yamashita, Yoko; Okabe, Masaaki; Natsume, Midori; Ashida, Hitoshi

    2012-01-01

    Hyperglycaemia and insulin resistance are associated with the increased risk of the metabolic syndrome and other severe health problems. The insulin-sensitive GLUT4 regulates glucose homoeostasis in skeletal muscle and adipose tissue. In this study, we investigated whether cacao liquor procyanidin (CLPr) extract, which contains epicatechin, catechin and other procyanidins, improves glucose tolerance by promoting GLUT4 translocation and enhances glucose uptake in muscle cells. Our results demonstrated that CLPr increased glucose uptake in a dose-dependent manner and promoted GLUT4 translocation to the plasma membrane of L6 myotubes. Oral administration of a single dose of CLPr suppressed the hyperglycaemic response after carbohydrate ingestion, which was accompanied by enhanced GLUT4 translocation in ICR mice. These effects of CLPr were independent of α-glucosidase inhibition in the small intestine. CLPr also promoted GLUT4 translocation in skeletal muscle of C57BL/6 mice fed a CLPr-supplemented diet for 7 d. These results indicate that CLPr is a beneficial food material for improvement of glucose tolerance by promoting GLUT4 translocation to the plasma membrane of skeletal muscle.

  11. Oral dehydroepiandrosterone (DHEA) replacement in older adults: effects on central adiposity, glucose metabolism, and blood lipids

    PubMed Central

    Jankowski, Catherine M.; Gozansky, Wendolyn S.; Van Pelt, Rachael E.; Wolfe, Pamela; Schwartz, Robert S.; Kohrt, Wendy M.

    2011-01-01

    Objective The aim was to determine the effects of dehydroepiandrosterone (DHEA) therapy on changes in central adiposity, insulin action, and blood lipids. Many of the actions of DHEA in humans are thought to be mediated through its conversion to sex hormones, which are modulators of adiposity, muscularity, and insulin sensitivity. The effects of DHEA replacement on regional tissue composition, glucose metabolism, and blood lipid profile in older adults have been inconsistent. Design a randomized, double-blinded, placebo-controlled trial. The intervention was oral DHEA 50 mg/d or placebo for 12 months. Participants 58 women and 61 men, aged 60–88 yr, with low serum DHEA sulfate (DHEAS) levels at study entry. Measurements Computed tomography measures of abdominal fat areas, thigh muscle and fat areas, DXA-derived trunk fat mass, serum glucose and insulin responses to an oral glucose challenge, and fasted serum total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides were assessed before and after the intervention. Results There were no significant (P > 0.05) differences between the DHEA and placebo groups in the changes in regional tissue composition or glucose metabolism. HDL-cholesterol (P =0.01) and fasted triglycerides (P =0.02) decreased in women and men taking DHEA. Conclusion Restoring serum DHEAS levels in older adults to young adult levels for 1 year does not appear to reduce central adiposity or improve insulin action. The benefit of DHEA on decreasing serum triglycerides must be weighed against the HDL-lowering effect. PMID:21521341

  12. Serum progranulin concentrations are not responsive during oral lipid tolerance test and oral glucose tolerance test.

    PubMed

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2015-07-01

    The postprandial regulation of progranulin by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of progranulin in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn at 0 hours (h) (fasting) and at 2, 4, and 6 h in OLTT or 1 and 2 h in OGTT. A novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of progranulin were measured by enzyme-linked immunosorbent assay (ELISA). Circulating progranulin levels remained unchanged during OLTT and OGTT. Fasting progranulin levels ranged between 31.3±8.7 and 40.6±7.7 ng/ml and were not different in subgroups addressing BMI, gender, family history, smoking habits, and hormonal contraception. There was a reciprocal correlation of progranulin with HDL (negative) and LDL cholesterol levels (positive). In healthy adults, fasting and postprandial circulating progranulin levels are not different in BMI subgroups. Oral uptake of carbohydrates and lipids does not influence circulating progranulin levels in a short-term manner. A postprandial and short-term regulation of this adipokine is absent, at least in healthy subjects. There is a negative correlation of progranulin with HDL cholesterol, but a positive correlation with LDL cholesterol. This reciprocal association might be of physiological importance for an individual's atherosclerotic risk.

  13. The incretin effect in cats: comparison between oral glucose, lipids, and amino acids.

    PubMed

    Gilor, C; Graves, T K; Gilor, S; Ridge, T K; Weng, H-Y; Dossin, O

    2011-05-01

    Incretin hormones are secreted from the intestines in response to specific nutrients. They potentiate insulin secretion and have other beneficial effects in glucose homeostasis. We aimed to study the incretin effect in cats and to compare the effect of oral glucose, lipids, or amino acids on serum concentrations of insulin, total glucose-dependent insulinotropic peptide (GIP) and total glucagon-like peptide 1 (GLP-1). Ten healthy cats were used in a repeated measures design. Glucose, lipid, or amino acids were administered through nasoesophageal tubes on separate days. Blood glucose (BG) concentrations were matched between experiments by measuring BG every 5 min and infusing glucose intravenously at a changing rate. Intravenous glucose infusion with no prior treatment served as control. The incretin effect was estimated as the difference in insulin area under the curve (AUC) after oral compared with intravenous glucose. Temporal changes and total amount of hormone secretions were compared between treatment groups with the use of mixed models. Total glucose infused (TGI) at a mean dose of 0.49 g/kg resulted in slightly higher BG compared with 1 g/kg oral glucose (P = 0.038), but insulin concentrations were not significantly different (P = 0.367). BG and the TGI were not significantly different after the 3 oral challenges. Total GIP AUC was larger after lipids compared with amino acids (P = 0.0012) but GIP concentrations did not increase after oral glucose. Insulin and GIP concentrations were positively correlated after lipid (P < 0.001) and amino acids (P < 0.001) stimulations, respectively, but not after oral glucose stimulation. Total GLP-1 AUC was similar after all three oral stimulations. Insulin and GLP-1 concentrations were positively correlated after glucose (P = 0.001), amino acids (P < 0.001), or lipids (P = 0.001) stimulations. Our data indirectly support an insulinotropic effect of GIP and GLP-1. Potentiation of insulin secretion after oral glucose is

  14. [Role of classical oral glucose-lowering medications in current treatment].

    PubMed

    Carramiñana Barrera, F C

    2014-07-01

    Classical oral glucose were discovered in the mid twentieth century. Despite the time elapsed since then and the lack of large studies to support the use of some of these drugs, they continue to be employed, are indicated in all clinical practice guidelines and consensus documents and, overall, remain among the most widely prescribed drugs in the national health system. The main arguments for their continued use are their widespread and prolonged prescription, their effectiveness, and cost. Their main disadvantages have always been and continue to be their adverse gastrointestinal effects, weight gain, the risk of hypoglycemia and other adverse effects, which have encouraged the development of new glucose-lowering drugs with an improved pharmacological profile that would cover the various mechanisms of hyperglycemia. Currently, deep knowledge of glucose-lowering drugs is required in the patient-centered management of diabetes. Furthermore, this knowledge should be adapted to each individual patient to acquire the experience necessary to achieve effective metabolic control, delay the development of chronic complications, and improve the quality of life and life expectancy of patients with diabetes.

  15. The "muffin test"--an alternative to the oral glucose tolerance test for detecting impaired glucose tolerance.

    PubMed

    Traub, Michael L; Jain, Akas; Maslow, Bat-Sheva; Pal, Lubna; Stein, Daniel T; Santoro, Nanette; Freeman, Ruth

    2012-01-01

    The aim of this study was to compare the effectiveness of the "muffin test" (MT) with that of the oral glucose tolerance test (OGTT) in diagnosing impaired glucose tolerance (IGT). This is a cross-sectional study in a single academic institution. The participants were 73 women aged 42 to 58 years, less than 36 months after menopause, recruited for the Kronos Early Estrogen Prevention Study Trial. After a 10-hour fasting blood draw, the participants were provided a muffin and a beverage. Two-hour glucose levels were assessed. A subset underwent metabolic testing consisting of an OGTT (n = 12) and a mixed-meal tolerance test (n = 10). The main outcome measures were the prevalence of IGT and 2-hour glucose measurements after each testing method. Two-hour glucose levels were linearly related to fasting values by multivariable linear regression. This association was exaggerated in overweight (body mass index, 25 kg/m2) women (coefficient, 1.43; P < 0.001). Two-hour OGTT and MT glucose levels were comparable (P > 0.05); 2-hour glucose levels after OGTT were slightly lower than after the mixed-meal tolerance test (P < 0.05). The prevalence of IGT was 11% (8 of 73). Fasting plasma glucose alone would have missed 63% of cases (five of eight cases). The MT demonstrated 100% sensitivity and specificity for diagnosing IGT compared with the gold standard OGTT. This small pilot study should be confirmed in a larger prospective group of participants.

  16. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    PubMed

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice.

  17. Simulation of oral glucose tolerance tests and the corresponding isoglycemic intravenous glucose infusion studies for calculation of the incretin effect.

    PubMed

    Kim, Myeungseon; Oh, Tae Jung; Lee, Jung Chan; Choi, Karam; Kim, Min Young; Kim, Hee Chan; Cho, Young Min; Kim, Sungwan

    2014-03-01

    The incretin effect, which is a unique stimulus of insulin secretion in response to oral ingestion of nutrients, is calculated by the difference in insulin secretory responses from an oral glucose tolerance test (OGTT) and a corresponding isoglycemic intravenous glucose infusion (IIGI) study. The OGTT model of this study, which is individualized by fitting the glucose profiles during an OGTT, was developed to predict the glucose profile during an IIGI study in the same subject. Also, the model predicts the insulin and incretin profiles during both studies. The incretin effect, estimated by simulation, was compared with that measured by physiologic studies from eight human subjects with normal glucose tolerance, and the result exhibited a good correlation (r > 0.8); the incretin effect from the simulation was 56.5% ± 10.6% while the one from the measured data was 52.5% ± 19.6%. In conclusion, the parameters of the OGTT model have been successfully estimated to predict the profiles of both OGTTs and IIGI studies. Therefore, with glucose data from the OGTT alone, this model could control and predict the physiologic responses, including insulin secretion during OGTTs and IIGI studies, which could eventually eliminate the need for complex and cumbersome IIGI studies in incretin research.

  18. Formulation strategies to improve oral peptide delivery.

    PubMed

    Maher, Sam; Ryan, Ben; Duffy, Aoife; Brayden, David J

    2014-05-01

    Delivery of peptides by the oral route greatly appeals due to commercial, patient convenience and scientific arguments. While there are over 60 injectable peptides marketed worldwide, and many more in development, most delivery strategies do not yet adequately overcome the barriers to oral delivery. Peptides are sensitive to chemical and enzymatic degradation in the intestine, and are poorly permeable across the intestinal epithelium due to sub-optimal physicochemical properties. A successful oral peptide delivery technology should protect potent peptides from presystemic degradation and improve epithelial permeation to achieve a target oral bioavailability with acceptable intra-subject variability. This review provides a comprehensive up-to-date overview of the current status of oral peptide delivery with an emphasis on patented formulations that are yielding promising clinical data.

  19. Effects of Exercise Intensity on Postprandial Improvement in Glucose Disposal and Insulin Sensitivity in Prediabetic Adults

    PubMed Central

    Rynders, Corey A.; Weltman, Judy Y.; Jiang, Boyi; Breton, Marc; Patrie, James; Barrett, Eugene J.

    2014-01-01

    Background: A single bout of exercise improves postprandial glycemia and insulin sensitivity in prediabetic patients; however, the impact of exercise intensity is not well understood. The present study compared the effects of acute isocaloric moderate (MIE) and high-intensity (HIE) exercise on glucose disposal and insulin sensitivity in prediabetic adults. Methods: Subjects (n = 18; age 49 ± 14 y; fasting glucose 105 ± 11 mg/dL; 2 h glucose 170 ± 32 mg/dL) completed a peak O2 consumption/lactate threshold (LT) protocol plus three randomly assigned conditions: 1) control, 1 hour of seated rest, 2) MIE (at LT), and 3) HIE (75% of difference between LT and peak O2 consumption). One hour after exercise, subjects received an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and C-peptide concentrations were sampled at 5- to 10-minute intervals at baseline, during exercise, after exercise, and for 3 hours after glucose ingestion. Total, early-phase, and late-phase area under the glucose and insulin response curves were compared between conditions. Indices of insulin sensitivity (SI) were derived from OGTT data using the oral minimal model. Results: Compared with control, SI improved by 51% (P = .02) and 85% (P < .001) on the MIE and HIE days, respectively. No differences in SI were observed between the exercise conditions (P = .62). Improvements in SI corresponded to significant reductions in the glucose, insulin, and C-peptide area under the curve values during the late phase of the OGTT after HIE (P < .05), with only a trend for reductions after MIE. Conclusion: These results suggest that in prediabetic adults, acute exercise has an immediate and intensity-dependent effect on improving postprandial glycemia and insulin sensitivity. PMID:24243632

  20. The Effect of Environmental Temperature on Glucose and Insulin After an Oral Glucose Tolerance Test in Healthy Young Men.

    PubMed

    Dumke, Charles L; Slivka, Dustin R; Cuddy, John S; Hailes, Walter S; Rose, Shawn M; Ruby, Brent C

    2015-09-01

    The purpose of this study was to compare glucose and insulin responses during an oral glucose tolerance test (OGTT) in cold (C), neutral (N), and hot (H) environments. Eleven males completed three 4-hour climate-controlled OGTT trials (C, 7.2°C; N, 22°C; and H, 43°C). Participants remained semireclined for 60 minutes before ingesting a 1.8 g/kg glucose beverage. Skin and rectal core temperatures were continuously monitored. Blood was collected just before glucose ingestion (time 0) and at 15, 30, 60, 90, 120, and 180 minutes, and analyzed for serum glucose, insulin, hematocrit, and hemoglobin. Expired gases were collected upon entering the chamber (-60 minutes), before glucose ingestion (0 minutes), and at 60, 120, and 180 minutes to determine V(O2) and respiratory exchange ratio. Rectal core temperature was greater in the H condition compared with both C and N (P < .001). Rectal core temperature was not different between C and N, whereas skin temperature was different across all trials (H greater than N greater than C). The V(O2) was greater in C than in both H and N during all time points. Carbohydrate oxidation was greater in C compared with H and N (P < 0.001). Glucose was higher during H compared with C and N (P ≤ 0.002). Glucose was elevated in C compared with N. Insulin was higher in H compared with C (P = 0.009). Area under the curve for serum glucose was greater in H compared with C and N (P ≤ 0.001); however, there was no significant difference in area under the curve for insulin. These data indicate that after an OGTT, glucose and insulin are elevated in a hot environment. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  1. Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test.

    PubMed

    Salinari, Serenella; Bertuzzi, Alessandro; Mingrone, Geltrude

    2011-06-01

    The rate of appearance (R(a)) of exogenous glucose in plasma after glucose ingestion is presently measured by tracer techniques that cannot be used in standard clinical testing such as the oral glucose tolerance test (OGTT). We propose a mathematical model that represents in a simple way the gastric emptying, the transport of glucose along the intestinal tract, and its absorption from gut lumen into portal blood. The model gives the R(a) time course in terms of parameters with a physiological counterpart and provides an expression for the release of incretin hormones as related to glucose transit into gut lumen. Glucose absorption was represented by assuming two components related to a proximal and a distal transporter. Model performance was evaluated by numerical simulations. The model was then validated by fitting OGTT glucose and GLP-1 data in healthy controls and type 2 diabetic patients, and useful information was obtained for the rate of gastric emptying, the rate of glucose absorption, the R(a) profile, the insulin sensitivity, and the glucose effectiveness. Model-derived estimates of insulin sensitivity were well correlated (r = 0.929 in controls and 0.886 in diabetic patients) to data obtained from the euglycemic hyperinsulinemic clamp. Although the proposed OGTT analysis requires the measurement of an additional hormone concentration (GLP-1), it appears to be a reasonable choice since it avoids complex and expensive techniques, such as isotopes for glucose R(a) measurement and direct assessment of gastric emptying and intestinal transit, and gives additional correlated information, thus largely compensating for the extra expense.

  2. Fermentable dietary fiber increases GLP-1 secretion and improves glucose homeostasis despite increased intestinal glucose transport capacity in healthy dogs.

    PubMed

    Massimino, S P; McBurney, M I; Field, C J; Thomson, A B; Keelan, M; Hayek, M G; Sunvold, G D

    1998-10-01

    Ileal proglucagon gene expression and postprandial plasma concentrations of proglucagon-derived peptides are reported to change with the type and quantity of dietary fiber ingested by rats. Within the intestine, proglucagon encodes several proglucagon-derived peptides known to modulate intestinal absorption capacity and pancreatic insulin secretion. To determine whether the chronic ingestion of fermentable dietary fiber regulates the expression and synthesis of proglucagon-derived peptides in the distal intestine to modulate glucose homeostasis, the following study was conducted: 16 adult dogs (23 +/- 2 kg) were fed isoenergetic, isonitrogenous diets containing a mixture of high fermentable dietary fibers (HFF) or low fermentable (LFF) wood cellulose for 14 d in a randomized cross-over design. Food was withheld for 16 h before an oral glucose tolerance test was conducted supplying 2 g of glucose/kg body wt, and peripheral blood was collected via a hind-leg catheter at 0, 15, 30, 45, 60, 90 and 120 min for plasma glucose, insulin and glucagon-like peptide-1(7-36)NH2 (GLP-1) analyses. Intestinal samples were collected after the second dietary treatment. Ileal proglucagon mRNA, intestinal (GLP-1) concentrations and the integrated area under the curves (AUC) for plasma GLP-1 and insulin were greater and plasma glucose AUC was reduced when dogs were fed the HFF diet compared to the LFF diet (P < 0.05). Intestinal villi heights, brush border and basolateral glucose transporter protein abundance and jejunal transport capacities were significantly greater when dogs were fed the HFF diet than when fed the LFF diet. In conclusion, improvements in glucose homeostasis are observed in healthy dogs when they ingest fermentable fibers.

  3. Voluntary running improves glucose tolerance and insulin resistance in female spontaneously hypertensive rats.

    PubMed

    LaPier, T L; Swislocki, A L; Clark, R J; Rodnick, K J

    2001-07-01

    We evaluated the effects of voluntary exercise training on glucose metabolism and measures of insulin sensitivity in female spontaneously hypertensive rats (SHR). Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. Exercising SHR were housed in running wheels for 8 weeks (SHRx8) or 16 weeks (SHRx16). At 22 weeks of age, we measured systolic blood pressure, performed oral glucose tolerance tests, and determined hexokinase activity and glucose transporter (GLUT) 4 content in skeletal muscle to assess intracellular glucose metabolism. Blood pressure was lower in WKY (139+/-12 mm Hg) than untrained SHR (216+/-13 mm Hg). Exercise training caused a reduction in blood pressure (-18 mm Hg) for SHRx8. After a brief (5-h) fast, serum glucose was lower in SHR that exercised compared with sedentary SHR, whereas insulin concentrations were identical between all SHR and WKY. Corresponding free fatty acids (FFA) were twofold higher in SHR than in WKY. In response to glucose, SHR demonstrated higher glucose and FFA responses, with exercise decreasing the glucose values in a dose-dependent manner. Although the insulin response was comparable in all groups, the glucose-to-insulin ratio was higher in SHR, indicating a relative insulin resistance for both glucose disposal and suppression of free fatty acids. Hexokinase activity and GLUT4 content were elevated 1.4- and 2.8-fold, respectively, in plantaris muscle of SHRx16, suggesting an improvement in the capacity for glucose transport and phosphorylation with exercise. These results provide evidence that voluntary running in female SHR lowers blood pressure and selectively increases glucose uptake and insulin action, but not suppression of FFA.

  4. Pancreatic islet hormone response to oral glucose in morbidly obese patients.

    PubMed Central

    Sirinek, K R; O'Dorisio, T M; Howe, B; McFee, A S

    1985-01-01

    Pancreatic islet peptides, as well as other gastrointestinal hormones, have been implicated in both the pathogenesis of obesity and the etiology of associated metabolic derangements. This study evaluated the pancreatic islet and gastrointestinal (GI) hormone response to oral glucose in 20 morbidly obese (151% above ideal body weight) patients. Glucose intolerance, hyperinsulinism, and exaggerated gastric inhibitory polypeptide (GIP) release occurred following glucose ingestion. Significant release of PP occurred in 14 patients, while only six patients had release of somatostatin. No significant changes in plasma concentrations of glucagon occurred. Since GIP is insulinotropic in the presence of hyperglycemia, the hyperinsulinism of morbid obesity may be secondary to the abnormally high glucose-stimulated GIP levels in these patients. Failure of glucagon suppression in response to oral glucose many contribute to the hyperglycemia noted. Somatostatin and pancreatic polypeptide may be responsible for some of the metabolic derangements of morbid obesity. PMID:2860876

  5. Failure of Hyperglycemia and Hyperinsulinemia to Compensate for Impaired Metabolic Response to an Oral Glucose Load

    PubMed Central

    Hussain, M; Janghorbani, M; Schuette, S; Considine, RV; Chisholm, RL; Mather, KJ

    2014-01-01

    Objective To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. Methods Non-obese, obese normoglycemic and obese Type 2 diabetic subjects were studied on 2 consecutive days. A 75g oral glucose load spiked with 13C-glucose was administered, measuring exhaled breath 13CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath 13CO2. Results Breath 13CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. Conclusions Augmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes. PMID:25511878

  6. Oral Motor Intervention Improved the Oral Feeding in Preterm Infants

    PubMed Central

    Tian, Xu; Yi, Li-Juan; Zhang, Lei; Zhou, Jian-Guo; Ma, Li; Ou, Yang-Xiang; Shuai, Ting; Zeng, Zi; Song, Guo-Min

    2015-01-01

    Abstract Oral feeding for preterm infants has been a thorny problem worldwide. To improve the efficacy of oral feeding in preterm infants, oral motor intervention (OMI), which consists of nonnutritive sucking, oral stimulation, and oral support, was developed. Published studies demonstrated that OMI may be as an alternative treatment to solve this problem; however, these results remain controversial. We conducted a meta-analysis with trial sequential analysis (TSA) to objectively evaluate the potential of OMI for improving the current status of oral feeding in preterm infants. A search of PubMed, EMBASE, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed to capture relevant citations until at the end of October, 2014. Lists of references of eligible studies and reviews were also hand-checked to include any latent studies. Two independent investigators screened literature, extracted data, and assessed the methodology, and then a meta-analysis and TSA was performed by using Reviewer Manager (RevMan) 5.3 and TSA 0.9 beta, respectively. A total of 11 randomized controlled trials (RCTs), which included 855 participants, were incorporated into our meta-analysis. The meta-analyses suggested that OMI is associated with the reduced transition time (ie, the time needed from tube feeding to totally oral feeding) (mean difference [MD], −4.03; 95% confidence interval [CI], −5.22 to −2.84), shorten hospital stays (MD, −3.64; 95% CI, −5.57 to −1.71), increased feeding efficiency (MD, 0.08; 95% CI, 0.36–1.27), and intake of milk (MD, 0.14; 95% CI, 0.06–0.21) rather than weight gain. Results of TSA for each outcomes of interest confirmed these pooled results. With present evidences, OMI can be as an alternative to improve the condition of transition time, length of hospital stays, feeding efficiency, and intake of milk in preterm infants. However, the pooled results may be impaired due to low quality included, and thus

  7. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.

    PubMed

    Merovci, Aurora; Solis-Herrera, Carolina; Daniele, Giuseppe; Eldor, Roy; Fiorentino, Teresa Vanessa; Tripathy, Devjit; Xiong, Juan; Perez, Zandra; Norton, Luke; Abdul-Ghani, Muhammad A; DeFronzo, Ralph A

    2014-02-01

    Chronic hyperglycemia impairs insulin action, resulting in glucotoxicity, which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors. Here, we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes. Eighteen diabetic men were randomized to receive either dapagliflozin (n = 12) or placebo (n = 6) for 2 weeks. We measured insulin-mediated whole body glucose uptake and endogenous glucose production (EGP) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique. Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose. Insulin-mediated tissue glucose disposal increased by approximately 18% after 2 weeks of dapagliflozin treatment, while placebo-treated subjects had no change in insulin sensitivity. Surprisingly, following dapagliflozin treatment, EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration. Together, our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity. However, glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP. These results provide support for the glucotoxicity hypothesis, which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes.

  8. Improved Starch Digestion of Sucrase-deficient Shrews Treated With Oral Glucoamylase Enzyme Supplements.

    PubMed

    Nichols, Buford L; Avery, Stephen E; Quezada-Calvillo, Roberto; Kilani, Shadi B; Lin, Amy Hui-Mei; Burrin, Douglas G; Hodges, Benjamin E; Chacko, Shaji K; Opekun, Antone R; Hindawy, Marwa El; Hamaker, Bruce R; Oda, Sen-Ichi

    2017-08-01

    Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase-deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with congenital sucrase-isomaltase deficiency.Starch digestion is much more complex than sucrose digestion. Six enzyme activities, 2 α-amylases (Amy), and 4 mucosal α-glucosidases (maltases), including maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose. Amy breaks down insoluble starch to soluble dextrins; mucosal Mgam and Si can either directly digest starch to glucose or convert the post-α-amylolytic dextrins to glucose. Starch digestion is reduced because of sucrase deficiency and oral glucoamylase enzyme supplement can correct the starch maldigestion. The aim of the present study was to measure glucogenesis in suc/suc shrews after feeding of starch and improvement of glucogenesis by oral glucoamylase supplements. Sucrase mutant (suc/suc) and heterozygous (+/suc) shrews were fed with C-enriched starch diets. Glucogenesis derived from starch was measured as blood C-glucose enrichment and oral recombinant C-terminal Mgam glucoamylase (M20) was supplemented to improve starch digestion. After feedings, suc/suc and +/suc shrews had different starch digestions as shown by blood glucose enrichment and the suc/suc had lower total glucose concentrations. Oral supplements of glucoamylase increased suc/suc total blood glucose and quantitative starch digestion to glucose. Sucrase deficiency, in this model of congenital sucrase-isomaltase deficiency, reduces blood glucose response to starch feeding. Supplementing the diet with oral recombinant glucoamylase significantly improved starch digestion in the sucrase-deficient shrew.

  9. The shape of the glucose response curve during an oral glucose tolerance test heralds biomarkers of type 2 diabetes risk in obese youth

    USDA-ARS?s Scientific Manuscript database

    The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against m...

  10. Response of incretins (GIP and GLP-1) to an oral glucose load in female and male subjects with normal glucose tolerance.

    PubMed

    Matsuo, Toshihiro; Kusunoki, Yoshiki; Katsuno, Tomoyuki; Ikawa, Takashi; Akagami, Takafumi; Murai, Kazuki; Miuchi, Masayuki; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi

    2014-11-01

    The aim of this study was to analyze the blood glucose profile and the response of incretins in healthy young subjects by the 75 g oral glucose tolerance test (OGTT). We first reported that plasma glucose and GIP levels were higher in males during the early phase of the OGTT.

  11. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

    PubMed

    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-03-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms.

    PubMed

    Bonuccelli, Sandra; Muscelli, Elza; Gastaldelli, Amalia; Barsotti, Elisabetta; Astiarraga, Brenno D; Holst, Jens J; Mari, Andrea; Ferrannini, Ele

    2009-08-01

    Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min (Study I). The protocol was repeated on a separate day (Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. beta-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-(2)H(2)]glucose and labeling of the 2 glucose loads with [1-(2)H]glucose and [U-(13)C]glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 +/- 2% (P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 +/- 4.3 vs. 42.8 +/- 5.1 nmol/m(2), P = 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 +/- 0.02- vs. 0.92 +/- 0.02-fold, P = 0.006), the increment being higher in Study II (+36 +/- 5%) than Study I (+19 +/- 6%, P < 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rho=0.60, P = 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 +/- 6 g for the first load and 52 +/- 5 g for the second load (P = not significant). Fasting endogenous glucose production [13.3 +/- 0.6 micromol x min(-1) x kg fat-free mass (FFM)(-1)] averaged 6.0 +/- 3.8 micromol x min(-1) x kg FFM(-1) between 0 and 180 min and 1.7 +/- 2.6 between 180 and 360 min (P < 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect.

  13. Oral glucose tolerance test reduces arterial baroreflex sensitivity in older adults.

    PubMed

    Madden, Kenneth M; Tedder, Gale; Lockhart, Chris; Meneilly, Graydon S

    2008-03-01

    Although postprandial decreases in blood pressure are a common cause of syncope in the older adult population, the postprandial effects of the oral glucose tolerance test on blood pressure and the arterial baroreflex remain poorly characterized in older adults. Therefore, arterial blood pressure and the arterial baroreflex were studied in 19 healthy older adults (mean age 71.7 +/- 1.1 years) who were given a standardized oral glucose load (75 g) or an isovolumetric sham drink during 2 separate sessions. All measures were taken for 120 min after treatment. Baroreflex function was assessed by using the spontaneous baroreflex method (baroreflex sensitivity, BRS). Subjects demonstrated a decrease in BRS after oral glucose that was not seen in the placebo session (two-way analysis of variance, p = 0.04). There was no significant change in systolic, mean, or diastolic blood pressure; together with a drop in BRS, this resulted in a significant tachycardia post glucose (two-way analysis of variance, p < 0.001). We conclude that healthy older adults can successfully maintain blood pressure during an oral glucose tolerance test despite a decrease in arterial BRS. Decreased BRS resulted in a tachycardic response to glucose.

  14. Colestimide improves glycemic control via hepatic glucose production in db/db mice.

    PubMed

    Yamakawa, Tadashi; Ogihara, Kikumi; Utsunomiya, Hirotoshi; Muraoka, Tomonori; Kadonosono, Kazuaki; Terauchi, Yasuo

    2014-01-01

    The objective of this study was to assess the chronic effects of a bile acid sequestrant, colestimide, on glucose metabolism. After db/db mice were fed a diet containing colestimide or cholic acid (CA) for 12 weeks, we investigated the impact of these agents on glucose and lipid metabolism. Colestimide significantly reduced the elevated fasting blood glucose level (p<0.01), and CA even more markedly reduced fasting blood glucose. The blood glucose level after an oral glucose load was significantly lower in the CA group than in the control group, but the colestimide group showed no significant difference. The insulin response to a glucose load was abolished in the control and colestimide groups. A hyperinsulinemic-euglycemic clamp study revealed that colestimide significantly improved the GIR (p=0.013). Hepatic EGP and Rd were also improved by colestimide, suggesting that it alleviated insulin resistance by suppressing hepatic glucose production and increasing peripheral glucose usage. CA significantly increased both the weight and cholesterol content of the liver, while colestimide reduced these parameters. Colestimide suppressed hepatic gene expression of SHP, but enhanced SREBP2 expression. On the other hand, CA increased the expression of SHP and lipogenic enzymes such as ACC and SCD-1, but had no effect on SREBP2. The present study demonstrated that colestimide improves hyperglycemia and hyperlipidemia, as well as reducing the hepatic lipid content. In contrast, CA exacerbates hyperlipidemia and increases the hepatic lipid content, although it improves glycemic control. Thus, colestimide is a well-balanced drug for the treatment of diabetes mellitus.

  15. The effect of age and diet on the oral glucose tolerance test in ponies.

    PubMed

    Murphy, D; Reid, S W; Love, S

    1997-11-01

    To evaluate the effects of age and diet on the oral glucose tolerance test (OGTT) in healthy ponies, OGTTs were performed on 2 groups of British native breed ponies (Group A: 7 foals [6-9 months], Group B: 7 mature individuals [6-13 years]) when maintained on either a high fibre pelleted ration only (Groups A and B) or a hay only diet (Group B). Plasma glucose response, following oral glucose administration, for Group A (basal plasma glucose concentration [Glu0] 4.6 +/- 0.4 mmol/l (mean +/- s.d.) increasing to 11.5 +/- 1.3 mmol/l at 90 min) was significantly different (P < 0.05) from that observed for Group B (Glu0 of 4.3 +/- 0.2 mmol/l increasing to 6.8 +/- 1.3 mmol/l at 90 min), when fed the same diet. For Group B ponies, the plasma glucose response, following oral glucose administration, was significantly different (P < 0.05) when fed hay only (Glu0 4.6 +/- 0.4 mmol/l increasing to 9.6 +/- 2.1 mmol/l at 150 min) compared to when fed the high fibre pelleted ration. These results indicate that both age and diet have a significant effect on plasma glucose concentrations measured during an OGTT.

  16. Mice with Deletion of Neuromedin B Receptor Exhibit Decreased Oral Glucose-Stimulated Insulin Release.

    PubMed

    Paula, G S M; Souza, L L; Bressane, N O S; Maravalhas, R; Wilieman, M; Bento-Bernardes, T; Silva, K R; Mendonca, L S; Oliveira, K J; Pazos-Moura, C C

    2016-12-01

    Neuromedin B (NB) and gastrin-releasing peptide (GRP) are bombesin-like peptides, found in the gastrointestinal tube and pancreas, among other tissues. Consistent data proposed that GRP stimulates insulin secretion, acting directly in pancreatic cells or in the release of gastrointestinal hormones that are incretins. However, the role of NB remains unclear. We examined the glucose homeostasis in mice with deletion of NB receptor (NBR-KO). Female NBR-KO exhibited similar fasting basal glucose with lower insulinemia (48.4%) and lower homeostasis model assessment of insulin resistance index (50.5%) than wild type (WT). Additionally, they were more tolerant to oral glucose, demonstrated by a decrease in the area under the glucose curve (18%). In addition, 15 min after an oral glucose load, female and male NBR-KO showed lower insulin serum levels (45.6 and 26.8%, respectively) than WT, even though blood glucose rose to similar levels in both groups. Single injection of NB, one hour before the oral glucose administration, tended to induce higher serum insulin in WT (28.9%, p=0.3), however the same did not occur in NBR-KO. They showed no changes in fasting insulin content in pancreatic islets by immunohistochemistry, however, the fasting serum levels of glucagon-like peptide, a potent incretin, exhibited a strong trend to reduction (40%, p=0.07). Collectively, mice with deletion of NB receptor have lower insulinemia, especially in response to oral glucose, and females also exhibited a better glucose tolerance, suggesting the involvement of NB and its receptor in regulation of insulin secretion induced by incretins, and also, in insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes.

    PubMed

    Robinson, Lindsay E; Savani, Sonali; Battram, Danielle S; McLaren, Drew H; Sathasivam, Premila; Graham, Terry E

    2004-10-01

    Caffeine ingestion negatively affects insulin sensitivity during an oral glucose tolerance test (OGTT) in lean and obese men, but this has not been studied in individuals with type 2 diabetes. We examined the effects of caffeine ingestion on insulin and glucose homeostasis in obese men with type 2 diabetes. Men (n = 12) with type 2 diabetes (age = 49 +/- 2 y, BMI = 32 +/- 1 kg/m(2)) underwent 2 trials, 1 wk apart, in a randomized, double-blind design. Each trial was conducted after withdrawal from caffeine, alcohol, exercise, and oral hypoglycemic agents for 48 h and an overnight fast. Subjects randomly ingested caffeine (5 mg/kg body weight) or placebo capsules and 1 h later began a 3 h 75 g OGTT. Caffeine increased (P < 0.05) serum insulin, proinsulin, and C-peptide concentrations during the OGTT relative to placebo. Insulin area under the curve was 25% greater (P < 0.05) after caffeine than after placebo ingestion. Despite this, blood glucose concentration was also increased (P < 0.01) in the caffeine trial. After caffeine ingestion, blood glucose remained elevated (P < 0.01) at 3 h postglucose load (8.9 +/- 0.7 mmol/L) compared with baseline (6.7 +/- 0.4 mmol/L). The insulin sensitivity index was lower (14%, P = 0.02) after caffeine than after placebo ingestion. Overall, despite elevated and prolonged proinsulin, C-peptide, and insulin responses after caffeine ingestion, blood glucose was also increased, suggesting an acute caffeine-induced impairment in blood glucose management in men with type 2 diabetes.

  18. Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery.

    PubMed

    Bose, Mousumi; Teixeira, Julio; Olivan, Blanca; Bawa, Baani; Arias, Sara; Machineni, Sriram; Pi-Sunyer, F Xavier; Scherer, Philipp E; Laferrère, Blandine

    2010-03-01

    The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short- and long-term changes in hormonal determinants of blood glucose. Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) levels and the incretin effect on insulin secretion. The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP) levels, early phase insulin secretion, and other parameters of β-cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year. The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery.

  19. Glyceollin-containing fermented soybeans improve glucose homeostasis in diabetic mice.

    PubMed

    Park, Sunmin; Kim, Da Sol; Kim, Jeong Hwan; Kim, Jong Sang; Kim, Hyo Jung

    2012-02-01

    Our previous in vitro study demonstrated that glyceollins help normalize glucose homeostasis by potentiating β-cell function and survival in insulinoma cells as well as improving glucose utilization in adipocytes. Here, we investigated whether fermented soybeans containing glyceollins had an antidiabetic action in type 2 diabetic animals. The diabetic mice, their diabetes induced by intraperitoneal injections of streptozotocin (20 mg/kg bw), were administered a high fat diet with no soybeans (control), 10% unfermented soybeans and 10% fermented soybeans containing glyceollins, respectively, (FSG) for 8 weeks. As positive controls, rosiglitazone (20 mg/kg/bw) was given to diabetic mice fed a no soybean diet and non-diabetic mice were also placed on the same diet. Among the diabetic mice, FSG-treated mice exhibited the lowest peak for blood glucose levels with an elevation of serum insulin levels during the first part of oral glucose tolerance testing. FSG also made blood glucose levels drop quickly after the peak and it decreased blood glucose levels more than the control during insulin tolerance testing. This improvement was associated with increased hepatic glycogen accumulation and decreased triglyceride storage. The phosphorylation of Akt, AMP-kinase, and acetyl-CoA carboxylase in the liver was potentiated by FSG, whereas phosphoenolpyruvate carboxykinase expression decreased. The enhancement of glucose homeostasis was comparable to the effect induced by rosiglitazone, a commercial peroxisome proliferator-activated receptor-γ agonist, but it did not match the level of glucose homeostasis in the non-diabetic mice. Glyceollin-containing FSG improves glucose homeostasis, partly by enhancing hepatic insulin sensitivity in type 2 diabetic mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Effect of glycemia on plasma incretins and the incretin effect during oral glucose tolerance test.

    PubMed

    Salehi, Marzieh; Aulinger, Benedict; D'Alessio, David A

    2012-11-01

    The incretin effect, reflecting the enhancement of postprandial insulin secretion by factors including the intestinal hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, increases in proportion to meal size. However, it is unknown whether the incretin effect is dependent on ambient glucose. The goal of this study was to determine the effect of plasma glycemia on the incretin effect. Thirteen healthy subjects consumed 50 g oral glucose solution mixed with d-xylose during fixed hyperglycemia at 8 and 10.5 mmol/L, on 3 separate days, twice at lower glycemia (LOW) and once at higher values (HIGH). The relative increase in insulin release after glucose ingestion at fixed hyperglycemia, a surrogate for the incretin effect, was similar among all three studies. The GLP-1 response to oral glucose was significantly lower at higher plasma glycemia, as was the appearance of d-xylose after the meal. Between the two LOW studies, the reproducibility of insulin release in response to intravenous glucose alone and intravenous plus ingested glucose was similar. These findings indicate that the incretin contribution to postprandial insulin release is independent of glycemia in healthy individuals, despite differences in GLP-1 secretion. The incretin effect is a reproducible trait among humans with normal glucose tolerance.

  1. Factors associated with the glucose-lowering effect of vildagliptin identified from the results of the oral glucose tolerance test in Japanese patients with type 2 diabetes.

    PubMed

    Nakamura, Akinobu; Terauchi, Yasuo

    2013-01-01

    In order to investigate the factors contributing to the glucose-lowering effect of vildagliptin, we analyzed the results of the oral glucose tolerance test together with several clinical parameters in Japanese patients with type 2 diabetes before and after 24 weeks of treatment with vildagliptin. The data of the 13 patients who satisfactorily completed the follow-up examinations were included. After 24 weeks treatment with vildagliptin, the patients were classified into a responder group (69.2%) and a non-responder group (30.8%); the responders consisting of subjects whose HbA1c decreased following 24 weeks treatment with vildagliptin, and the non-responders consisting of subjects who did not show any significant decrease of HbA1c. There were no differences in baseline characteristics between the two groups before administration of vildagliptin. After 24 weeks of treatment, HbA1c was significantly reduced from 7.3 ± 0.5% to 6.7 ± 0.5% in the responder group (P = 0.0077), while it tended to rather increased from 7.1 ± 0.6% to 7.5 ± 0.7% in the non-responder group (P = 0.0679). Also, parameters reflecting the glucose-stimulated insulin secretion, such as the insulinogenic index and oral disposition index, were significantly higher in the responder group than in the non-responder group, whereas insulin sensitivity was similar between the two groups. These results suggest that the difference in the degree of improvement of the glucose tolerance between the responder group and non-responder group in this study could be associated with the effect of vildagliptin on the glucose-stimulated insulin secretion, but not on the insulin sensitivity.

  2. Insulin resistance and lipid profile during an oral glucose tolerance test in women with and without gestational diabetes mellitus.

    PubMed

    Liang, Zx; Wu, Y; Zhu, Xy; Fang, Q; Chen, Dq

    2016-01-01

    We aimed to compare changes in insulin levels during an oral glucose tolerance test (OGTT) between women with normal glucose tolerance (NGT) during pregnancy and those with gestational diabetes mellitus (GDM). Overall, 105 pregnant women between 24 and 28 weeks' gestation, 50 with NGT and 55 with GDM according to NDDG standard, were enrolled into the study. The levels of fasting blood glucose, insulin, triglyceride (TG) and total cholesterol (TC) and the insulin levels, blood glucose levels at 1, 2 and 3 hours post oral glucose administration during an OGTT (5.8, 10.6, 9.2 and 8.1 mmol/L, respectively) were measured. Then, insulin resistance (IR) index was calculated. There was no significant difference in fasting, 3-h insulin levels and 3-h blood glucose levels between those with NGT and those with GDM (P > 0.05). However, 1-h and 2-h insulin levels, fasting and 1-h and 2-h blood glucose levels in women with GDM were significantly higher than those in the NGT group (P < 0.05). Fasting TC and TG levels in the GDM group were significantly higher than those with NGT (P = 0.031 and P = 0.025, respectively). Correlation analysis showed that TG and TC levels were positively correlated with homoeostasis model assessment-IR (HOMA-IR) (r = 0.67 and r = 0.78, respectively; P < 0.05). Our findings suggest that insulin sensitivity in women with GDM was significantly lower than that observed in those with NGT. Reducing IR and blood lipids in women with GDM could potentially improve maternal and foetal outcomes.

  3. Policies for Improving Oral Health in Europe

    ERIC Educational Resources Information Center

    Blinkhorn, Anthony S.; Downer, Martin C.; Drugan, Caroline S.

    2005-01-01

    Background and Objective: The main purpose of this review was to rehearse the available evidence of good practice in dental public health in order to define policies that could improve oral health in the enlarged European Union and associated countries. Secondary objectives were to describe the basic principles of health service organisation and…

  4. Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

    PubMed Central

    Wopereis, Suzan; Rubingh, Carina M.; van Erk, Marjan J.; Verheij, Elwin R.; van Vliet, Trinette; Cnubben, Nicole H. P.; Smilde, Age K.; van der Greef, Jan; van Ommen, Ben; Hendriks, Henk F. J.

    2009-01-01

    Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. Methodology To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. Conclusions Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men. PMID:19242536

  5. Improvement in glycemia after glucose or insulin overload in leptin-infused rats is associated with insulin-related activation of hepatic glucose metabolism.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Frago, Laura M; Chowen, Julie A; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2016-01-01

    Insulin regulates glucose homeostasis through direct effects on the liver, among other organs, with leptin modulating insulin's hepatic actions. Since central leptin may modify insulin signaling in the liver, we hypothesized that leptin infusion activates hepatic glycogen synthesis following peripheral administration of a bolus of glucose or insulin, thus regulating glycemia. Oral glucose and intraperitoneal insulin tolerance tests were performed in control, intracerebroventricular leptin-treated and pair-fed rats during 14 days. An improvement in glycemia and an increase in hepatic free glucose and glycogen concentrations after glucose or insulin overload were observed in leptin-treated rats. In order to analyze whether the liver was involved in these changes, we studied activation of insulin signaling by Western blotting and multiplex bead immunoassay after leptin infusion. Our studies revealed an increase in phosphorylation of insulin receptor substrate-1 and Akt in leptin-treated rats. Examination of parameters related to glucose uptake and metabolism in the liver revealed an augment in glucose transporter 2 and a decrease in phosphoenolpyruvate carboxylase protein levels in this group. These results indicate that central leptin increases hepatic insulin signaling, associated with increased glycogen concentrations after glucose or insulin overload, leading to an improvement in glycemia.

  6. 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

  7. Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats.

    PubMed

    Chukwuma, Chika Ifeanyi; Mopuri, Ramgopal; Nagiah, Savania; Chuturgoon, Anil Amichund; Islam, Md Shahidul

    2017-08-02

    Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3). Experiment 1 examined the effects of increasing concentrations (2.5-20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals. Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals. Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

  8. LX2761, a Sodium/Glucose Cotransporter 1 Inhibitor Restricted to the Intestine, Improves Glycemic Control in Mice.

    PubMed

    Powell, David R; Smith, Melinda G; Doree, Deon D; Harris, Angela L; Greer, Jennifer; DaCosta, Christopher M; Thompson, Andrea; Jeter-Jones, Sabrina; Xiong, Wendy; Carson, Kenneth G; Goodwin, Nicole C; Harrison, Bryce A; Rawlins, David B; Strobel, Eric D; Gopinathan, Suma; Wilson, Alan; Mseeh, Faika; Zambrowicz, Brian; Ding, Zhi-Ming

    2017-07-01

    LX2761 is a potent sodium/glucose cotransporter 1 inhibitor restricted to the intestinal lumen after oral administration. Studies presented here evaluated the effect of orally administered LX2761 on glycemic control in preclinical models. In healthy mice and rats treated with LX2761, blood glucose excursions were lower and plasma total glucagon-like peptide-1 (GLP-1) levels higher after an oral glucose challenge; these decreased glucose excursions persisted even when the glucose challenge occurred 15 hours after LX2761 dosing in ad lib-fed mice. Further, treating mice with LX2761 and the dipeptidyl-peptidase 4 inhibitor sitagliptin synergistically increased active GLP-1 levels, suggesting increased LX2761-mediated release of GLP-1 into the portal circulation. LX2761 also lowered postprandial glucose, fasting glucose, and hemoglobin A1C, and increased plasma total GLP-1, during long-term treatment of mice with either early- or late-onset streptozotocin-diabetes; in the late-onset cohort, LX2761 treatment improved survival. Mice and rats treated with LX2761 occasionally had diarrhea; this dose-dependent side effect decreased in severity and frequency over time, and LX2761 doses were identified that decreased postprandial glucose excursions without causing diarrhea. Further, the frequency of LX2761-associated diarrhea was greatly decreased in mice either by gradual dose escalation or by pretreatment with resistant starch 4, which is slowly digested to glucose in the colon, a process that primes the colon for glucose metabolism by selecting for glucose-fermenting bacterial species. These data suggest that clinical trials are warranted to determine if LX2761 doses and dosing strategies exist that provide improved glycemic control combined with adequate gastrointestinal tolerability in people living with diabetes. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Oral salmon calcitonin improves fasting and postprandial glycemic control in lean healthy rats.

    PubMed

    Feigh, M; Nielsen, R H; Hansen, C; Henriksen, K; Christiansen, C; Karsdal, M A

    2012-02-01

    A novel oral form of salmon calcitonin (sCT) was recently demonstrated to improve both fasting and postprandial glycemic control and induce weight loss in diet-induced obese and insulin-resistant rats. To further explore the glucoregulatory efficacy of oral sCT, irrespective of obesity and metabolic dysfunction, the present study investigated the effect of chronic oral sCT treatment on fasting and postprandial glycemic control in male lean healthy rats. 20 male rats were divided equally into a control group receiving oral vehicle or an oral sCT (2 mg/kg) group. All rats were treated twice daily for 5 weeks. Body weight and food intake were monitored during the study period and fasting blood glucose, plasma insulin and insulin sensitivity were determined and an oral glucose tolerance test (OGTT) performed at study end. Compared with the vehicle group, rats receiving oral sCT had improved fasting glucose homeostasis and insulin resistance, as measured by homeostatic model assessment of insulin resistance index (HOMA-IR), with no change in body weight or fasting plasma insulin. In addition, the rats receiving oral sCT had markedly reduced glycemia and insulinemia during OGTT. This is the first report showing that chronic oral sCT treatment exerts a glucoregulatory action in lean healthy rats, irrespective of influencing body weight. Importantly, oral sCT seems to exert a dual treatment effect by improving fasting and postprandial glycemic control and insulin sensitivity. This and previous studies suggest oral sCT is a promising agent for the treatment of obesity-related insulin resistance and type 2 diabetes.

  10. Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load

    PubMed Central

    Pepino, M. Yanina; Tiemann, Courtney D.; Patterson, Bruce W.; Wice, Burton M.; Klein, Samuel

    2013-01-01

    OBJECTIVE Nonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects. RESEARCH DESIGN AND METHODS Seventeen obese subjects (BMI 42.3 ± 1.6 kg/m2) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (SI), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics. RESULTS Compared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P < 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P < 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose. CONCLUSIONS These data demonstrate that sucralose affects the glycemic and insulin responses to an oral glucose load in obese people who do not normally consume NNS. PMID:23633524

  11. Sucralose affects glycemic and hormonal responses to an oral glucose load.

    PubMed

    Pepino, M Yanina; Tiemann, Courtney D; Patterson, Bruce W; Wice, Burton M; Klein, Samuel

    2013-09-01

    Nonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects. Seventeen obese subjects (BMI 42.3 ± 1.6 kg/m(2)) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤ 2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (SI), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics. Compared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P < 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P < 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose. These data demonstrate that sucralose affects the glycemic and insulin responses to an oral glucose load in obese people who do not normally consume NNS.

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

    PubMed

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

    2015-02-15

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

  13. Predictive ability of fasting plasma glucose for a diabetic 2-h postload glucose value in oral glucose tolerance test: spectrum effect.

    PubMed

    Karakaya, Jale; Aksoy, Duygu Yazgan; Harmanci, Ayla; Karaagaoglu, Ergun; Gurlek, Alper

    2007-01-01

    The performance of diagnostic tests may vary according to patient characteristics. The aim of this study is to find out the factors, if any, that may affect the performance of fasting plasma glucose (FPG) to predict a diabetic 2-h postload glucose level (> or =200 mg/dl) in oral glucose tolerance test (OGTT). One hundred ninety-six patients with known risk factors for diabetes mellitus to whom OGTT was applied were included. Factors that may have an effect on the performance of FPG in prediction of a diabetic value in OGTT were determined by using logistic regression and likelihood ratios (LRs). The cutoff of FPG predicting a 2-h postload glucose of > or =200 mg/dl was calculated by receiver operating characteristic curve as 110 mg/dl (sensitivity, 76.7%; specificity, 75.9%). Waist-to-hip ratio (WHR) and body mass index (BMI) influenced sensitivity, whereas age, family history, and presence of hyperlipidemia affected specificity of FPG. Significant factors for positive LR were age and hyperlipidemia, whereas sex, smoking, hyperlipidemia, physical inactivity, WHR, and BMI influenced negative LR. Fasting plasma glucose performance as a diagnostic test can be affected by many factors that are clearly stated as risk factors for diabetes mellitus. These data emphasize how the interpretation of a diagnostic test varies as the patient characteristics vary; the criteria that we confidently rely on may not be that reliable, changing between just two different patients.

  14. Ceratonia siliqua L. (immature carob bean) inhibits intestinal glucose absorption, improves glucose tolerance and protects against alloxan-induced diabetes in rat.

    PubMed

    Rtibi, Kaïs; Selmi, Slimen; Grami, Dhekra; Saidani, Khouloud; Sebai, Hichem; Amri, Mohamed; Eto, Bruno; Marzouki, Lamjed

    2017-06-01

    This study was designed to investigate the effects of immature carob pod aqueous extract (ICPAE) on intestinal glucose absorption in vitro and in vivo using an oral glucose tolerance test (OGTT) as well as the potential antidiabetic effect in alloxan-induced diabetic rats. OGTT was carried by administration of glucose (2 g kg(-1) , p.o.) and after treatment with extract (50, 100 and 200 mg kg(-1) body weight). Diabetes was induced by single intraperitoneal injection of alloxan (150 mg kg(-1) ). However, the extracts at various doses or glibenclamide (GLB, 10 mg kg(-1) body weight) were given by oral administration for 2 weeks. ICPAE (50-2000 µg mL(-1) ) exerted dose-dependent reduction of sodium-dependent glucose transport across isolated mice jejunum and the maximal inhibition exceeded 50%.The ICPAE treatment improved glucose tolerance. More importantly, ICPAE at various doses showed a significant reduction in blood glucose and biochemical profiles in diabetic rats. Our findings confirm that the degree of maturity of carob characterized by a different phytochemical composition may be responsible for these actions. Therefore, these compounds may be used as a food supplement in hyperglycemia and diabetes treatments. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  15. Comparing glucose and insulin data from the two-hour oral glucose tolerance test in metabolic syndrome subjects and marathon runners.

    PubMed

    Altuve, Miguel; Perpinan, Gilberto; Severeyn, Erika; Wong, Sara

    2016-08-01

    Glucose is the main energy source of the body's cells and is essential for normal metabolism. Two pancreatic hormones, insulin and glucagon, are involved in glucose home-ostasis. Alteration in the plasma glucose and insulin concentrations could lead to distinct symptoms and diseases, ranging from mental function impairment to coma and even death. Type 2 diabetes, insulin resistance and metabolic syndrome are typical examples of abnormal glucose metabolism that increase the risk for cardiovascular disease and mortality. The oral glucose tolerance test (OGTT) is a medical test used to screen for prediabetes, type 2 diabetes and insulin resistance. In the 5-sample 2-hour OGTT, plasma glucose and insulin concentrations are measured after a fast and then after oral intake of glucose, at intervals of 30 minutes. In this work, a statistical analysis is carried out to find significant differences between the five stages of the OGTT for plasma glucose and insulin data. In addition, the behavior of the glucose and insulin data is compared between subjects with the metabolic syndrome and marathon runners. Results show that marathon runners have plasma glucose and insulin levels significantly lower (p <; 0.05) than people with the metabolic syndrome in all the stages of the OGTT. Insulin secretion decreases in marathon runners due to a significant reduction in plasma glucose concentration, but insulin secretion does not decrease in metabolic syndrome subjects due to insulin resistance, consequently plasma glucose concentration does not achieve normal levels.

  16. Postprandial serum C-peptide to plasma glucose concentration ratio correlates with oral glucose tolerance test- and glucose clamp-based disposition indexes.

    PubMed

    Okuno, Yoko; Komada, Hisako; Sakaguchi, Kazuhiko; Nakamura, Tomoaki; Hashimoto, Naoko; Hirota, Yushi; Ogawa, Wataru; Seino, Susumu

    2013-10-01

    The C-peptide index (CPI), a ratio of serum C-peptide to plasma glucose levels, is a readily measured index of β-cell function. The difference in the physiological features reflected by the index measured under fasting (F-CPI) or postprandial (PP-CPI) conditions has remained unclear, however. We investigated the relationship of the two CPIs to indexes of insulin secretion measured with an oral glucose tolerance test (OGTT) or with hyperglycemic and hyperinsulinemic-euglycemic clamp analyses as well as to disposition indexes (indexes of insulin secretion adjusted for insulin sensitivity) calculated from OGTT- or clamp-based analyses. We also examined the relationship between glucose tolerance and the clamp-based disposition index. The clamp-based disposition index declined progressively from normal glucose tolerance to impaired glucose tolerance to Type 2 diabetes, and it strongly correlated with the 2-h plasma glucose level during an OGTT. For patients with Type 2 diabetes, both F-CPI and PP-CPI correlated with indexes of insulin secretion including HOMA-β, the insulinogenic index, the ratio of the area under the insulin curve to that under the glucose curve during an OGTT, the serum C-peptide level after glucagon challenge, as well as early and total insulin secretion measured with a hyperglycemic clamp. PP-CPI, but not F-CPI, was significantly correlated with clamp-based and OGTT-based disposition indexes. F-CPI was correlated only with unadjusted indexes of insulin secretion, whereas PP-CPI was correlated with such indexes as well as with those adjusted for insulin sensitivity. The better clinical utility of PP-CPI might be attributable to these physiological characteristics. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Amino acid mixture acutely improves the glucose tolerance of healthy overweight adults.

    PubMed

    Wang, Bei; Kammer, Lynne M; Ding, Zhenping; Lassiter, David G; Hwang, Jungyun; Nelson, Jeffrey L; Ivy, John L

    2012-01-01

    Certain amino acids have been reported to influence carbohydrate metabolism and blood glucose clearance, as well as improve the glucose tolerance in animal models. We hypothesized that an amino acid mixture consisting of isoleucine and 4 additional amino acids would improve the glucose response of healthy overweight men and women to an oral glucose tolerance test (OGTT). Twenty-two overweight healthy subjects completed 2 OGTTs after consuming 2 different test beverages. The amino acid mixture beverage (CHO/AA) consisted of 0.088 g cystine 2HCl, 0.043 g methionine, 0.086 g valine, 12.094 g isoleucine, 0.084 g leucine, and 100 g dextrose. The control beverage (CHO) consisted of 100 g dextrose only. Venous blood samples were drawn 10 minutes before the start of ingesting the drinks and 15, 30, 60, 120, and 180 minutes after the completion of the drinks. During the OGTT, the plasma glucose response for the CHO/AA treatment was significantly lower than that of the CHO treatment (P < .01), as was the plasma glucose area under the curve (CHO/AA 806 ± 31 mmol/L·3 hours vs CHO 942 ± 40 mmol/L·3 hours). Differences in plasma glucose between treatments occurred at 30, 60, 120, and 180 minutes after supplement ingestion. Plasma glucagon during the CHO/AA treatment was significantly higher than during the CHO treatment. However, there were no significant differences in plasma insulin or C-peptide responses between treatments. These results suggest that the amino acid mixture lowers the glucose response to an OGTT in healthy overweight subjects in an insulin-independent manner.

  18. The role of ranitidine infusion on glucose, insulin and C-peptide serum levels induced by oral glucose tolerance test in healthy subjects.

    PubMed

    Gentile, S; Marmo, R; Costume, A; Orlando, C; D'Alessandro, R; De Bellis, G; Porcellini, M; Coltorti, M

    1986-01-01

    In 9 healthy subjects we evaluated the effect of a constant ranitidine infusion (100 mg) on glucose (mg/dl), insulin (microU/ml) and C-peptide (ng/ml) serum levels promoted by oral glucose tolerance test (75 g). Ranitidine significantly increased the area under concentration/time curves for glucose and insulin but not that of C-peptide. Our data indicate that ranitidine does not affect pancreatic insulin release nor peripheral glucose utilization and are consistent with the hypothesis that ranitidine influences the hepatic clearance of glucose and insulin both of which undergo high first-pass liver extraction.

  19. Improvement in glucose biosensing response of electrochemically grown polypyrrole nanotubes by incorporating crosslinked glucose oxidase.

    PubMed

    Palod, Pragya Agar; Singh, Vipul

    2015-10-01

    In this paper a novel enzymatic glucose biosensor has been reported in which platinum coated alumina membranes (Anodisc™s) have been employed as templates for the growth of polypyrrole (PPy) nanotube arrays using electrochemical polymerization. The PPy nanotube arrays were grown on Anodisc™s of pore diameter 100 nm using potentiostatic electropolymerization. In order to optimize the polymerization time, immobilization of glucose oxidase (GOx) was first performed using physical adsorption followed by measuring its biosensing response which was examined amperometrically for increasing concentrations of glucose. In order to further improve the sensing performance of the biosensor fabricated for optimum polymerization duration, enzyme immobilization was carried out using cross-linking with glutaraldehyde and bovine serum albumin (BSA). Approximately six fold enhancement in the sensitivity was observed in the fabricated electrodes. The biosensors also showed a wide range of linear operation (0.2-13 mM), limit of detection of 50 μM glucose concentration, excellent selectivity for glucose, notable reliability for real sample detection and substantially improved shelf life. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Rise of Oxyntomodulin in Response to Oral Glucose after Gastric Bypass Surgery in Patients with Type 2 Diabetes

    PubMed Central

    Laferrère, Blandine; Swerdlow, Nicholas; Bawa, Baani; Arias, Sara; Bose, Mousumi; Oliván, Blanca; Teixeira, Julio; McGinty, James; Rother, Kristina I.

    2010-01-01

    Context: The mechanisms by which Roux-en-Y gastric bypass surgery (GBP) results in sustained weight loss and remission of type 2 diabetes are not fully understood. Objective: We hypothesized that the anorexic hormone oxyntomodulin (OXM) might contribute to the marked weight reduction and the rapid improvement in glucose metabolism observed in morbidly obese diabetic patients after GBP. Methods: Twenty obese women with type 2 diabetes were studied before and 1 month after GBP (n = 10) or after a diet-induced equivalent weight loss (n = 10). Patients from both groups were matched for age, body weight, body mass index, and diabetes duration and control. OXM concentrations were measured during a 50-g oral glucose challenge before and after weight loss. Results: At baseline, OXM levels (fasting and stimulated values) were indistinguishable between the GBP and the diet group. However, OXM levels rose remarkably in response to an oral glucose load more than 2-fold (peak, 5.25 ± 1.31 to13.8 ± 16.2 pmol/liter; P = 0.025) after GBP but not after diet. The peak of OXM after glucose was significantly correlated with glucagon-like peptide-1 and peptide YY3-36. Conclusions: Our data suggest that the observed changes in OXM primarily occur in response to GBP and not as a consequence of weight loss. These changes were observed early after surgery and occurred in parallel with previously reported increases in incretins and peptide YY. We speculate that the combination of gut hormone changes is essential for the improved glucose homeostasis and may partially explain the success of this surgery on diabetes resolution and weight loss. PMID:20501690

  1. Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients

    PubMed Central

    Handisurya, Ammon; Kerscher, Corinna; Tura, Andrea; Herkner, Harald; Payer, Berit Anna; Mandorfer, Mattias; Werzowa, Johannes; Winnicki, Wolfgang; Reiberger, Thomas; Kautzky-Willer, Alexandra; Pacini, Giovanni; Säemann, Marcus; Schmidt, Alice

    2016-01-01

    Background Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients. Methods In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR). Results After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82–441.92) vs. 468.80 (414.27–488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032–0.106) vs. 0.083 (0.054–0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression. Conclusions HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV

  2. Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients.

    PubMed

    Handisurya, Ammon; Kerscher, Corinna; Tura, Andrea; Herkner, Harald; Payer, Berit Anna; Mandorfer, Mattias; Werzowa, Johannes; Winnicki, Wolfgang; Reiberger, Thomas; Kautzky-Willer, Alexandra; Pacini, Giovanni; Säemann, Marcus; Schmidt, Alice

    2016-01-01

    Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients. In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR). After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression. HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant

  3. Lifestyle intervention according to general recommendations improves glucose tolerance.

    PubMed

    Mensink, Marco; Blaak, Ellen E; Corpeleijn, Eefje; Saris, Wim H; de Bruin, Tjerk W; Feskens, Edith J

    2003-12-01

    Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes. However, it needs to be assessed whether moderate interventions, in agreement with current guidelines for the general population, are effective. We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes. Subjects with glucose intolerance were randomly assigned to either the lifestyle intervention group (INT) or control group (CON). The INT received regular dietary advice and was stimulated to increase their physical activity. The CON received a brief leaflet about healthy diet and increased physical activity. Primary outcome measure was the change in glucose tolerance. In total, 88 subjects completed 2 years of intervention (40 subjects in the INT, 48 subjects in the CON, mean BMI 29.4 kg/m2). Subjects in the INT reduced their body weight, waist circumference, and (saturated) fat intake and improved their aerobic capacity. Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON (p < 0.01). Subjects adherent to both the diet and exercise intervention showed the largest reduction in 2-hour glucose levels. Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance, even in a less obese and more physical active population. Furthermore, our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance.

  4. Oral glucose for pain relief during examination for retinopathy of prematurity: a masked randomized clinical trial

    PubMed Central

    da Costa, Marlene Coelho; Eckert, Gabriela Unchalo; Fortes, Bárbara Gastal Borges; Filho, João Borges Fortes; Silveira, Rita C.; Procianoy, Renato S

    2013-01-01

    OBJECTIVE: Ophthalmologic examination for retinopathy of prematurity is a painful procedure. Pharmacological and non-pharmacological interventions have been proposed to reduce pain during eye examinations. This study aims to evaluate the analgesic effect of 25% glucose using a validated pain scale during the first eye examination for retinopathy of prematurity in preterm infants with birth weight ≤1,500 g and/or gestational age ≤32 weeks. METHODS: A masked, randomized clinical trial for one dose of 1 ml of oral 25% glucose solution 2 minutes before the first ophthalmologic examination for retinopathy of prematurity was conducted between March 2008 and April 2010. The results were compared to those of a control group that did not receive oral glucose solution. Pain was evaluated using a Neonatal Infant Pain Scale immediately before and immediately after the ophthalmologic examination in both groups. Clinicaltrials.gov: NCT00648687 RESULTS: One hundred and twenty-four patients who were examined for the first time for retinopathy of prematurity were included. Seventy were included in the intervention group and 54 in the control group. The number of patients with pain immediately before the procedure was similar in both groups. The number of patients with pain after ophthalmologic examination was 15.7% in the intervention group and 68.5% in the control group (p<0.001). CONCLUSIONS: One ml of oral 25% glucose solution given 2 minutes before an ophthalmologic examination for retinopathy of prematurity was an effective measure for pain relief. PMID:23525316

  5. Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats.

    PubMed

    Feigh, Michael; Andreassen, Kim V; Hjuler, Sara T; Nielsen, Rasmus H; Christiansen, Claus; Henriksen, Kim; Karsdal, Morten A

    2013-07-01

    Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)- and ovariectomy (OVX)-induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored. For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations. For prevention, oral sCT reduced body weight by ∼16% to 19% (P < 0.001), reduced plasma insulin and leptin by ∼50%, and improved impaired fasting glycemia (P < 0.05) concomitantly with amelioration of IR (HOMA-IR; P < 0.01) in HFD- and OVX-induced obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ∼40% and ∼70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P < 0.001). Finally, oral sCT alleviated glucose intolerance predominantly in the portal circulation. Oral sCT treatment displays weight-regulatory and glucoregulatory efficacy in HFD- and OVX-induced obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes.

  6. Factors predictive of macrosomia in pregnancies with a positive oral glucose challenge test: importance of fasting plasma glucose.

    PubMed

    Legardeur, H; Girard, G; Journy, N; Ressencourt, V; Durand-Zaleski, I; Mandelbrot, L

    2014-02-01

    The study aimed to determine the factors associated with fetal macrosomia following a positive oral glucose challenge test (OGCT). In this retrospective single-centre study of 1268 pregnancies with positive 50-g OGCTs (plasma glucose≥130mg/dL, or 7.2mmol/L), gestational diabetes mellitus (GDM) was defined as fasting plasma glucose (FPG)≥95mg/dL (5.3mmol/L) and/or postprandial glucose (PPG)≥120mg/dL (6.7mmol/L). In GDM pregnancies, the odds ratios adjusted for confounders (age, BMI, ethnicity, parity and weight gain) were 2.02 for macrosomia (Z score≥1.28) and 2.62 for severe macrosomia (Z score≥1.88). For each 10-mg/dL increase in FPG, the mean birth-weight increase was 60g. Macrosomia risk did not differ between GDM patients with normal FPG (<95mg/dL, or 5.3mmol/L) and non-diabetics, but increased significantly in cases of FPG≥95mg/dL and regardless of the level of PPG. In our study population, birth-weight and macrosomia risk were strongly correlated with FPG, suggesting that it is a simple and efficient marker for the risk of macrosomia. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Effects of an oral glucose tolerance test on the myogenic response in healthy individuals.

    PubMed

    Lott, Mary E J; Hogeman, Cynthia; Herr, Michael; Gabbay, Robert; Sinoway, Lawrence I

    2007-01-01

    The myogenic response, the inherent ability of blood vessels to rapidly respond to changes in transmural pressure, is involved in local blood flow autoregulation. Animal studies suggest that both acute hyperglycemia and hyperinsulinemia may impair myogenic vasoconstriction. The purpose of this study was to examine the effects of an oral glucose load on brachial mean blood velocity (MBV) during increases in forearm transmural pressure in humans. Eight healthy men and women (38 +/- 5 yr) underwent an oral glucose tolerance test (OGTT). MBV (in cm/s; Doppler ultrasound) responses to a rise in forearm transmural pressure (arm tank suction, -50 mmHg) were studied before and every 30 min for 120 min during the OGTT. Before the start of the OGTT, MBV was lower than baseline values 30 and 60 s after the application of negative pressure. This suggests that myogenic constriction was present. During the OGTT, blood glucose rose from 88 +/- 2 to 120 +/- 6 mg/dl (P < 0.05) and insulin rose from 14 +/- 1 to 101 +/- 32 microU/ml (P < 0.05). Glucose loading attenuated the reduction in MBV with arm suction (Delta-0.73 +/- 0.14 vs. Delta-1.67 +/- 0.43 cm/s and Delta-1.07 +/- 0.14 vs. Delta-2.38 +/- 0.54 cm/s, respectively, during 30 and 60 s of suction postglucose compared with preglucose values; all P < 0.05). We observed no such time effect for myogenic responses during a sham OGTT. In an additional 5 subjects, glucose loading had no effect on brachial diameters with the application of negative pressure. Oral glucose loading leads to attenuated myogenic vasoconstriction in healthy individuals. The role that this diminished postglucose reactivity plays in mediating postprandial hypotension and/or orthostasis needs to be further explored.

  8. Insulin Response to Oral Stimuli and Glucose Effectiveness Increased in Neuroglycopenia Following Roux-en-Y Gastric Bypass

    PubMed Central

    Patti, Mary Elizabeth; Li, Ping; Goldfine, Allison B.

    2015-01-01

    Objective Hyperinsulinemic hypoglycemia with neuroglycopenia is a rare complication following Roux-en-Y gastric bypass (RYGB) surgery for weight management. This study evaluates insulin secretion and action in response to oral and intravenous stimuli in persons with and without neuroglycopenia following RYGB. Design and Methods Cross-sectional cohort studies were performed at a single academic institution to assess insulin secretion and action during oral mixed meal tolerance test (MMTT) and intravenous glucose tolerance test (IVGTT). Results Insulin secretion was increased more following oral mixed meal than intravenous glucose in individuals with neuroglycopenia compared to the asymptomatic group. Reduced insulin clearance did not contribute to higher insulinemia. Glucose effectiveness at zero insulin, estimated during the intravenous glucose tolerance test, was also higher in those with neuroglycopenia. Insulin sensitivity did not differ between groups. Conclusions Increased beta cell response to oral stimuli and insulin-independent glucose disposal may both contribute to severe hypoglycemia after Roux-en-Y gastric bypass. PMID:25755084

  9. [Insulin response and NEFA behavior in volunteers with a flat response to oral glucose tolerance test].

    PubMed

    Viviani, G; Cordera, R; Maiello, M; De Micheli, A; Odetti, P; Corsi, L; Boeri, D; Prando, R

    1979-07-15

    The insulin response and the NEFA behaviour of 7 lean and 8 obese subjects with a flat response to an oral glucose tolerance test have been studied. A flat response has been defined as one in which the maximum glycemic increase and the area of increase does not exceed 32 mg% and 18 mg% respectively. The insulin response and the NEFA behaviour were similar both in lean and in obese subjects to controls with normal O.G.T.T. The glucose/I.R.I. ratios were increased. A possible physiopathological interpretation is proposed.

  10. Deterioration of insulin release rate response to glucose during oral glucose tolerance test is associated with an increased risk of incident diabetes in normal glucose tolerance subjects.

    PubMed

    Li, Yuanyuan; He, Shihui; Sun, Yao; Li, Guangwei; Xu, Qingsong; Wang, Chen; Jia, Weiping

    2017-09-01

    β-Cell dedifferentiation, characterized by loss of glucose sensitivity (β-cell glucose sensitivity [βCGS]), has been reported to play an important role in the development of type 2 diabetes (T2D). Traditionally, βCGS was derived from C-peptide-based method. However, C-peptide was not routinely examined in normal subjects and diabetes never treated with insulin. Thus, the aim of the study was to evaluate the use of insulin in oral glucose tolerance test (OGTT) in estimation of β-cell glucose response ability. A total of 1,599 subjects including normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and T2D were included in the study. A subgroup of NGT subjects (n = 591) were followed up for an average duration of 56.88 ± 20.76 months. Insulin release rate (IRRINS ) in the function of glucose (IRRINS response to glucose [IRRG]) during OGTT was compared with βCGS. Both βCGS derived from C-peptide by deconvolution approach and IRRG by insulin release progressively declined from NGT to IGT and T2D. Both βCGS and IRRG were associated with deposit of first-phase insulin secretion (DI1st ). After 56.88 ± 20.76 months, 32 (5.41%) NGT subjects had developed T2D. NGT subjects who progressed to diabetes after follow-up had lower IRRG and DI1st levels than those who did not (P < 0.01). Furthermore, multiple logistic regression analyses showed that decreased IRRG was a significant independent risk predictor for future diabetes after adjustment of age, body mass index (BMI), homeostasis model assessment (HOMA)-insulin resistance, DI1st and family history. NGT subjects with decreased IRRG during OGTT had defective early insulin secretion and were at higher risk of developing diabetes. IRRG could be a useful T2D predictor in NGT subjects. © 2017 IUBMB Life, 69(9):756-766, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  11. What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia?

    PubMed

    Harris, Deborah L; Gamble, Greg D; Weston, Philip J; Harding, Jane E

    2017-07-11

    To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth. We analyzed data from 227 infants with hypoglycemia (blood glucose <46.8 mg/dL, 2.6 mmol/L) born at a tertiary hospital who experienced 295 episodes of hypoglycemia. Blood glucose concentrations were measured (glucose oxidase) within 90 minutes after randomization to dextrose or placebo gel plus feeding with formula, expressed breast milk, or breast feeding. The overall mean increase in blood glucose concentration was 11.7 mg/dL (95% CI 10.4-12.8). The increase was greater after buccal dextrose gel than after placebo gel (+3.0 mg/dL; 95% CI 0.7-5.3; P = .01) and greater after infant formula than after other feedings (+3.8 mg/dL; 95% CI 0.8-6.7; P = .01). The increase in blood glucose concentration was not affected by breast feeding (+2.0 mg/dL; 95% CI -0.3 to 44.2; P = .09) or expressed breast milk (-1.4 mg/dL; 95% CI -3.7 to 0.9; P = .25). However, breast feeding was associated with reduced requirement for repeat gel treatment (OR = 0.52; 95% CI 0.28-0.94; P = .03). Treatment of infants with hypoglycemia with dextrose gel or formula is associated with increased blood glucose concentration and breast feeding with reduced need for further treatment. Dextrose gel and breast feeding should be considered for first-line oral treatment of infants with hypoglycemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose

    PubMed Central

    Nazarian, Shaban; Peter, John V St; Boston, Raymond C; Jones, Sidney A; Mariash, Cary N

    2011-01-01

    Vitamin D has in vitro and in vivo effects on β-cells and insulin sensitivity. Vitamin D deficiency (VDD) has been associated with onset and progression of type 2 diabetes mellitus (DM-2). However, studies involving supplementation of vitamin D in subjects with previously established diabetes have demonstrated inconsistent effects on insulin sensitivity. The aim of this open-label study was to assess the effects of high dose vitamin D3 supplementation on insulin sensitivity in subjects with VDD and impaired fasting glucose. We studied 8 subjects with VDD and pre-diabetes with the modified frequently sampled intravenous glucose tolerance (mFSIGT) test before and after vitamin D supplementation. Vitamin D3 was administered as 10,000 IU daily for 4 weeks. The mFSIGT was analyzed with MinMod Millennnium to obtain estimates of Acute Insulin Response to Glucose (AIRg), Insulin Sensitivity (SI), and Disposition Index (DI). We found that AIRg decreased (p = 0.011) and insulin sensitivity, expressed as SI, increased (p = 0.012) after a intervention with vitamin D. If these findings are repeated in a randomized, double-blind, sudy the results indicate that orally administered high dose vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose and suggests that high dose vitamin D3 supplementation might provide an inexpensive public health measure in preventing, or at least delaying, the progression from impaired fasting glucose to diabetes. PMID:22005267

  13. Effect of oral protein hydrolysate on glucose control in patients with gestational diabetes.

    PubMed

    Saleh, Langeza; Schrier, Nicole L; Bruins, Maaike J; Steegers, Eric A P; van den Meiracker, Anton H; Visser, Willy

    2017-03-16

    In type 2 diabetic patients, a casein-based protein hydrolysate has been shown to increase plasma insulin and to lower plasma glucose. In the present study, we examined the acute and prolonged effects of protein hydrolysate on postprandial glucose, insulin and C-peptide responses after a standardised breakfast and the effect on daily glucose control in patients with gestational diabetes. In a single-centre randomised double blind placebo controlled design, patients with mild gestational diabetes (no use of insulin or oral antidiabetic agents; n = 26/group) were allocated to receive a protein hydrolysate drink, 8.5 g before breakfast and 8.5 g before dinner or a placebo drink which was identical to the protein hydrolysate drink in appearance and taste, yet lacked carbohydrate, fat or protein, for 8 days. Baseline characteristics including fasting levels of glucose, insulin, C-peptide and insulin-glucose ratio were similar between the groups. Compared to the placebo drink, neither the first dose of the protein hydrolysate drink nor the final dose had effects on 4-h area under the curve for plasma levels of insulin and C-peptide, or the insulin-to-glucose ratio; however, plasma glucose was moderately lower between t = 45, 60 and 75 min. In addition, mean daily capillary glucose levels were lower in the protein hydrolysate group. Two patients in the PH drink group had to be withdrawn because of vomiting after the first dose. In patients with gestational diabetes, a twice-daily dose of 8.5 g of protein hydrolysate of casein had no insulinotropic effects, but did moderately reduce plasma glucose levels, suggesting an increase in insulin sensitivity. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  14. Relationships of Early And Late Glycemic Responses With Gastric Emptying During An Oral Glucose Tolerance Test.

    PubMed

    Marathe, Chinmay S; Horowitz, Michael; Trahair, Laurence G; Wishart, Judith M; Bound, Michelle; Lange, Kylie; Rayner, Christopher K; Jones, Karen L

    2015-09-01

    The early glycemic response during a 75-g oral glucose tolerance test (OGTT) is directly related to the rate of gastric emptying (GE). There is little information about the effect of GE on the blood glucose at either 60 min (a predictor of diabetes) or 120 min (used diagnostically). This study aimed to evaluate the relationships between glycemic responses at 30, 60, and 120 min and GE following a 75-g OGTT in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2D). Eighty-two subjects in the general community without diabetes (57 NGT, 25 IGT) and 16 with T2D consumed a 75-g glucose drink labeled with (99m)Tc-sulfur colloid. GE (by scintigraphy) and glycemia were measured from t = 0-120 min and relationships between blood glucose (absolute, change from baseline, and area under the curve) and GE at 30, 60, and 120 min determined. There were no differences in GE. There were relationships between the blood glucose at 30 min and GE (NGT: r = 0.40; P < .01; IGT: r = 0.49; P = .02; T2D: r = 0.62; P = .01). There was also a relationship between the blood glucose at 60 min and GE in IGT (r = 0.52; P = .02) and T2D (r = 0.77; P < .01), but not NGT (r = 0.16; P = .24). In NGT, there was an inverse relationship between blood glucose at 120 min and GE (r = -0.30; P = .02), but not in IGT (r = 0.05; P = .82) or T2D (r = 0.37; P = .16). GE is a determinant of the glycemic response to an OGTT in NGT, IGT, and T2D but these relationships differ and are time dependent.

  15. SGLT1 sugar transporter/sensor is required for post-oral glucose appetition.

    PubMed

    Sclafani, Anthony; Koepsell, Hermann; Ackroff, Karen

    2016-04-01

    Recent findings suggest that the intestinal sodium-glucose transporter 1 (SGLT1) glucose transporter and sensor mediates, in part, the appetite-stimulation actions of intragastric (IG) glucose and nonmetabolizable α-methyl-d-glucopyranoside (MDG) infusions in mice. Here, we investigated the role of SGLT1 in sugar conditioning using SGLT1 knockout (KO) and C57BL/6J wild-type (WT) mice. An initial experiment revealed that both KO and WT mice maintained on a very low-carbohydrate diet display normal preferences for saccharin, which was used in the flavored conditioned stimulus (CS) solutions. In experiment 2, mice were trained to drink one flavored solution (CS+) paired with an IG MDG infusion and a different flavored solution (CS-) paired with IG water infusion. In contrast to WT mice, KO mice decreased rather than increased the intake of the CS+ during training and failed to prefer the CS+ over the CS- in a choice test. In experiment 3, the KO mice also decreased their intake of a CS+ paired with IG glucose and avoided the CS+ in a choice test, unlike WT mice, which preferred the CS+ to CS-. In experiment 4, KO mice, like WT mice preferred a glucose + saccharin solution to a saccharin solution. These findings support the involvement of SGLT1 in post-oral glucose and MDG conditioning. The results also indicate that sugar malabsorption in KO mice has inhibitory effects on sugar intake but does not block their natural preference for sweet taste.

  16. SGLT1 sugar transporter/sensor is required for post-oral glucose appetition

    PubMed Central

    Koepsell, Hermann

    2016-01-01

    Recent findings suggest that the intestinal sodium-glucose transporter 1 (SGLT1) glucose transporter and sensor mediates, in part, the appetite-stimulation actions of intragastric (IG) glucose and nonmetabolizable α-methyl-d-glucopyranoside (MDG) infusions in mice. Here, we investigated the role of SGLT1 in sugar conditioning using SGLT1 knockout (KO) and C57BL/6J wild-type (WT) mice. An initial experiment revealed that both KO and WT mice maintained on a very low-carbohydrate diet display normal preferences for saccharin, which was used in the flavored conditioned stimulus (CS) solutions. In experiment 2, mice were trained to drink one flavored solution (CS+) paired with an IG MDG infusion and a different flavored solution (CS−) paired with IG water infusion. In contrast to WT mice, KO mice decreased rather than increased the intake of the CS+ during training and failed to prefer the CS+ over the CS− in a choice test. In experiment 3, the KO mice also decreased their intake of a CS+ paired with IG glucose and avoided the CS+ in a choice test, unlike WT mice, which preferred the CS+ to CS−. In experiment 4, KO mice, like WT mice preferred a glucose + saccharin solution to a saccharin solution. These findings support the involvement of SGLT1 in post-oral glucose and MDG conditioning. The results also indicate that sugar malabsorption in KO mice has inhibitory effects on sugar intake but does not block their natural preference for sweet taste. PMID:26791832

  17. The effect of low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test.

    PubMed

    Kamau, R K; Maina, F W; Kigondu, C; Mati, J K

    1990-08-01

    The effect of a low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test was studied in 29, 30 and 9 indigenous Kenyan women respectively. Glucose tolerance test was performed before treatment was started and then after 1,3 and 6 months in microgynon users. The mean areas under the glucose curves were also significantly elevated. Significant increase in blood glucose values were noted only at 30 minutes after 6 months of use of the progestogen-only oral contraceptive but the mean blood glucose values were higher than in the control after 1,3 and 6 months of use. However, the mean values of the areas under the glucose curves were significantly elevated after 1,3, and 6 months of use. Medroxyprogesterone acetate users showed significantly lower fasting blood glucose values at 60 and 90 minutes after 1 month of use, after which the blood glucose values returned to the pre-treatment values. The mean values of the glucose curve areas showed no significant change. It is concluded that both microgynon and minipill cause relative impairment of glucose tolerance test as early as after 1 month of use. Medroxyprogesterone acetate does not impair oral glucose tolerance for at least the first 6 months of use. The implications of these findings are discussed.

  18. The oral glucose tolerance test is frequently abnormal in patients with uncontrolled epilepsy.

    PubMed

    Vianna, J B M; Atallah, A N; Prado, G F; Valente, O; Duarte-Barros, M L; Vianna, E C S; Mello, L E A M

    2006-08-01

    The clinical efficacy of the ketogenic diet as therapy for patients with difficult-to-treat epilepsy prompted us to investigate the glucose metabolism of these patients under an oral overload of glucose, that is, in the oral glucose tolerance test (OGTT). Thirty patients (12 males, 18 females; age range: 17-59, mean: 35.1) with difficult-to-treat epilepsy, 23 patients with controlled epilepsy (11 males, 12 females; age range: 14-66, mean: 36.9), and 39 control subjects (18 males, 21 females; age range: 16-58, mean: 33.3) were evaluated with the OGTT. For patients with epilepsy, we also measured C-peptide and glycosylated hemoglobin in the fasting state. Glucose levels lower than 70 mg/dL at any point of the curve were considered to be abnormal. All subjects in the control group and the group with controlled epilepsy had a normal OGTT. In contrast, all 30 patients with difficult-to-treat epilepsy had at least one point on the OGTT curve below the normal range (P<0.001), most often 180 and 240 minutes after the oral glucose load (P<0.001). C-peptide levels were significantly lower in the group with difficult-to-treat epilepsy as compared with the group with controlled epilepsy. Fasting glycohemoglobin and insulin levels did not differ between the two patient groups. We suggest that undiagnosed metabolic disturbances in patients with difficult-to-treat epilepsy may somehow contribute to their refractoriness to conventional pharmacological therapy. We propose the hypothesis that calorie-restricted diets aimed at correcting OGTT curves may prove beneficial in treating patients with difficult-to-treat epilepsy. Our hypothesis generates a clear endpoint for the diet, and its demonstration would provide new standards for diet-based antiepileptic regimens. Accordingly, our results may help in understanding the positive consequences of ketogenic or calorie-restricted diets in persons with seizures.

  19. 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

  20. Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus.

    PubMed

    Ozeki, Noriyuki; Hara, Kenji; Yatsuka, Chikako; Nakano, Tomoki; Matsumoto, Sachiko; Suetsugu, Mariko; Nakamachi, Takafumi; Takebayashi, Kohzo; Inukai, Toshihiko; Haruki, Kohsuke; Aso, Yoshimasa

    2009-10-01

    Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 +/- 0.15 at baseline to 0.43 +/- 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (DeltaI(0-30)/DeltaG(0-30)) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = -0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in

  1. Ghrelin and leptin response to oral glucose challenge among antipsychotic drug-treated children.

    PubMed

    Winsberg, Bertrand; Usubiaga, Helen; Cooper, Tom

    2007-12-01

    We investigated ghrelin, leptin, glucose, and insulin response to an oral glucose tolerance test among children receiving antipsychotics. Hormone concentrations were assayed at fasting, 30, 60, and 120 minutes. The sample was composed of 9 obese (defined as at or above the 95th percentile for age) and 10 overweight/normal children (defined as less than the 95th percentile in weight) based on National Institutes of Health criteria. Ages of the obese (10.7 +/- 3.4 years) and the overweight/normal (13.1 +/- 1.6 years) did not differ. Leptin was significantly higher among the obese group and did not change consequent to glucose. Ghrelin did not differ between the groups, and when the values were combined, ghrelin decreased at 30 minutes and approached fasting concentrations at 120 minutes. To further explore our data, we constituted separate groups based upon z score changes. When weight gain defined as an increase in z score (X = 0.4), the nongainers showed leptin concentrations to decrease over time. Findings encourage further oral glucose tolerance test studies to explain the leptin response to weight gain seen among children receiving antipsychotic medication.

  2. Modification of corporal weight, body fat distribution, blood lipids and glucose levels in oral contraceptive users.

    PubMed

    Carranza-Lira, S; Bueno Fontal, J P

    2000-01-01

    The association between oral contraceptives and the modification of corporal weight and body fat distribution is controversial. The characteristics of the menstrual cycle, lipids and glucose levels were also analyzed. Thirty women who received ethinylestradiol 0.035 mg and norethindrone 0.400 mg for one year were studied. The following variables were analyzed every 3 months: weight, body mass index (BMI), hip perimeter, waist perimeter, waist-hip ratio (WHR), duration of menstrual cycle, quantity of uterine bleeding, as well as blood levels of cholesterol, triglycerides and glucose. Waist and hip perimeters increased during the third evaluation; as well as the BMI starting from the second evaluation. The triglycerides levels rose from the first evaluation. No modifications were found in the WHR, glucose and cholesterol levels and the duration of the menstrual cycle, but the quantity of uterine bleeding decreased from the third month. The oral contraceptive significantly increased BMI and triglycerides level, but no changes were detected in body fat distribution, cholesterol and glucose levels. Uterine bleeding decreased from the first evaluation.

  3. Feeding and oral glucose--additive effects on pain reduction in newborns.

    PubMed

    Gradin, Maria; Finnström, Orvar; Schollin, Jens

    2004-04-01

    The aims of this study were to compare the pain reducing effect of oral glucose with that of being breast-fed shortly before venipuncture in newborns, and also the pain score and crying time with parents' assessment. Randomised, controlled trial. 120 full term newborns undergoing venipuncture randomly assigned to on of four groups: I, Breast-fed and 1-ml placebo; II, Breast-fed and 1-ml 30% glucose; III, Fasting and 1-ml placebo; and IV, Fasting and 1-ml 30% glucose. Pain during venipuncture was measured with the Premature Infant Pain Profile (PIPP). Crying time was recorded. The parents assessed their babies' pain on a Visual Analogue Scale (VAS). The PIPP score was significantly lower in the infants receiving glucose, than in those not given glucose (p=0.004). There was no significant difference in PIPP score between the infants who were fed and the fasting infants. The PIPP score was lower in group II (median 7) than in group I (md 10). There was a similar difference between group IV (md 9) and group III (md 11). The median crying times during the first 3 min in groups I, II, III, and IV were 63, 18, 142 and 93 s, respectively. There was low agreement between the parents' assessment of pain and the PIPP score and crying time. Breast-feeding shortly before venipuncture has no major impact on the pain score but on crying time. The combination of oral glucose and breast-feeding shows the lowest pain score and significantly shorter duration of crying.

  4. Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at?

    PubMed

    Zhao, Xinjie; Peter, Andreas; Fritsche, Jens; Elcnerova, Michaela; Fritsche, Andreas; Häring, Hans-Ulrich; Schleicher, Erwin D; Xu, Guowang; Lehmann, Rainer

    2009-02-01

    The oral glucose tolerance test (oGTT) is a common tool to provoke a metabolic challenge for scientific purposes, as well as for diagnostic reasons, to monitor the kinetics of glucose and insulin. Here, we aimed to follow the variety of physiological changes of the whole metabolic pattern in plasma during an oGTT in healthy subjects in a nontargeted reversed-phase ultra performance liquid chromatography coupled to electrospray ionization quadrupole time of flight mass spectrometric metabolomics approach. We detected 11,500 metabolite ion masses/individual. Applying multivariate data analysis, four major groups of metabolites have been detected as the most discriminating oGTT biomarkers: free fatty acids (FFA), acylcarnitines, bile acids, and lysophosphatidylcholines. We found in detail 1) a strong decrease of all saturated and monounsaturated FFA studied during the oGTT; 2) a significant faster decline of palmitoleate (C16:1) and oleate (C18:1) FFA levels than their saturated counterparts; 3) a strong relative increase of polyunsaturated fatty acids in the fatty acid pattern at 120 min; and 4) a clear decrease in plasma C10:0, C12:0, and C14:1 acylcarnitine levels. These data reflect the switch from beta-oxidation to glycolysis and fat storage during the oGTT. Moreover, the bile acids glycocholic acid, glycochenodeoxycholic acid, and glycodeoxycholic acid were highly discriminative, showing a biphasic kinetic with a maximum of a 4.5- to 6-fold increase at 30 min after glucose ingestion, a significant decrease over the next 60 min followed by an increase until the end of the oGTT. Lysophosphatidylcholines were also increased significantly. The findings of our metabolomics study reveal detailed insights in the complex physiological regulation of the metabolism during an oGTT offering novel perspectives of this widely used procedure.

  5. Immunohistochemical Evaluation of Glucose Transporter Type 1 in Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

    PubMed

    Pereira, Karuza Maria Alves; Feitosa, Sthefane Gomes; Lima, Ana Thayssa Tomaz; Luna, Ealber Carvalho Macedo; Cavalcante, Roberta Barroso; de Lima, Kenio Costa; Chaves, Filipe Nobre; Costa, Fábio Wildson Gurgel

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and some of these have been documented in association or preceded by oral epithelial dysplasia (OED). Aggressive cancers with fast growth have demonstrated overexpression of some glucose transporters (GLUTs). Thus, the aim of this study was to analyze the immunohistochemical expression of the glucose transporter, GLUT-1, in OEDs and OSCCs, seeking to better elucidate the biological behavior of neoplasias. Fifteen cases were selected this research of both lesions. Five areas were analyzed from each case by counting the percentage of positive cells at 400x magnification. Immunoreactivity of GLUT-1 was observed in 100% of the samples ranging from 54.2% to 86.2% for the OSCC and 73.9% to 97.4% for the OED. Statistical test revealed that there was greater overexpression of GLUT-1 in OED than the OSCC (p=0.01). It is believed the high expression of GLUT-1 may reflect the involvement of GLUT-1 in early stages of oral carcinogenesis.

  6. Improved Glucose Homeostasis in Obese Mice Treated With Resveratrol Is Associated With Alterations in the Gut Microbiome.

    PubMed

    Sung, Miranda M; Kim, Ty T; Denou, Emmanuel; Soltys, Carrie-Lynn M; Hamza, Shereen M; Byrne, Nikole J; Masson, Grant; Park, Heekuk; Wishart, David S; Madsen, Karen L; Schertzer, Jonathan D; Dyck, Jason R B

    2017-02-01

    Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and an increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transplantation from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol. © 2017 by the American Diabetes Association.

  7. Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight.

    PubMed

    Sisley, Stephanie R; Arble, Deanna M; Chambers, Adam P; Gutierrez-Aguilar, Ruth; He, Yanlin; Xu, Yong; Gardner, David; Moore, David D; Seeley, Randy J; Sandoval, Darleen A

    2016-09-01

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei. © 2016 by the American Diabetes Association.

  8. Is There a Threshold Oral Glucose Tolerance Test Value for Predicting Adverse Pregnancy Outcome?

    PubMed

    Stuebe, Alison M; Landon, Mark B; Lai, Yinglei; Klebanoff, Mark; Ramin, Susan M; Wapner, Ronald J; Varner, Michael W; Rouse, Dwight J; Sciscione, Anthony; Catalano, Patrick; Saade, George; Sorokin, Yoram; Peaceman, Alan M

    2015-07-01

    This study aims to determine whether there is a threshold 3-hour oral glucose tolerance test (OGTT) value associated with accelerated risk of adverse pregnancy outcomes. In a secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, we used generalized additive models with smoothing splines to explore nonlinear associations between each of the 3-hour OGTT values (fasting, 1-hour, 2-hour, and 3-hour) and adverse pregnancy outcomes, including the study's composite outcome (perinatal mortality, hypoglycemia, hyperbilirubinemia, neonatal hyperinsulinemia, and/or birth trauma), large for gestational age birth weight, small for gestational age birth weight, shoulder dystocia, neonatal hypoglycemia, gestational hypertension (gHTN), and preeclampsia. Among the 1,360 eligible women, each timed OGTT value was linearly associated with increased odds of composite adverse outcome. We found evidence of a departure from linearity only for the association between fasting glucose and gHTN/preeclampsia, with a stronger association for values of 85 to 94 mg/dL (p = 0.03). We found no evidence of departure from linearity for any other OGTT values and measured outcomes (all chi-square test p-values ≥ 0.05). In a population of untreated women with mild gestational glucose intolerance and fasting OGTT < 95 mg/dL, we found an increasing risk of gHTN with a fasting glucose between 85 and 94 mg/dL. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents.

    PubMed

    Yeckel, Catherine W; Weiss, Ram; Dziura, James; Taksali, Sara E; Dufour, Sylvie; Burgert, Tania S; Tamborlane, William V; Caprio, Sonia

    2004-03-01

    Given the extreme increase in prediabetes, type 2 diabetes, and the potential for metabolic syndrome in obese youth, identifying simplified indexes for assessing stimulated insulin sensitivity is critical. The purpose of this study was validation of two surrogate indexes of insulin sensitivity determined from the oral glucose tolerance test (OGTT): the composite whole body insulin sensitivity index (WBISI) and the insulin sensitivity index (ISI). An obese population (aged 8-18 yr) of normal and impaired glucose tolerance individuals was studied. One group (n = 38) performed both the euglycemic-hyperinsulinemic clamp and OGTT for comparison of insulin sensitivity measurements as well as (1)H-magnetic resonance spectroscopy estimates of intramyocellular lipid content. Another larger (n = 368) cohort participated only in an OGTT. Both the WBISI and ISI represented good estimates (r = 0.78 and 0.74; P < 0.0005) for clamp-derived insulin sensitivity (glucose disposed, M-value), respectively. In the large cohort, the surrogate indexes demonstrated the shift toward poorer function and increased risk profile as a function of insulin resistance. Additionally, the WBISI and ISI correlated with intramyocellular lipid content (r = -0.74 and -0.71; P < 0.0001), a tissue marker for insulin resistance. Insulin sensitivity can be estimated using plasma glucose and insulin responses derived from the OGTT in obese youth with normal and impaired glucose tolerance.

  10. Improving Oral Reports: A Heuristic Approach.

    ERIC Educational Resources Information Center

    Glossner, Alan J.

    A student's fear of giving oral reports and the instructor's objection to using too much class time on oral reports are often seen as the major barriers that prevent an oral communication unit from being included in a business or management communications course. One approach to easing both concerns is the use of videotaping as a self-discovery…

  11. Single Fasting Plasma Glucose Versus 75-g Oral Glucose-Tolerance Test in Prediction of Adverse Perinatal Outcomes: A Cohort Study.

    PubMed

    Shen, Songying; Lu, Jinhua; Zhang, Lifang; He, Jianrong; Li, Weidong; Chen, Niannian; Wen, Xingxuan; Xiao, Wanqing; Yuan, Mingyang; Qiu, Lan; Cheng, Kar Keung; Xia, Huimin; Mol, Ben Willem J; Qiu, Xiu

    2017-02-01

    There remains uncertainty regarding whether a single fasting glucose measurement is sufficient to predict risk of adverse perinatal outcomes. We included 12,594 pregnant women who underwent a 75-g oral glucose-tolerance test (OGTT) at 22-28weeks' gestation in the Born in Guangzhou Cohort Study, China. Outcomes were large for gestational age (LGA) baby, cesarean section, and spontaneous preterm birth. We calculated the area under the receiver operator characteristic curves (AUCs) to assess the capacity of OGTT glucose values to predict adverse outcomes, and compared the AUCs of different components of OGTT. 1325 women had a LGA baby (10.5%). Glucose measurements were linearly associated with LGA, with strongest associations for fasting glucose (odds ratio 1.37, 95% confidence interval 1.30-1.45). Weaker associations were observed for cesarean section and spontaneous preterm birth. Fasting glucose have a comparable discriminative power for prediction of LGA to the combination of fasting, 1h, and 2h glucose values during OGTT (AUCs, 0.611 vs. 0.614, P=0.166). The LGA risk was consistently increased in women with abnormal fasting glucose (≥5.1mmol/l), irrespective of 1h or 2h glucose levels. A single fasting glucose measurement performs comparably to 75-g OGTT in predicting risk of having a LGA baby. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Lack of effect of tenoxicam on dynamic responses to concurrent oral doses of glucose and glibenclamide.

    PubMed Central

    Hartmann, D; Korn, A; Komjati, M; Heinz, G; Haefelfinger, P; Defoin, R; Waldhäusl, W K

    1990-01-01

    1. In a single-blind, placebo controlled study the influence of tenoxicam on responses of glucose, insulin and C-peptide to oral doses of glucose and glibenclamide was examined in 16 healthy male volunteers. 2. The subjects received once daily doses of 2.5 mg glibenclamide for 12 days. From day 5 through 12 eight subjects received concomitantly 20 mg tenoxicam once daily and the remaining eight subjects received placebo. 3. On days 1, 4, 5 and 12 glibenclamide was taken with 75 g glucose and blood glucose, serum insulin and C-peptide were measured over 5 h. Plasma levels of glibenclamide and tenoxicam (where appropriate) were followed over 10 h. 4. Characteristic parameters of blood glucose and insulin and C-peptide responses did not change significantly with time (day) and there was no difference between both treatment groups. 5. Baseline insulin increased from 11.7 mu l-1 on day 1 to 15.6 mu l-1 on day 4 (P = 0.009), likewise baseline C-peptide increased from 478 pmol l-1 to 530 pmol l-1 (P = 0.05), but there was no further change in the subsequent treatment period. 6. The AUC of the glibenclamide plasma concentration-time curve did not show changes with time or differences between treatment groups. The mean (s.d.) oral clearance of tenoxicam was 2.5 (1.5) ml min-1 and appeared slightly higher than in previous studies. 7. It was concluded that tenoxicam did not affect overall glycoregulation in healthy subjects under glibenclamide steady state conditions. PMID:2119677

  13. Flavor change and food deprivation are not critical for post-oral glucose appetition in mice.

    PubMed

    Ackroff, Karen; Sclafani, Anthony

    2015-03-01

    When mice trained to consume a CS- flavored solution paired with intragastric (IG) water self-infusion are given a new CS+ flavor paired with IG glucose self-infusion, their intake is stimulated within minutes in the first CS+ test. They also display a preference for the CS+ over the CS- in two-bottle tests. These indicators of post-oral appetite stimulation (appetition) have been studied in food-restricted mice, with novel CS+ and CS- flavors. Two experiments tested whether deprivation and flavor novelty are needed for stimulation of intake. Exp. 1 compared food-restricted and ad libitum fed C57BL/6 mice trained for 1h/day: 3 sessions with CS- flavor and IG water followed by 3 sessions with a novel CS+ flavor and IG 16% glucose. Ad libitum (AL) fed mice licked less overall, but like the food-restricted (FR) group they increased licking in the first session. In the choice test, FR mice displayed a significant CS+ preference (73%) whereas AL mice had a weaker preference (64%). In Exp. 2, food-restricted mice were trained with a flavor and IG water, and then the Same or a New flavor paired with IG 8% glucose. The glucose infusion rapidly stimulated intakes in the first and subsequent sessions and to the same degree in the two groups. Both groups also showed similar reductions in licking in extinction tests with IG water infusions. These data show that mice need not be explicitly food deprived or given a novel flavor cue to increase ongoing ingestion in response to post-oral glucose stimulation.

  14. Glucose-fructose likely improves gastrointestinal comfort and endurance running performance relative to glucose-only.

    PubMed

    Wilson, P B; Ingraham, S J

    2015-12-01

    This study aimed to determine whether glucose-fructose (GF) ingestion, relative to glucose-only, would alter performance, metabolism, gastrointestinal (GI) symptoms, and psychological affect during prolonged running. On two occasions, 20 runners (14 men) completed a 120-min submaximal run followed by a 4-mile time trial (TT). Participants consumed glucose-only (G) or GF (1.2:1 ratio) beverages, which supplied ∼ 1.3 g/min of carbohydrate. Substrate use, blood lactate, psychological affect [Feeling Scale (FS)], and GI distress were measured. Differences between conditions were assessed using magnitude-based inferential statistics. Participants completed the TT 1.9% (-1.9; -4.2, 0.4) faster with GF, representing a likely benefit. FS ratings were possibly higher and GI symptoms were possibly-to-likely lower with GF during the submaximal period and TT. Effect sizes for GI distress and FS ratings were relatively small (Cohen's d = ∼0.2 to 0.4). GF resulted in possibly higher fat oxidation during the submaximal period. No clear differences in lactate were observed. In conclusion, GF ingestion - compared with glucose-only - likely improves TT performance after 2 h of submaximal running, and GI distress and psychological affect are likely mechanisms. These results apply to runners consuming fluid at 500-600 mL/h and carbohydrate at 1.0-1.3 g/min during running at 60-70% VO2peak . © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Delphinidin-Rich Maqui Berry Extract (Delphinol®) Lowers Fasting and Postprandial Glycemia and Insulinemia in Prediabetic Individuals during Oral Glucose Tolerance Tests

    PubMed Central

    Alvarado, Jorge L.; Salgado, Ana-María; Lyon, Carolina; Vigil, Pilar

    2016-01-01

    Delphinidin anthocyanins have previously been associated with the inhibition of glucose absorption. Blood glucose lowering effects have been ascribed to maqui berry (Aristotelia chilensis) extracts in humans after boiled rice consumption. In this study, we aimed to explore whether a standardized delphinidin-rich extract from maqui berry (Delphinol) affects glucose metabolism in prediabetic humans based on glycemia and insulinemia curves obtained from an oral glucose tolerance test (OGTT) after a challenge with pure glucose. Volunteers underwent four consecutive OGTTs with at least one week washout period, in which different doses of Delphinol were administered one hour before glucose intake. Delphinol significantly and dose-dependently lowered basal glycemia and insulinemia. Lower doses delayed postprandial glycemic and insulinemic peaks, while higher doses reversed this tendency. Glycemia peaks were dose-dependently lowered, while insulinemia peaks were higher for the lowest dose and lower for other doses. The total glucose available in blood was unaffected by treatments, while the total insulin availability was increased by low doses and decreased by the highest dose. Taken together, these open exploratory results suggest that Delphinol could be acting through three possible mechanisms: by inhibition of intestinal glucose transporters, by an incretin-mediated effect, or by improving insulin sensitivity. PMID:28025651

  16. Plasma glucose and insulin response to two oral nutrition supplements in adults with type 2 diabetes mellitus

    PubMed Central

    Huhmann, Maureen B; Smith, Kristen N; Schwartz, Sherwyn L; Haller, Stacie K; Irvin, Sarah; Cohen, Sarah S

    2016-01-01

    Objective The purpose of this clinical trial was to compare the glucose usage of two oral nutritional supplement (ONS) products and to assess whether a diabetes-specific formulation provides improved glucose stabilization and management compared with a standard formula. Research design and methods A total of 12 subjects with type 2 diabetes (7 males and 5 females) completed a randomized, cross-over design trial. Each subject consumed isocaloric amounts of either the standard ONS or the diabetes-specific formula ONS on different dates, 1 week apart. Glucose and insulin measures were recorded at baseline, and 10, 20, 30, 60, 90, 120, 150, 180, 210 and 240 min after the beverage was consumed and then used to calculate area under the curve (AUC) for each subject. Results The mean glucose AUC was lower in the diabetes-specific ONS group than in the standard group (p<0.0001), but there was not a significant difference observed for mean insulin AUC (p=0.068). A sensitivity analysis of the mean insulin AUC measures was performed by removing a potential outlier from the analysis, and this resulted in a significant difference between the groups (p=0.012). First-phase insulin measures and an insulinogenic index calculated for the beverages showed no significant differences. Conclusions On the basis of the results of this trial of 12 subjects, the diabetes-specific ONS appears to provide better glucose maintenance in persons with type 2 diabetes when compared to the standard formula ONS. Trial registration number NCT02612675. PMID:27648290

  17. Decrease of serum S100B during an oral glucose tolerance test correlates inversely with the insulin response.

    PubMed

    Steiner, Johann; Bernstein, Hans-Gert; Schiltz, Kolja; Haase, Thekla; Meyer-Lotz, Gabriela; Dobrowolny, Henrik; Müller, Ulf J; Martins-de-Souza, Daniel; Borucki, Katrin; Schroeter, Matthias L; Isermann, Berend; Bogerts, Bernhard; Westphal, Sabine

    2014-01-01

    Increased S100B serum levels have been considered as a marker of glial pathology, brain damage, and blood-brain-barrier impairment. However, S100B expression has also been detected outside the nervous system, suggesting that altered S100B serum levels may not exclusively reflect brain-specific pathologies. Notably, S100B secretion in adipocytes seems to be down-regulated by insulin, and up-regulated by stress and fasting. Therefore, we assumed that dynamic changes of S100B could be observed by challenging healthy subjects with an oral glucose tolerance test (OGTT). OGTT was performed in 17 healthy adult test persons (9 male and 8 female). Apart from S100B, glucose, free fatty acids, insulin, C-peptide, and cortisol were determined in all samples after an overnight fast (0 h), as well as 1h and 2h after ingestion of 75 g glucose. Mean S100B concentrations decreased about 20% during the first hour after glucose ingestion (P<0.001). This decrease of S100B levels was not related to the declining morning peak of cortisol. However, the decrease of serum-S100B 1h after glucose ingestion correlated inversely with the respective changes of serum-insulin (r = -0.484, P=0.049) and serum-C-peptide (r = -0.570, P = 0.017). Our study suggests an inverse correlation between insulin secretion and S100B release after a standardized OGTT. Additional experiments, including the administration of insulin and the measurement of other food intake-related factors are important to ascertain an insulin-regulated S100B release in vivo. To improve comparability between clinical studies assessing conditions with rather mild changes of serum S100B, blood should be taken in a more standardized way (e.g., after fasting overnight).

  18. An oral lipid challenge and acute intake of caffeinated coffee additively decrease glucose tolerance in healthy men.

    PubMed

    Beaudoin, Marie-Soleil; Robinson, Lindsay E; Graham, Terry E

    2011-04-01

    Lipid-induced insulin resistance has been investigated primarily with i.v. infusions, and caffeine-induced insulin resistance, with alkaloid caffeine. The effects of orally consumed lipids and coffee have not been established and to our knowledge have never been simultaneously investigated. The goals of this study were to determine whether an oral lipid challenge and caffeinated coffee would disrupt glucose homeostasis and to characterize their respective incretin responses. It was hypothesized that oral ingestion of saturated lipids would impair glucose tolerance and that caffeinated coffee would further hinder glucose management. Ten young, healthy males participated in 5 trials in a randomized, cross-over design. At time 0 h, they underwent an oral fat tolerance test (OFTT: 1 g lipid/kg body weight) or consumed water, followed 5 h later by caffeinated (5 mg/kg) coffee, decaffeinated coffee, or water. At 6 h, volunteers underwent an oral glucose tolerance test (OGTT). Consumption of the OFTT increased glucose concentrations (P < 0.05) after a subsequent OGTT. At 7 h, caffeinated coffee produced the highest glucose concentrations (P < 0.05). Glucagon-like peptide-1 active (GLP-1a) and glucose-dependent insulinotropic polypeptide (GIP) were both increased for up to 6 h in all OFTT trials (P < 0.05). Compared to all other treatments, caffeinated and decaffeinated coffee produced higher GLP-1a response at 6.25 h (P < 0.05), whereas only caffeinated coffee increased GIP secretion (P < 0.05). These results show that oral consumption of lipids and caffeinated coffee can independently and additively decrease glucose tolerance. Incretin hormones could explain at least in part this impaired glucose homeostasis.

  19. Nitrogenous compounds stimulate glucose-derived acid production by oral Streptococcus and Actinomyces.

    PubMed

    Norimatsu, Yuka; Kawashima, Junko; Takano-Yamamoto, Teruko; Takahashi, Nobuhiro

    2015-09-01

    Both Streptococcus and Actinomyces can produce acids from dietary sugars and are frequently found in caries lesions. In the oral cavity, nitrogenous compounds, such as peptides and amino acids, are provided continuously by saliva and crevicular gingival fluid. Given that these bacteria can also utilize nitrogen compounds for their growth, it was hypothesized that nitrogenous compounds may influence their acid production; however, no previous studies have examined this topic. Therefore, the present study aimed to assess the effects of nitrogenous compounds (tryptone and glutamate) on glucose-derived acid production by Streptococcus and Actinomyces. Acid production was evaluated using a pH-stat method under anaerobic conditions, whereas the amounts of metabolic end-products were quantified using high performance liquid chromatography. Tryptone enhanced glucose-derived acid production by up to 2.68-fold, whereas glutamate enhanced Streptococcus species only. However, neither tryptone nor glutamate altered the end-product profiles, indicating that the nitrogenous compounds stimulate the whole metabolic pathways involving in acid production from glucose, but are not actively metabolized, nor do they alter metabolic pathways. These results suggest that nitrogenous compounds in the oral cavity promote acid production by Streptococcus and Actinomyces in vivo.

  20. Electrolyte vs. glucose-electrolyte isotonic solutions for oral rehydration therapy in horses.

    PubMed

    Monreal, L; Garzón, N; Espada, Y; Ruíz-Gopegui, R; Homedes, J

    1999-07-01

    An isotonic electrolyte solution with a composition similar to equine sweat was compared to an isotonic glucose-glycine-electrolyte solution for oral rehydration therapy in exercising horses. Ten horses were dehydrated by using frusemide and allocated randomly to receive 4 different oral solutions: isotonic sweat-like electrolyte solution, half-strength hypotonic electrolyte solution, isotonic glucose-glycine-electrolyte solution, and plain water. Solutions were given by nasogastric tube using the same volume as the bodyweight lost by each horse. Blood samples were collected before and throughout 6 h of the rehydration period. Results showed that all solutions recovered pre-frusemide values of packed cell volume (PCV) and total plasma protein (TP) in a similar fashion. No changes for Na+ values were observed during the rehydration period when the isotonic sweat-like solution was used. However, a significant hyponatraemia was induced throughout rehydration when the other 3 solutions were given, especially when hypotonic solution and water were used. Osmolality values did not change when both isotonic solutions were administered; but a significant hypotonicity was observed when hypotonic solution and water were given. When the isotonic sweat-like solution was used, plasma Cl-, K+ and creatinine values recovered to premedication values significantly faster than the other 3 solutions. In conclusion, the isotonic sweat-like electrolyte was the best solution because it restored rapidly the fluid and plasma electrolyte imbalances. In contrast, the isotonic glucose-glycine-electrolyte solution impaired the plasma electrolyte imbalances.

  1. Improving Oral Cancer Survival: The Role of Dental Providers

    PubMed Central

    MESSADI, DIANA V.; WILDER-SMITH, PETRA; WOLINSKY, LAWRENCE

    2010-01-01

    Oral cancer accounts for 2 percent to 4 percent of all cancers diagnosed each year in the United States. In contrast to other cancers, the overall U.S. survival rate from oral cancer has not improved during the past 50 years, mostly due to late-stage diagnosis. Several noninvasive oral cancer detection techniques that emerged in the past decade will be discussed, with a brief overview of most common oral cancer chemopreventive agents. PMID:19998655

  2. β-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose Tolerance After Vertical Sleeve Gastrectomy.

    PubMed

    Garibay, Darline; McGavigan, Anne K; Lee, Seon A; Ficorilli, James V; Cox, Amy L; Michael, M Dodson; Sloop, Kyle W; Cummings, Bethany P

    2016-09-01

    Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes remission; however, the mechanisms responsible for this remain incompletely defined. Glucagon-like peptide-1 (GLP-1) is a gut hormone that contributes to the maintenance of glucose homeostasis and is elevated after VSG. VSG-induced increases in postprandial GLP-1 secretion have been proposed to contribute to the glucoregulatory benefits of VSG; however, previous work has been equivocal. In order to test the contribution of enhanced β-cell GLP-1 receptor (GLP-1R) signaling we used a β-cell-specific tamoxifen-inducible GLP-1R knockout mouse model. Male β-cell-specific Glp-1r(β-cell+/+) wild type (WT) and Glp-1r(β-cell-/-) knockout (KO) littermates were placed on a high-fat diet for 6 weeks and then switched to high-fat diet supplemented with tamoxifen for the rest of the study. Mice underwent sham or VSG surgery after 2 weeks of tamoxifen diet and were fed ad libitum postoperatively. Mice underwent oral glucose tolerance testing at 3 weeks and were euthanized at 6 weeks after surgery. VSG reduced body weight and food intake independent of genotype. However, glucose tolerance was only improved in VSG WT compared with sham WT, whereas VSG KO had impaired glucose tolerance relative to VSG WT. Augmentation of glucose-stimulated insulin secretion during the oral glucose tolerance test was blunted in VSG KO compared with VSG WT. Therefore, our data suggest that enhanced β-cell GLP-1R signaling contributes to improved glucose regulation after VSG by promoting increased glucose-stimulated insulin secretion.

  3. Improved Oxygen-Beam Texturing of Glucose-Monitoring Optics

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A.

    2006-01-01

    An improved method has been devised for using directed, hyperthermal beams of oxygen atoms and ions to impart desired textures to the tips of polymethylmethacrylate [PMMA] optical fibers to be used in monitoring the glucose content of blood. The improved method incorporates, but goes beyond, the method described in Texturing Blood-Glucose- Monitoring Optics Using Oxygen Beams (LEW-17642-1), NASA Tech Briefs, Vol. 29, No. 4 (April 2005), page 11a. The basic principle of operation of such a glucose-monitoring sensor is as follows: The textured surface of the optical fiber is coated with chemicals that interact with glucose in such a manner as to change the reflectance of the surface. Light is sent down the optical fiber and is reflected from, the textured surface. The resulting change in reflectance of the light is measured as an indication of the concentration of glucose. The required texture on the ends of the optical fibers is a landscape of microscopic cones or pillars having high aspect ratios (microscopic structures being taller than they are wide). The average distance between hills must be no more than about 5 mso that blood cells (which are wider) cannot enter the valleys between the hills, where they would interfere with optical sensing of glucose in the blood plasma. On the other hand, the plasma is required to enter the valleys, and high aspect ratio structures are needed to maximize the surface area in contact with the plasma, thereby making it possible to obtain a given level of optical glucose-measurement sensitivity with a relatively small volume of blood. There is an additional requirement that the hills be wide enough that a sufficient amount of light can propagate into them and, after reflection, can propagate out of them. The method described in the cited prior article produces a texture comprising cones and pillars that conform to the average-distance and aspect-ratio requirements. However, a significant fraction of the cones and pillars are so

  4. A new route to improved glucose yields in cellulose hydrolysis

    SciTech Connect

    Zhao, Haibo; Holladay, John E.; Kwak, Ja Hun; Zhang, Z. Conrad

    2007-08-01

    An unusual inverse temperature-dependent pathway was discovered for cellulose decrystallization in trifluoroacetic acid (TFA). Cellulose was completely decrystallized by TFA at 0 °C in less than 2 hours, a result not achieved in 48 hours at 25°C in the same medium. The majority of TFA used in cellulose decrystallization was recycled via a vacuum process. The small remaining amount of TFA was diluted with water to make a 0.5% TFA solution and used as a catalyst in dilute acid hydrolysis. After one minute, under batch conditions at 185 °C, the glucose yield reached 63.5% without production of levulinic acid. In comparison, only 15.0% glucose yield was achieved in the hydrolysis of untreated cellulose by 0.5% H2SO4 under the same condition. Further improvement of glucose yield is possible by optimizing reaction conditions. Alternatively, the remaining TFA can be completely removed by water while keeping the regenerated cellulose in a highly amorphous state. This regenerated cellulose is much more reactive than untreated cellulose in hydrolysis reactions, but still less reactive than corn starch. The lower temperatures and shorter reaction times with this activated cellulose makes it possible to reduce operating costs and decrease byproduct yields such as HMF and levulinic acid.

  5. Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

    SciTech Connect

    Kang, Seong-Il; Jin, Young-Jun; Ko, Hee-Chul; Choi, Soo-Youn; Hwang, Joon-Ho; Whang, Ilson; Kim, Moo-Han; Shin, Hye-Sun; Jeong, Hyung-Bok; Kim, Se-Jae

    2008-08-22

    The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPAR{gamma} luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.

  6. Mycoprotein reduces glycemia and insulinemia when taken with an oral-glucose-tolerance test.

    PubMed

    Turnbull, W H; Ward, T

    1995-01-01

    This study investigated the effects of mycoprotein, a food produced by the continuous fermentation of Fusarium graminearum (Schwabe), on acute glycemia and insulinemia in normal healthy individuals. Subjects participated in two single-meal study periods in a crossover design. After an overnight fast, subjects were given milkshakes containing mycoprotein or a control substance, which were isoenergetic and nutrient balanced. Each milkshake contained 75 g carbohydrate, equivalent to a standard World Health Organization oral-glucose-tolerance test. Blood samples were taken fasting and at 30, 60, 90, and 120 min postprandially for the measurement of serum glucose and insulin. Glycemia was reduced postmeal after mycoprotein compared with the control and was statistically significant at 60 min (13% reduction). Insulinemia was reduced postmeal after mycoprotein compared with the control and was statistically significant at 30 min (19% reduction) and 60 min (36% reduction) postmeal. These results may be significant in the dietary treatment of diabetes.

  7. Caloric restriction and L-carnitine administration improves insulin sensitivity in patients with impaired glucose metabolism.

    PubMed

    Molfino, Alessio; Cascino, Antonia; Conte, Caterina; Ramaccini, Cesarina; Rossi Fanelli, Filippo; Laviano, Alessandro

    2010-01-01

    Reduced circulating and tissue carnitine levels, possibly leading to impaired mitochondrial function, have been postulated to be involved in the pathogenesis of insulin resistance. However, whether L-carnitine administration may improve insulin sensitivity in patients with impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM-2) is still controversial. The aim of the study was to explore the role of L-carnitine supplementation in influencing insulin sensitivity. A randomized controlled study involving adult outpatients was designed. Adult patients referred to the outpatient clinic and within 10 days of the diagnosis of IFG or DM-2 were consecutively enrolled. Exclusion criteria were concomitant antidiabetic therapy and modifications of lifestyle during the previous 4 weeks. Patients were randomly assigned to receive a hypocaloric diet for 10 days (group C; n = 8) or the same dietetic regimen in addition to oral L-carnitine (2 g twice daily) supplementation (group LC; n = 8). Oral glucose tolerance test (OGTT), fasting plasma insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at the beginning and end of the study. Data were statistically analyzed using the Student t test for paired and unpaired data. OGTT at 2 hours improved in both groups. Only in the L-carnitine-supplemented group did plasma insulin levels and HOMA-IR significantly decrease when compared to baseline values. Considering the role of caloric restriction in increasing the intestinal uptake of carnitine, the results suggest that oral L-carnitine administration, when associated with a hypocaloric feeding regimen, improves insulin resistance and may represent an adjunctive treatment for IFG and DM-2.

  8. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice.

    PubMed

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-06-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice.

  9. Noninvasive blood glucose monitoring during oral intake of different sugars with optical coherence tomography in human subjects.

    PubMed

    Zhang, Yuqing; Wei, Huajiang; Yang, Hongqin; He, Yonghong; Wu, Guoyong; Xie, Shusen; Zhu, Zhenguo; He, Ruoyu

    2013-09-01

    The potential of OCT applied to noninvasive blood glucose monitoring has attracted significant efforts. In this work we investigated the feasibility of OCT in monitoring blood glucose during oral intake of different sugars in humans. Five groups of experiments were performed, in which different sugars were used. The OCT signal slope (OCTSS) changed with variation of blood glucose concentration (BGC). A good correlation between OCTSS and BGC was observed in these experiments. The averaged correlation coefficients R between OCTSS and BGC are 0.900, 0.836, 0.895 and 0.884, corresponding to oral administration of glucose, fructose, sucrose and mixed sugar, respectively. Our studies demonstrated the capability and accuracy of the OCT system in monitoring BGC noninvasively and it could become a powerful tool in daily blood glucose monitoring for patients. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.

    PubMed

    Sartori, Claudio; Dessen, Pierre; Mathieu, Caroline; Monney, Anita; Bloch, Jonathan; Nicod, Pascal; Scherrer, Urs; Duplain, Hervé

    2009-12-01

    Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.

  11. Restoring HSP70 deficiencies improves glucose tolerance in diabetic monkeys

    PubMed Central

    Flynn, David M.; Jenkins, Kurt A.; Zhang, Li; Wagner, Janice D.

    2011-01-01

    We evaluated heat shock protein 70 (HSP70) changes in diabetes mellitus (DM) in a nonhuman primate model. To this end, two studies were conducted in DM vervet monkeys. 1) Normal control and streptozotocin-induced DM monkeys (Stz-DM) that were differentiated into moderately or poorly controlled DM by judicious insulin administration were evaluated. Liver was collected at 4, 8, 12, 16, and 20 wk after streptozotocin, exposed to ex vivo heat shock at 42°C, and immunoblotted for heat shock factor 1 (HSF1), HSP70, and phosphorylated HSF1. 2) Spontaneous DM monkeys that were not pharmacologically induced were included in a crossover study of the HSP70-inducing drug geranylgeranylacetone (GGA). GGA at 20 mg/kg was given for 14 days with a 6-wk washout period. Glucose tolerance testing and plasma and muscle HSP70 were the primary outcome measurements. In Stz-DM, hyperglycemia reduced hepatic HSP70 in a dose-dependent fashion. HSF1 was increased in livers of monkeys with Stz-DM, but responses to ex vivo heat shock were impaired vs. normal monkeys. Activation of HSF1 appears to be important, because the phosphorylation change with heat stress was nearly perfectly correlated with HSP70 increases. Impaired HSF1 activation was also seen in Stz-DM after chronic hyperglycemia (>12 wk). In naturally occurring DM, increased circulating HSP70 resulted in significantly improved glucose tolerance and significant, positive trends in other measurements of insulin resistance. No change in muscle HSP70 content was observed. We conclude that increasing HSP70, potentially through targeting hyperglycemia-related deficits in HSF1 induction and activation in the liver, is a potent and viable strategy to improve glucose tolerance. PMID:21325107

  12. 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

  13. Therapeutic vaccine against DPP4 improves glucose metabolism in mice.

    PubMed

    Pang, Zhengda; Nakagami, Hironori; Osako, Mariana K; Koriyama, Hiroshi; Nakagami, Futoshi; Tomioka, Hideki; Shimamura, Munehisa; Kurinami, Hitomi; Takami, Yoichi; Morishita, Ryuichi; Rakugi, Hiromi

    2014-04-01

    The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed a dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention and treatment of type 2 diabetes mellitus. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased DPP4 titer, inhibited plasma DPP4 activity, and induced an increase in the plasma glucagon-like peptide 1 level. Moreover, this elevated titer was sustained for 3 mo. In mice fed a high-fat diet, DPP4 vaccination resulted in improved postprandial glucose excursions and insulin sensitivity and, in the diabetic KK-A(y) and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both plasma insulin and pancreatic insulin content. Importantly, T cells were not activated following challenge with DPP4 itself, which suggests that this vaccine does not induce cell-mediated autoimmunity. Additionally, no significant immune-mediated damage was detected in cells and tissues where DPP4 is expressed. Thus, this DPP4 vaccine may provide a therapeutic alternative for patients with diabetes.

  14. Effects of sitagliptin and metformin treatment on incretin hormone and insulin secretory responses to oral and "isoglycemic" intravenous glucose.

    PubMed

    Vardarli, Irfan; Arndt, Elisabeth; Deacon, Carolyn F; Holst, Jens J; Nauck, Michael A

    2014-02-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent degradation of incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]), whereas metformin may increase GLP-1 levels. We examined, in a four-period crossover trial, the influence of metformin (2,000 mg/day), sitagliptin (100 mg/day), or their combination, on GLP-1 responses and on the incretin effect in 20 patients with type 2 diabetes, comparing an oral glucose challenge (75 g, day 5) and an "isoglycemic" intravenous glucose infusion (day 6). Fasting total GLP-1 was significantly increased by metformin and not changed by sitagliptin. After oral glucose, metformin increased and sitagliptin significantly decreased (by 53%) total GLP-1. Fasting and postload intact GLP-1 increased with sitagliptin but not with metformin. After oral glucose, only sitagliptin, but not metformin, significantly augmented insulin secretion, in monotherapy and as an add-on to metformin. The incretin effect was not changed numerically with any of the treatments. In conclusion, sitagliptin increased intact GLP-1 and GIP through DPP-4 inhibition but reduced total GLP-1 and GIP (feedback inhibition) without affecting the numerical contribution of the incretin effect. Insulin secretion with sitagliptin treatment was similarly stimulated with oral and "isoglycemic" intravenous glucose. This points to an important contribution of small changes in incretin concentrations within the basal range or to additional insulinotropic agents besides GLP mediating the antidiabetic effects of DPP-4 inhibition.

  15. Amantadine reduces glucagon and enhances insulin secretion throughout the oral glucose tolerance test: central plus peripheral nervous system mechanisms

    PubMed Central

    Lechin, Fuad; van der Dijs, Bertha; Pardey-Maldonado, Betty; Rivera, Jairo E; Lechin, Marcel E; Baez, Scarlet

    2009-01-01

    Objective The purpose of the trial was to examine the effects of amantadine, a N-methyl-D-aspartate (NMDA) antagonist, on the oral glucose tolerance test (OGTT) plus insulin, glucagon and neurotransmitters circulating levels. Previous findings showed that hyperinsulinism and type 2 diabetes are positively associated with neural sympathetic and adrenal sympathetic activities, respectively. These peripheral sympathetic branches depend on the pontine (A5-noradrenergic) and the rostral ventrolateral (C1-adrenergic) medullary nuclei. They are excited by glutamate axons which act at NMDA postsynaptic receptors. Research design and methods One OGTT plus placebo and one OGTT plus oral amantadine test were carried out two weeks apart in 15 caucasic normal voluntary humans. Noradrenaline, adrenaline, dopamine, plasma-free serotonin, platelet serotonin, glucose, glucagon, and insulin were measured throughout the 180-minute testing period. Results Maximal reductions of plasma glucose and glucagon plus exacerbated insulin rises were significantly greater throughout the oral glucose plus amantadine test than those registered throughout the oral glucose plus placebo challenge. The above findings were paralleled by greater than normal noradrenaline/adrenaline plasma ratio increases. In addition, maximal reductions of the platelet serotonin and plasma serotonin circulating values contrasted with the normal rises of these parameters, always registered during the glucose load plus placebo challenge. Conclusion This study supports the theory that amantadine might be a powerful antidiabetic tool and could be added to the therapeutic arsenal against type 2 diabetes. PMID:21437134

  16. Helichrysum and grapefruit extracts inhibit carbohydrate digestion and absorption, improving postprandial glucose levels and hyperinsulinemia in rats.

    PubMed

    de la Garza, Ana Laura; Etxeberria, Usune; Lostao, María Pilar; San Román, Belén; Barrenetxe, Jaione; Martínez, J Alfredo; Milagro, Fermín I

    2013-12-11

    Several plant extracts rich in flavonoids have been reported to improve hyperglycemia by inhibiting digestive enzyme activities and SGLT1-mediated glucose uptake. In this study, helichrysum ( Helichrysum italicum ) and grapefruit ( Citrus × paradisi ) extracts inhibited in vitro enzyme activities. The helichrysum extract showed higher inhibitory activity of α-glucosidase (IC50 = 0.19 mg/mL) than α-amylase (IC50 = 0.83 mg/mL), whereas the grapefruit extract presented similar α-amylase and α-glucosidase inhibitory activities (IC50 = 0.42 mg/mL and IC50 = 0.41 mg/mL, respectively). Both extracts reduced maltose digestion in noneverted intestinal sacs (57% with helichrysum and 46% with grapefruit). Likewise, both extracts inhibited SGLT1-mediated methylglucoside uptake in Caco-2 cells in the presence of Na(+) (56% of inhibition with helichrysum and 54% with grapefruit). In vivo studies demonstrated that helichrysum decreased blood glucose levels after an oral maltose tolerance test (OMTT), and both extracts reduced postprandial glucose levels after the oral starch tolerance test (OSTT). Finally, both extracts improved hyperinsulinemia (31% with helichrysum and 50% with grapefruit) and HOMA index (47% with helichrysum and 54% with grapefruit) in a dietary model of insulin resistance in rats. In summary, helichrysum and grapefruit extracts improve postprandial glycemic control in rats, possibly by inhibiting α-glucosidase and α-amylase enzyme activities and decreasing SGLT1-mediated glucose uptake.

  17. Improving quality and efficiency in oral hygiene.

    PubMed

    Meckstroth, R L

    1989-06-01

    A large percentage of the residents in long-term care facilities are unable to achieve an acceptable level of oral hygiene due to mental and physical incapacities and must thus rely on nursing staff for daily oral care. Significant morbidity is associated with chronic inadequate oral hygiene. In addition, a lack of self-esteem related to poor dental status has been observed in some nursing home patients, leading to withdrawal from social interaction and personal isolation. The Collis Curve toothbrush removed more plaque than the straight bristle toothbrush. The curved bristle toothbrush was well received by the residents and well accepted by the nursing staff. A clinically significant number of staff reported that the curved bristle toothbrush made their job easier. Monitoring of the nurses' aides' brushing techniques during the study caused them to provide more effective oral hygiene than prior to the study. The importance of proper oral hygiene must be monitored and supported by nursing supervisors, regardless of the type of brush, used to achieve acceptable levels of oral hygiene.

  18. Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle

    PubMed Central

    2014-01-01

    Background Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain. Methods C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro. Results Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle. Conclusions Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders. PMID:25114710

  19. Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle.

    PubMed

    Tsutsumi, Rie; Yoshida, Tomomi; Nii, Yoshitaka; Okahisa, Naoki; Iwata, Shinya; Tsukayama, Masao; Hashimoto, Rei; Taniguchi, Yasuko; Sakaue, Hiroshi; Hosaka, Toshio; Shuto, Emi; Sakai, Tohru

    2014-01-01

    Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain. C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro. Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle. Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders.

  20. Prevalence of diabetes in Catalonia (Spain): an oral glucose tolerance test-based population study.

    PubMed

    Castell, C; Tresserras, R; Serra, J; Goday, A; Lloveras, G; Salleras, L

    1999-01-01

    The goal of this study was to investigate the prevalence of diabetes mellitus and impaired glucose tolerance in the adult population of Catalonia and study their association with obesity, central obesity, hypertension and smoking habit. A random sample of 3839 subjects aged 30-89 years participated in this cross-sectional study: 2214 subjects underwent a health examination with oral glucose tolerance test (OGTT) and 1625 were interviewed by phone. Diabetes prevalence (known and unknown) in the 30-89-year-old population was 10.3%, (95% CI: 9.1-11.6). In this age group, the prevalence rates of known diabetes, unknown diabetes and impaired glucose tolerance were 6.4, 3.9 and 11.9% in men and 6.9, 3.4 and 11.9% in women. The age adjusted prevalence to the world population for the 30-64-year-old age group was 6.1% (7.1% in men and 5.2% in women).The factors significantly associated with diabetes were age, obesity, hypertension and family history of diabetes. The high ratio of previously known diabetic cases to newly discovered ones, specially in the oldest age group, suggests good levels of awareness and medical services. The prevalence in Catalonia is similar to that observed in other Mediterranean countries.

  1. Evaluation of suppression of growth hormone levels following a 75g oral glucose tolerance test.

    PubMed

    Nazaimoon, W M; Ng, M L; Satgunasingam, N; Khalid, B A

    1992-06-01

    Growth hormone (GH) levels were measured after a 75g oral glucose load (OGTT) in normal adults, patients with impaired glucose tolerance (IGT), insulin-dependent diabetes mellitus (IDDM) and acromegaly. Nadir GH levels at 2-hour post-OGTT in normal subjects ranged from 0.4 to 8.4 mIU/L, the 95% confidence interval being 0.4-4.4 mIU/L. In IGT and IDDM subjects basal fasting GH levels were not significantly different from normal and did not alter during OGTT. The high fasting GH level measured in one each of the IGT and IDDM patients was suppressible at 1-hour after glucose intake. In contrast, acromegalic patients had elevated fasting GH levels (11.8-178 mIU/L) although in 3 patients, the levels were mildly elevated and overlapped with normal. OGTT failed or only partially suppressed GH secretion in all acromegalics. Therefore, elevated fasting GH levels are not diagnostic and OGTT is required for accurate diagnosis and assessment of treatment of acromegalic patients.

  2. Impaired Increase of Plasma Abscisic Acid in Response to Oral Glucose Load in Type 2 Diabetes and in Gestational Diabetes

    PubMed Central

    Ameri, Pietro; Bruzzone, Santina; Mannino, Elena; Sociali, Giovanna; Andraghetti, Gabriella; Salis, Annalisa; Ponta, Monica Laura; Briatore, Lucia; Adami, Giovanni F.; Ferraiolo, Antonella; Venturini, Pier Luigi; Maggi, Davide; Cordera, Renzo; Murialdo, Giovanni; Zocchi, Elena

    2015-01-01

    The plant hormone abscisic acid (ABA) is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT) human subjects, plasma ABA (ABAp) increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D) subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i) 9 treatment-naive T2D subjects, and ii) 9 pregnant women with gestational diabetes (GDM), who underwent the glucose load before and 8–12 weeks after childbirth. Each group was compared with matched NGT controls. The increase of ABAp in response to glucose was found to be abrogated in T2D patients compared to NGT controls. A similar result was observed in the women with GDM compared to pregnant NGT controls; 8–12 weeks after childbirth, however, fasting ABAp and ABAp response to glucose were restored to normal in the GDM subjects, along with glucose tolerance. We also retrospectively compared fasting ABAp before and after bilio-pancreatic diversion (BPD) in obese, but not diabetic subjects, and in obese T2D patients, in which BPD resulted in the resolution of diabetes. Compared to pre-BPD values, basal ABAp significantly increased 1 month after BPD in T2D as well as in NGT subjects, in parallel with a reduction of fasting plasma glucose. These results indicate an impaired hyperglycemia-induced ABAp increase in T2D and in GDM and suggest a beneficial effect of elevated ABAp on glycemic control. PMID:25723556

  3. Impaired increase of plasma abscisic Acid in response to oral glucose load in type 2 diabetes and in gestational diabetes.

    PubMed

    Ameri, Pietro; Bruzzone, Santina; Mannino, Elena; Sociali, Giovanna; Andraghetti, Gabriella; Salis, Annalisa; Ponta, Monica Laura; Briatore, Lucia; Adami, Giovanni F; Ferraiolo, Antonella; Venturini, Pier Luigi; Maggi, Davide; Cordera, Renzo; Murialdo, Giovanni; Zocchi, Elena

    2015-01-01

    The plant hormone abscisic acid (ABA) is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT) human subjects, plasma ABA (ABAp) increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D) subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i) 9 treatment-naive T2D subjects, and ii) 9 pregnant women with gestational diabetes (GDM), who underwent the glucose load before and 8-12 weeks after childbirth. Each group was compared with matched NGT controls. The increase of ABAp in response to glucose was found to be abrogated in T2D patients compared to NGT controls. A similar result was observed in the women with GDM compared to pregnant NGT controls; 8-12 weeks after childbirth, however, fasting ABAp and ABAp response to glucose were restored to normal in the GDM subjects, along with glucose tolerance. We also retrospectively compared fasting ABAp before and after bilio-pancreatic diversion (BPD) in obese, but not diabetic subjects, and in obese T2D patients, in which BPD resulted in the resolution of diabetes. Compared to pre-BPD values, basal ABAp significantly increased 1 month after BPD in T2D as well as in NGT subjects, in parallel with a reduction of fasting plasma glucose. These results indicate an impaired hyperglycemia-induced ABAp increase in T2D and in GDM and suggest a beneficial effect of elevated ABAp on glycemic control.

  4. Sugarcane transgenics expressing MYB transcription factors show improved glucose release.

    PubMed

    Poovaiah, Charleson R; Bewg, William P; Lan, Wu; Ralph, John; Coleman, Heather D

    2016-01-01

    Sugarcane, a tropical C4 perennial crop, is capable of producing 30-100 tons or more of biomass per hectare annually. The lignocellulosic residue remaining after sugar extraction is currently underutilized and can provide a significant source of biomass for the production of second-generation bioethanol. MYB31 and MYB42 were cloned from maize and expressed in sugarcane with and without the UTR sequences. The cloned sequences were 98 and 99 % identical to the published nucleotide sequences. The inclusion of the UTR sequences did not affect any of the parameters tested. There was little difference in plant height and the number of internodes of the MYB-overexpressing sugarcane plants when compared with controls. MYB transgene expression determined by qPCR exhibited continued expression in young and maturing internodes. MYB31 downregulated more genes within the lignin biosynthetic pathway than MYB42. MYB31 and MYB42 expression resulted in decreased lignin content in some lines. All MYB42 plants further analyzed showed significant increases in glucose release by enzymatic hydrolysis in 72 h, whereas only two MYB31 plants released more glucose than control plants. This correlated directly with a significant decrease in acid-insoluble lignin. Soluble sucrose content of the MYB42 transgenic plants did not vary compared to control plants. This study demonstrates the use of MYB transcription factors to improve the production of bioethanol from sugarcane bagasse remaining after sugar extraction.

  5. Sugarcane transgenics expressing MYB transcription factors show improved glucose release

    DOE PAGES

    Poovaiah, Charleson R.; Bewg, William P.; Lan, Wu; ...

    2016-07-15

    In this study, sugarcane, a tropical C4 perennial crop, is capable of producing 30-100 tons or more of biomass per hectare annually. The lignocellulosic residue remaining after sugar extraction is currently underutilized and can provide a significant source of biomass for the production of second-generation bioethanol. As a result, MYB31 and MYB42 were cloned from maize and expressed in sugarcane with and without the UTR sequences. The cloned sequences were 98 and 99 % identical to the published nucleotide sequences. The inclusion of the UTR sequences did not affect any of the parameters tested. There was little difference in plantmore » height and the number of internodes of the MYB-overexpressing sugarcane plants when compared with controls. MYB transgene expression determined by qPCR exhibited continued expression in young and maturing internodes. MYB31 downregulated more genes within the lignin biosynthetic pathway than MYB42. MYB31 and MYB42 expression resulted in decreased lignin content in some lines. All MYB42 plants further analyzed showed significant increases in glucose release by enzymatic hydrolysis in 72 h, whereas only two MYB31 plants released more glucose than control plants. This correlated directly with a significant decrease in acid-insoluble lignin. Soluble sucrose content of the MYB42 transgenic plants did not vary compared to control plants. In conclusion, this study demonstrates the use of MYB transcription factors to improve the production of bioethanol from sugarcane bagasse remaining after sugar extraction.« less

  6. Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice

    PubMed Central

    Membrez, M; Chou, C J; Raymond, F; Mansourian, R; Moser, M; Monnard, I; Ammon-Zufferey, C; Mace, K; Mingrone, G; Binnert, C

    2010-01-01

    Aim: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D). Methods: Three groups of 15 db/db mice were fed for 6 weeks either a chow diet (Ctrl) or a chow diet supplemented with 1.5 or 15% (SA1.5% and SA15%, respectively) energy from SA. Fasting glycaemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results: After 42 days of supplementation, fasting glycaemia and HbA1c were ∼70 and 25% lower in the SA15% group compared with the other groups showing a beneficial effect of SA on hyperglycaemia. During OGTT, plasma glucose area under the curve was reduced after SA15% compared with the other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared with Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusion: Dietary supplementation of SA largely improves glycaemic control in a mouse model of T2D. This beneficial effect may be due to (i) an improved glucose-induced insulin secretion and (ii) a reduced hepatic glucose output. PMID:20977585

  7. Evidence that the oral glucose-tolerance test does not provide a uniform stimulus to pancreatic islets in pregnancy.

    PubMed

    de Leacy, E A; Cowley, D M

    1989-07-01

    Fifty consecutive pregnant patients referred for a glucose-tolerance test were classified on the basis of increasing (n = 20) or decreasing (n = 28) hematocrit after an oral 75-g glucose load. (The hematocrit did not change in the other two patients.) Patients with increasing hematocrit, a response previously seen in patients with the dumping syndrome, showed significantly flatter increases in glucose concentrations in plasma after the load. The mean decrease in the concentration of phosphate in plasma, measured as an index of glucose uptake by cells, was significantly less (P less than 0.05) 2 h after the load in the group with flatter glucose responses, suggesting that the flat response is ascribable to poor glucose absorption rather than to an exaggerated insulin response. These results indicate that the oral glucose-tolerance test stresses the pancreatic islets differently in different pregnant subjects, owing to individual variations in the gastrointestinal handling of the glucose load. Consequently, patients may give a "normal" result who might otherwise become hyperglycemic after normal meals. We suggest that alternative screening procedures be investigated to assess pregnant patients postprandially.

  8. Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity.

    PubMed

    Schernthaner-Reiter, Marie Helene; Kasses, Dominik; Tugendsam, Christina; Riedl, Michaela; Peric, Slobodan; Prager, Gerhard; Krebs, Michael; Promintzer-Schifferl, Miriam; Clodi, Martin; Luger, Anton; Vila, Greisa

    2016-12-01

    Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting. OGTTs were performed in severely obese patients (n = 6) pre- and post-bariatric surgery. Circulating serum GDF15 concentrations were studied in lean and obese individuals in response to different meals, OGTT or short-term fasting, and in severely obese patients pre- and post-bariatric surgery. Regulation of GDF15 mRNA levels and protein release were evaluated in the human hepatic cell line HepG2. GDF15 concentrations steadily decrease during short-term fasting in lean and obese individuals. Carbohydrate- and fat-rich meals do not influence GDF15, whereas an OGTT leads to a late increase in GDF15 levels. The positive effect of OGTT on GDF15 levels is also preserved in severely obese patients, pre- and post-bariatric surgery. We further studied the regulation of GDF15 mRNA levels and protein release in HepG2, finding that glucose and insulin independently stimulate both GDF15 transcription and secretion. In summary, high glucose and insulin peaks upregulate GDF15 transcription and release. The nutrient-induced increase in GDF15 levels depends on rapid glucose and insulin excursions following fast-digesting carbohydrates, but not on the amount of calories taken in. © 2016 European Society of Endocrinology.

  9. Exhaled breath condensate pH decreases following oral glucose tolerance test.

    PubMed

    Bikov, Andras; Pako, Judit; Montvai, David; Kovacs, Dorottya; Koller, Zsofia; Losonczy, Gyorgy; Horvath, Ildiko

    2015-12-15

    Exhaled breath condensate (EBC) pH is a widely measured non-invasive marker of airway acidity. However, some methodological aspects have not been thoroughly investigated. The aim of the study was to determine the effect of oral glucose tolerance test (OGTT) on EBC pH in attempt to better standardize its measurement. Seventeen healthy subjects (24  ±  2 years, 6 men, 11 women) participated in the study. EBC collection and capillary blood glucose measurements were performed before as well as 0, 30, 60 and 120 min after a standardized OGTT test. The rate of respiratory droplet dilution and pH were evaluated in EBC. Blood glucose significantly increased at 30 min and maintained elevation after 60 and 120 min following OGTT. Compared to baseline (7.99  ±  0.25) EBC pH significantly decreased immediately after OGTT (7.41  ±  0.47); this drop sustained over 30 (7.44  ±  0.72) and 60 min (7.62  ±  0.44) without a significant difference at 120 min (7.78  ±  0.26). No change was observed in the rate of respiratory droplet dilution. There was no relationship between blood glucose and EBC pH values. Sugar intake may significantly decrease EBC pH. This effect needs to be considered when performing EBC pH studies. Further experiments are also warranted to investigate the effect of diet on other exhaled biomarkers.

  10. The effect of short-term dietary supplementation with glucose on gastric emptying of glucose and fructose and oral glucose tolerance in normal subjects.

    PubMed

    Horowitz, M; Cunningham, K M; Wishart, J M; Jones, K L; Read, N W

    1996-04-01

    Recent observations indicate that gastric emptying may be influenced by patterns of previous nutrient intake. The aims of this study were to determine the effects of a high glucose diet on gastric emptying of glucose and fructose, and the impact of any changes in gastric emptying on plasma concentrations of glucose, insulin and gastric inhibitory polypeptide in response to glucose and fructose loads. Gastric emptying of glucose and fructose (both 75 g dissolved in 350 ml water) were measured in seven normal volunteers on separate days while each was on a "standard' diet and an identical diet supplemented with 440 g/day of glucose for 4-7 days. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide levels were taken immediately before and for 180 min after ingestion of glucose and fructose loads. Dietary glucose supplementation accelerated gastric emptying of glucose (50% emptying time 82 +/- 8 vs 106 +/- 10 min, p = 0.004) and fructose (73 +/- 9 vs 106 +/- 9 min, p = 0.001). After ingestion of glucose, plasma concentrations of insulin (p < 0.05) and gastric inhibitory polypeptide (p < 0.05) were higher during the glucose-supplemented diet. In contrast, plasma glucose concentrations at 60 min and 75 min were lower (p < 0.05) on the glucose-supplemented diet. We conclude that short-term supplementation of the diet with glucose accelerates gastric emptying of glucose and fructose, presumably as a result of reduced feedback inhibition of gastric emptying from small intestinal luminal receptors. More rapid gastric emptying of glucose has a significant impact on glucose tolerance.

  11. Rapid post-oral stimulation of intake and flavor conditioning by glucose and fat in the mouse

    PubMed Central

    Zukerman, Steven; Ackroff, Karen

    2011-01-01

    Although widely assumed to have only satiating actions, nutrients in the gut can also condition increases in intake in some cases. Here we studied the time course of post-oral nutrient stimulation of ingestion in food-restricted C57BL/6J mice. In experiment 1, mice adapted to drink a 0.8% sucralose solution 1 h/day, rapidly increased their rate of licking (within 4–6 min) when first tested with an 8% glucose solution and even more so in tests 2 and 3. Other mice decreased their licking rate when switched from sucralose to 8% fructose, a sugar that is sweet like glucose but lacks positive post-oral effects in mice. The glucose-stimulated drinking is due to the sugar's post-oral rather than taste properties, because sucralose is highly preferred to glucose and fructose in brief choice tests. A second experiment showed that the glucose-stimulated ingestion is associated with a conditioned flavor preference in both intact and capsaicin-treated mice. This indicates that the post-oral stimulatory action of glucose is not mediated by capsaicin-sensitive visceral afferents. In experiment 3, mice consumed flavored saccharin solutions as they self-infused water or glucose via an intragastric (IG) catheter. The glucose self-infusion stimulated ingestion within 13–15 min in test 1 and produced a conditioned increase in licking that was apparent in the initial minute of tests 2 and 3. Experiment 4 revealed that IG self-infusions of a fat emulsion also resulted in post-oral stimulation of licking in test 1 and conditioned increases in tests 2 and 3. These findings indicate that glucose and fat can generate stimulatory post-oral signals early in a feeding session that increase ongoing ingestion and condition increases in flavor acceptance and preference revealed in subsequent feeding sessions. The test procedures developed here can be used to investigate the peripheral and central processes involved in stimulation of intake by post-oral nutrients. PMID:21975648

  12. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Pillai, Subramanian Iyyam; Subramanian, Sorimuthu Pillai

    2014-10-05

    Liver plays a vital role in blood glucose homeostasis. Recent studies have provided considerable evidence that hepatic glucose production (HGP) plays an important role in the development of fasting hyperglycemia in diabetes. From this perspective, diminution of HGP has certainly been considered for the treatment of diabetes. In the present study, we have analyzed the modulatory effects of fisetin, a flavonoid of strawberries, on the expression of key enzymes of carbohydrate metabolism in STZ induced experimental diabetic rats. The physiological criterions such as food and fluid intake were regularly monitored. The levels of blood glucose, plasma insulin, hemoglobin and glycosylated hemoglobin were analyzed. The mRNA and protein expression levels of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined by immunoblot as well as PCR analysis. Diabetic group of rats showed significant increase in food and water intake when compared with control group of rats. Upon oral administration of fisetin as well as gliclazide to diabetic group of rats, the levels were found to be decreased. Oral administration of fisetin (10 mg/kg body weight) to diabetic rats for 30 days established a significant decline in blood glucose and glycosylated hemoglobin levels and a significant increase in plasma insulin level. The mRNA and protein expression levels of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), were decreased in liver tissues upon treatment with fisetin. The results of the present study suggest that fisetin improves glucose homeostasis by direct inhibition of gluconeogenesis in liver. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. The effect of endurance training and subsequent physical inactivity on glycaemic control after oral glucose load and physical exercise in healthy men

    NASA Astrophysics Data System (ADS)

    Radikova, Zofia; Ksinantova, Lucia; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Vigas, Milan; Koska, Juraj

    2007-02-01

    Physical inactivity during space flight has a profound effect on glucose metabolism. The aim of this study was to test whether endurance training (ET) may improve a negative effect of subsequent -6∘ head-down bed rest (HDBR) on glucose metabolism. Fourteen healthy males completed the study consisting of 6 weeks lasting ET followed by 6 days HDBR. Treadmill exercise at 80% of pre-training VO2max and 75 g oral glucose tolerance test (OGTT) were performed before and after ET as well as after HDBR. ET increased VO2max by 11%. ET significantly lowered while HDBR had no effect on fasting and OGTT plasma glucose levels. ET had no effect while HDBR was followed by an augmentation of insulin and C-peptide response to OGTT. Insulin sensitivity tended to increase after ET and to decrease during HDBR, however, mostly without statistical significance. Plasma glucose, insulin and C-peptide response to exercise were elevated after HDBR only. Our study shows that antecedent physical training could ameliorate a negative effect of simulated microgravity on insulin-mediated glucose metabolism.

  14. Language and Science: Improving Oral Reading.

    ERIC Educational Resources Information Center

    Jeremiah, Milford A.

    Students at the secondary and postsecondary levels exhibit difficulty in the oral reading of scientific terminology, in part because of the abundance of polysyllabic words derived from Greek and Latin. Some of the problems observed include faulty stress placement, vowel insertion and deletion, vowel discrimination, and consonant insertion. Such…

  15. Improving Oral Performance through Interactions Flashcards

    ERIC Educational Resources Information Center

    Urquijo, Jasson

    2012-01-01

    This paper describes an action research project that addressed the issue of low oral performance in English among third grade learners at a public girls' school in Bogota, Colombia. The issue was identified via content analysis of ten field logs compiled over the third and fourth quarter of the second semester, 2010. To address the problem of…

  16. Oral Assessments: Improving Retention, Grades, and Understanding

    ERIC Educational Resources Information Center

    Nelson, Mary A.

    2011-01-01

    This article reports on an innovative approach to teaching Calculus I which was initiated in a two-semester course designed for students at risk of failing Calculus I. The treatment consisted of voluntary oral assessments offered before every written examination. Analyses showed that the treatment students did significantly better than the control…

  17. Novel GPR40 agonist AS2575959 exhibits glucose metabolism improvement and synergistic effect with sitagliptin on insulin and incretin secretion.

    PubMed

    Tanaka, Hirotsugu; Yoshida, Shigeru; Minoura, Hideaki; Negoro, Kenji; Shimaya, Akiyoshi; Shimokawa, Teruhiko; Shibasaki, Masayuki

    2014-01-17

    GPR40 is a free fatty acid receptor that regulates glucose-dependent insulin secretion at pancreatic β-cells and glucagon-like peptide-1 (GLP-1), one of the major incretins, secretion at the endocrine cells of the gastrointestinal tract. We investigated the synergistic effect of AS2575959, a novel GPR40 agonist, in combination with sitagliptin, a major dipeptidyl peptidase-IV (DPP-IV) inhibitor, on glucose-dependent insulin secretion and GLP-1 secretion. In addition, we investigated the chronic effects of AS2575959 on whole-body glucose metabolism. We evaluated acute glucose metabolism on insulin and GLP-1 secretion using an oral glucose tolerance test (OGTT) as well as assessed the chronic glucose metabolism in diabetic ob/ob mice following the repeated administration of AS2575959. We discovered the novel GPR40 agonist sodium [(3S)-6-({4'-[(3S)-3,4-dihydroxybutoxy]-2,2',6'-trimethyl[1,1'-biphenyl]-3-yl}methoxy)-3H-spiro[1-benzofuran-2,1'-cyclopropan]-3-yl]acetate (AS2575959) and found that the compound influenced glucose-dependent insulin secretion both in vitro pancreas β-cell-derived cells and in vivo mice OGTT. Further, we observed a synergistic effect of AS2575959 and DPP-IV inhibitor on insulin secretion and plasma GLP-1 level. In addition, we discovered the improvement in glucose metabolism on repeated administration of AS2575959. To our knowledge, this study is the first to demonstrate the synergistic effect of a GPR40 agonist and DPP-IV inhibitor on the glucose-dependent insulin secretion and GLP-1 concentration increase. These findings suggest that GPR40 agonists may represent a promising therapeutic strategy for the treatment of type 2 diabetes mellitus, particularly when used in combination with DPP-IV inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Ferulic acid improves lipid and glucose homeostasis in high-fat diet-induced obese mice.

    PubMed

    Naowaboot, Jarinyaporn; Piyabhan, Pritsana; Munkong, Narongsuk; Parklak, Wason; Pannangpetch, Patchareewan

    2016-02-01

    Ferulic acid (FA) is a plant phenolic acid that has several pharmacological effects including antihyperglycaemic activity. Thus, the objective of this study is to investigate the effect of FA on glucose and lipid metabolism in high-fat diet (HFD)-induced obese mice. Institute for Cancer Research (ICR) mice were fed a HFD (45 kcal% fat) for 16 weeks. At the ninth week of induction, the obese mice were orally administered with daily FA doses of 25 and 50 mg/kg for the next eight weeks. The results show that FA significantly reduced the elevated blood glucose and serum leptin levels, lowered the insulin resistance, and increased the serum adiponectin level. Moreover, serum lipid level, and liver cholesterol and triglyceride accumulations were also reduced. The histological examination showed clear evidence of a decrease in the lipid droplets in liver tissues and smaller size of fat cells in the adipose tissue in the obese mice treated with FA. Interestingly, FA reduced the expression of hepatic lipogenic genes such as sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). It could also up-regulate hepatic carnitine palmitoyltransferase 1a (CPT1a) gene and peroxisome proliferator-activated receptor alpha (PPARα) proteins. The FA treatment was also found to suppress the protein expressions of hepatic gluconeogenic enzymes, phosphoenolpyruvate carboxylase (PEPCK) and glucose-6-phosphatase (G6Pase). In conclusion, the findings of this study demonstrate that FA improves the glucose and lipid homeostasis in HFD-induced obese mice probably via modulating the expression of lipogenic and gluconeogenic genes in liver tissues.

  19. Sodium salicylate restores the impaired insulin response to glucose and improves glucose tolerance in heroin addicts.

    PubMed

    Giugliano, D; Quatraro, A; Consoli, G; Stante, A; Simeone, V; Ceriello, A; Paolisso, G; Torella, R

    1987-01-01

    Plasma glucose, insulin, C-peptide, glucagon and growth hormone responses to intravenous glucose were evaluated in 10 heroin addicts in the basal state and during an infusion of sodium salicylate, an inhibitor of endogenous prostaglandin synthesis. Ten normal subjects, matched for age, sex and weight served as controls. In the basal state, the heroin addicts had markedly reduced insulin responses to intravenous glucose and low glucose disappearance rates (p less than 0.01 vs controls). The infusion of sodium salicylate caused a striking increase of the acute insulin response to intravenous glucose (from 14.5 +/- 4 microU/ml to 88 +/- 11 microU/ml, p less than 0.001) and restored to normal the reduced glucose tolerance (KG from 1.10 +/- 0.1% min-1 to 2.04 +/- 0.19% min-1). Hypoglycemic values were found in all addicts at the end of the test during salicylate infusion. Indomethacin pretreatment in five additional addicts also caused normalization of the impaired insulin responses to the intravenous glucose challenge and restored to normal the reduced glucose disappearance rate. Plasma glucagon and growth hormone levels were normally suppressed by glucose in addicts in basal conditions; sodium salicylate infusion completely overturned these hormonal responses which became positive in the first 15 min following the glucose challenge. These results demonstrate that the two prostaglandin synthesis inhibitors can restore the impaired B-cell response to glucose in heroin addicts to normal, indicating that this response is not lost but is inhibited by heroin itself or by other substances, perhaps by the endogenous prostaglandins.

  20. Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.

    PubMed

    Van Proeyen, Karen; Ramaekers, Monique; Pischel, Ivo; Hespel, Peter

    2012-08-01

    The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a double-blind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTT(R)), a 30-min cycling bout at ~75% VO(2max), and another OGTT after exercise (OGTT(EX)). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTT(R). Blood samples were collected before (t₀) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTT(EX) an additional 75-g oral glucose bolus was administered at t₆₀. In OGTT(R), OFI administration reduced the area under the glucose curve (AUC(GLUC)) by 26%, mainly due to lower blood glucose levels at t₃₀ and t₆₀ (p < .05). Furthermore, a higher serum insulin concentration was noted after OFI intake at baseline and at t₃₀ (p < .05). In OGTT(EX), blood glucose at t₆₀ was ~10% lower in OFI than in PL, which resulted in a decreased AUC(GLUC) (-37%, p < .05). However, insulin values and AUC(INS) were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

  1. Evaluation of a Minimally Invasive System for Measuring Glucose Area under the Curve during Oral Glucose Tolerance Tests: Usefulness of Sweat Monitoring for Precise Measurement

    PubMed Central

    Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Hamaguchi, Tomoya; Toshihiro, Matsuo; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi; Sato, Toshiyuki; Okada, Seiki; Tomita, Koji; Matsuhisa, Munehide; Kaneto, Hideaki; Kosugi, Keisuke; Maegawa, Hiroshi; Nakajima, Hiromu; Kashiwagi, Atsunori

    2013-01-01

    Aims: We developed a system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET). Sweat contamination during interstitial fluid glucose (IG) extraction affects the accuracy of glucose AUC measurement, because this technology uses extracted sodium ion levels as an internal standard. Therefore, we developed a sweat monitoring patch to reduce this effect and investigated its efficacy in volunteers undergoing oral glucose tolerance tests (OGTTs). Materials and Methods: Fifty diabetes mellitus inpatients and 10 healthy subjects undergoing the 75 g OGTT were included. Two sites on the forearm were pretreated with microneedle arrays, then hydrogels for interstitial fluid extraction were placed on the treated sites. Simultaneously, hydrogels for sweat monitoring were placed on untreated sites near the treated sites. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference AUC values. Using MIET, IG AUC was calculated from extracted glucose and sodium ion levels after attachment of the hydrogel for 2 h. Results: Good correlation between IG AUC measurements using MIET and reference AUCs measured using PG levels was confirmed over a wide AUC range (202–610 mg/h/dl) after correction for the sweat-induced error detected by the hydrogel patches on the nonpretreated skin. Strong correlation between IG AUC and peak glucose levels indicates that glucose spikes can be easily detected by this system. Conclusion: We confirmed the effectiveness of a sweat monitoring patch for precise AUC measurement using MIET. This novel, easy-to-use system has potential for glucose excursion evaluation in daily clinical practice. PMID:23759401

  2. Improvement of glucose intolerance by combination of pravastatin and olmesartan in type II diabetic KK-A(y) mice.

    PubMed

    Kanno, Harumi; Iwai, Masaru; Inaba, Shinji; Senba, Izumi; Nakaoka, Hirotomo; Sone, Hisako; Mogi, Masaki; Horiuchi, Masatsugu

    2009-08-01

    The effects of the coadministration of pravastatin and an angiotensin type 1 (AT(1)) receptor blocker, olmesartan, on glucose intolerance were examined using type II diabetic mice. Male KK-A(y) mice (8 weeks of age) were treated with pravastatin and/or olmesartan for 2 weeks. An oral glucose tolerance test (OGTT) was performed with an administration of 2 g kg(-1) glucose. Tissue glucose uptake was determined using 2-[(3)H]deoxyglucose. The treatment of mice with pravastatin attenuated the increase in the plasma glucose level during OGTT in a dose-dependent manner, without affecting the plasma insulin level. Pravastatin increased glucose uptake in insulin-sensitive tissue such as the skeletal muscle and adipose tissue after treatment at 5-20 mg kg(-1) day(-1) for 2 weeks, but not at 1 mg kg(-1) day(-1). The combination of a noneffective dose of pravastatin (1 mg kg(-1) day(-1)) and a noneffective dose of olmesartan (0.5 mg kg(-1) day(-1)) synergistically improved OGTT without affecting the plasma insulin level. This combination also increased 2-[(3)H]deoxyglucose uptake in the skeletal muscle and adipose tissue. The effects of pravastatin or olmesartan on OGTT and tissue 2-[(3)H]deoxyglucose uptake were significantly enhanced by an antioxidant, tempol, whereas the effects of a pravastatin-olmesartan combination were not further enhanced by tempol. These results indicate that the combination of pravastatin and olmesartan synergistically improves glucose intolerance through an increase in tissue glucose uptake. The effects seem to be mediated by an increase in insulin sensitivity through the inhibition of oxidative stress.

  3. 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.

  4. Growth hormone after oral glucose overload: revision of reference values in normal subjects.

    PubMed

    Rosário, Pedro W S; Furtado, Mariana S

    2008-10-01

    The evaluation of growth hormone (GH) secretion continues to be important in acromegaly and the nadir GH (n-GH) level in the oral glucose tolerance test (OGTT) is the gold standard for the demonstration of secretory autonomy of this hormone. n-GH levels < 1 microg/L are defined as normal suppression but, using current assays, n-GH < 1 microg/L is detected in patients with untreated acromegaly and this value seems to be much lower in normal subjects. The objective of the present study was to evaluate n-GH levels in the OGTT in normal subjects using three different assays (GH ICMA Immulite; GH IRMA DSL and GH IFMA AutoDelfia). Two-hundred apparently healthy subjects (120 women) ranging in age from 18 to 70 years and with a BMI > 18.5 and < 27 kg/m(2), who used no medications and presented normal glycemia, blood count, albumin, creatinine, TSH, SGOT, SGPT and bilirubin were studied. Serum samples were obtained before and 30,60,90 and 120 min after oral administration of 75 g glucose. The test was repeated after 4 weeks in 157 participants, with the same protocol being used in 79 and 78 receiving an overload of 100 g glucose. n-GH cut-off values (97.5th percentile) were higher in women than in men (GH-IFMA: 0.30 versus 0.11 microg/L; GH-ICMA: 0.60 versus 0.25 microg/L; GH-IRMA: 0.20 versus 0.10 microg/L, respectively). No correlation was observed between n-GH and age or BMI. A difference was only observed when comparing women < 35 years (n = 40) versus > 35 years (n = 80), with higher values in the former (n-GH cut-off in this subgroup: GH-IFMA 0.40 versus 0.26 microg/L, GH-ICMA 0.74 versus 0.50 microg/L, GH-IRMA 0.25 versus 0.15 microg/L). A good correlation was observed between the assays (r = 0.9-0.96), however, the highest values were always obtained with the Immulite assay. Test repetition with 75 g oral glucose showed a variation in n-GH < 10.2% (GH-IFMA), < 13.4% (GH-ICMA) and < 11% (GH-IRMA) in 95% of the subjects. This variation was similar when the test was

  5. Sugarcane transgenics expressing MYB transcription factors show improved glucose release

    SciTech Connect

    Poovaiah, Charleson R.; Bewg, William P.; Lan, Wu; Ralph, John; Coleman, Heather D.

    2016-07-15

    In this study, sugarcane, a tropical C4 perennial crop, is capable of producing 30-100 tons or more of biomass per hectare annually. The lignocellulosic residue remaining after sugar extraction is currently underutilized and can provide a significant source of biomass for the production of second-generation bioethanol. As a result, MYB31 and MYB42 were cloned from maize and expressed in sugarcane with and without the UTR sequences. The cloned sequences were 98 and 99 % identical to the published nucleotide sequences. The inclusion of the UTR sequences did not affect any of the parameters tested. There was little difference in plant height and the number of internodes of the MYB-overexpressing sugarcane plants when compared with controls. MYB transgene expression determined by qPCR exhibited continued expression in young and maturing internodes. MYB31 downregulated more genes within the lignin biosynthetic pathway than MYB42. MYB31 and MYB42 expression resulted in decreased lignin content in some lines. All MYB42 plants further analyzed showed significant increases in glucose release by enzymatic hydrolysis in 72 h, whereas only two MYB31 plants released more glucose than control plants. This correlated directly with a significant decrease in acid-insoluble lignin. Soluble sucrose content of the MYB42 transgenic plants did not vary compared to control plants. In conclusion, this study demonstrates the use of MYB transcription factors to improve the production of bioethanol from sugarcane bagasse remaining after sugar extraction.

  6. Effects of oral glucose on exercise thermoregulation in men after water immersion

    NASA Technical Reports Server (NTRS)

    Dearborn, Alan S.; Ertl, Andrew C.; Greenleaf, John E.; Barnes, Paul R.; Jackson, Catherine G. R.; Breckler, Jennifer L.

    1994-01-01

    To test the hypothesis elevated blood glucose would attenuate the rise in exercise rectal temperature, six men age 35 plus or minus S.D. 7 years participated in each of three trials by 4-hr water immersion to the neck: (1) 2.0 g/kg body wt of oral glucose (33.8 percent wt./vol.) was consumed followed by 80 min controlled rest (Glu/Rest), and 70 min horizontal supine cycle exercise at 62.8 percent plus or minus S.E. 0.5 percent (1.97 plus or minus 0.02 L/min) of peak O2 uptake followed by 10 min recovery (2) with (Glu/Ex) and (3) without prior flucose (No Glu/Ex). Blood samples were taken at -25, 0, 15, 45, and 68 min of exercise and after plus 10 min of recovery for measurement of hemoglobin, hematocrit, and blood glucose. Both mean skin (T sub sk) (from six sites) and rectal temperatures (T sub re) were monitored continuously. Sweat rate was measured by resistanc hygrometry. The mean of delta PV for the exercise trials was -12.2 plus or minus 2.1 percent. Mean blood glucose for the Glu/Ex trial was higher than that of the No Glu/Ex trial was (108.4 equal or minus 3.9 and 85.6 plus or minus 1.6 mg/dl, respectively, P less than 0.05. At the end of exercise T(sub sk) for the Glu/Ex trial was lower than for No Glu/Ex(32.0 plus or minus 0.3 and 32.4 equals or minus 0.2 C, respectively, P less than 0.05); T(sub re) for the Glu/Ex trial was lower than for No Glu/Es (38.22 plus or minus 0.17 and 38.60 plus or minus 0.11 C, respectively, P less than 0.05); and forearm sweat rate for the Glu/Ex trial (0.34 plus or minus 0.04 and 0.43 plus or minus g/sq cm, respectively, P less than 0.05). These data suggest that elevation of blood glucose prior to horizontal exercise following hypohydration attenuates the increase in body temperature without altering heat production or exercise hypovolemia.

  7. Berberine Improves Glucose Homeostasis in Streptozotocin-Induced Diabetic Rats in Association with Multiple Factors of Insulin Resistance

    PubMed Central

    Chen, Yanfeng; Wang, Yanwen; Zhang, Junzeng; Sun, Changhao; Lopez, Alfonso

    2011-01-01

    The present study was carried out to determine the effect of berberine on glucose homeostasis and several biomarkers associated with insulin sensitivity in male Wistar rats with intraperitoneal injection of streptozotocin (STZ)-induced diabetes. Rats with fasting blood glucose 16.7 mmol/L after 2 weeks of STZ injection were divided into two groups. One group was used as the diabetic control and another treated by gavage feeding with 100 mg/kg/d of berberine in water containing 0.5% carboxymethyl cellulose. A group of rats without receiving STZ was used as the normal control. After 7 weeks, berberine supplementation moderately but significantly lowered fasting blood glucose levels and improved oral glucose tolerance. Berberine lowered plasma free fatty acids and C-reactive protein levels without affecting plasma insulin levels. Diabetic rats treated with berberine showed significantly lower plasma triacylglycerol and cholesterol levels. Furthermore, berberine inhibited dipeptidyl peptidase-4 and protein tyrosine phosphatase-1B activities. In conclusion, berberine showed a dramatic effect of lowering blood cholesterol and triacylglycerols and improved moderately glucose homeostasis in STZ-induced diabetic rats in association with multiple factors related to insulin resistance. PMID:22363882

  8. Effects of basswood honey, honey-comparable glucose-fructose solution, and oral glucose tolerance test solution on serum insulin, glucose, and C-peptide concentrations in healthy subjects.

    PubMed

    Münstedt, Karsten; Sheybani, Babak; Hauenschild, Annette; Brüggmann, Dörthe; Bretzel, Reinhard G; Winter, Daniel

    2008-09-01

    Studies suggest that honey has less influence on serum glucose concentrations than monosaccharides and disaccharides. This study aimed to confirm these findings conclusively by comparing directly the effects of honey, an identical sugar solution, and oral glucose tolerance (OGT) test solution on serum glucose, insulin, and C-peptide values in healthy subjects. Twelve healthy men with a mean age of 27.7 years, a mean body mass index of 23.2 kg/m(2), and no history of metabolic disorders participated in the study. Subjects underwent OGT testing to establish values and exclude preclinical diabetes. One week later they were randomly assigned to basswood honey or a glucose-fructose solution (honey-comparable glucose-fructose solution). The following week subjects were given the other solution. All solutions contained 75 g of glucose. Serum glucose was measured before drinking test solutions and every 10 minutes for 120 minutes afterwards. C-peptide and insulin were measured at 60 and 120 minutes. Serum insulin and C-peptide values at 60 minutes were significantly lower for honey. The mean serum glucose concentration was also lower for honey, but direct comparisons at the various times showed no statistically significant differences between solutions. However, the area under the concentration-time profile for glucose response was lower for the honey than the honey-comparable glucose-fructose solution. Honey had less effect on serum glucose, C-peptide, and insulin values than the honey-comparable glucose-fructose solution. Further study to elucidate underlying mechanisms may be worthwhile, as may investigation of the implications of these findings for diabetic patients.

  9. Oral glucose tolerance test effects on endothelial inflammation markers in healthy subjects and diabetic patients.

    PubMed

    Derosa, G; D'Angelo, A; Salvadeo, S A T; Ferrari, I; Fogari, E; Gravina, A; Mereu, R; Palumbo, I; Maffioli, P; Randazzo, S; Cicero, A F G

    2010-01-01

    The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

  10. Cardiovascular disease and oral agent glucose-lowering therapies in the management of type 2 diabetes.

    PubMed

    Home, Philip

    2012-06-01

    Although glucose-lowering oral agents have been available for clinical use for over 60 years, the formal evidence base supporting their advantage and safety in regard of cardiovascular (CV) outcomes remains less than optimal. However, a synthesis of the evidence results in a high probability of benefit. For metformin, the United Kingdom Prospective Diabetes Study (UKPDS) substudy is convincing for a definite effect in reducing myocardial infarction (MI), but the quantitative extent of that is uncertain. For sulfonylureas, support for reduction in MI comes from the UKPDS extension study, where the central estimate for risk reduction remains the same as in the original planned end to the study, but the greater number of events was statistically significant for the sulfonylurea/insulin arm. Other studies do not support the view that metformin and sulfonylureas differ with respect to MI or indeed CV outcomes more generally. The data available for acarbose, an α-glucosidase inhibitor, are weak but not of concern, although some positive substudy data are available for people with impaired glucose tolerance. For peroxisome proliferator-activated receptor-γ agonists the CV data are more controversial, but the purpose-designed randomized controlled trials are clear that pioglitazone is advantageous to placebo (except for heart failure [HF]), whereas rosiglitazone is indistinguishable from metformin/sulfonylureas (even when including HF data). Lower-quality data do, however, lead to significant concerns for MI with rosiglitazone. Early and somewhat low-quality data for the dipeptidyl peptidase inhibitors show they are safe and hold promise for cardiovascular advantage, with major randomized controlled trials being underway. Preliminary CV data are available for one sodium/glucose cotransporter 2 inhibitor and look reassuring.

  11. Quality Improvement: Indigenous Influence in Oral Health Policy, Process, and Practice.

    PubMed

    Makowharemahihi, Charrissa; Wall, Justin; Keay, Greg; Britton, Cheryl; McGibbon, Minnie; LeGeyt, Patrick; Maipi, Joyce; Signal, Virginia

    2016-02-01

    A Quality Improvement Group for Māori oral health providers [Indigenous New Zealand oral health services] has been an effective and necessary mechanism for engaging Indigenous oral health expertise in decision-making for Indigenous oral health policy and sector developments to reduce oral health inequalities and improve Indigenous oral health outcomes.

  12. Nanolayer encapsulation of insulin-chitosan complexes improves efficiency of oral insulin delivery

    PubMed Central

    Song, Lei; Zhi, Zheng-liang; Pickup, John C

    2014-01-01

    Current oral insulin formulations reported in the literature are often associated with an unpredictable burst release of insulin in the intestine, which may increase the risk for problematic hypoglycemia. The aim of the study was to develop a solution based on a nanolayer encapsulation of insulin-chitosan complexes to afford sustained release after oral administration. Chitosan/heparin multilayer coatings were deposited onto insulin-chitosan microparticulate cores in the presence of poly(ethylene) glycol (PEG) in the precipitating and coating solutions. The addition of PEG improved insulin loading and minimized an undesirable loss of the protein resulting from redissolution. Nanolayer encapsulation and the formation of complexes enabled a superior loading capacity of insulin (>90%), as well as enhanced stability and 74% decreased solubility at acid pH in vitro, compared with nonencapsulated insulin. The capsulated insulin administered by oral gavage lowered fasting blood glucose levels by up to 50% in a sustained and dose-dependent manner and reduced postprandial glycemia in streptozotocin-induced diabetic mice without causing hypoglycemia. Nanolayer encapsulation reduced the possibility of rapid and erratic falls of blood glucose levels in animals. This technique represents a promising strategy to promote the intestinal absorption efficiency and release behavior of the hormone, potentially enabling an efficient and safe route for oral insulin delivery of insulin in diabetes management. PMID:24833901

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

    PubMed Central

    Zukerman, Steven; Ackroff, Karen

    2014-01-01

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

  14. 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

    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

    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. 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. Follow-up of clinical trial. 504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c. Relative risk of CVD. 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. 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.

  15. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance

    PubMed Central

    Sayers, Sophie R.; Reimann, Frank; Gribble, Fiona M.; Parker, Helen; Zac-Varghese, Sagen; Bloom, Stephen R.; Foretz, Marc; Viollet, Benoit; Rutter, Guy A.

    2016-01-01

    Background Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1) in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK) in these cells. Method Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre) to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay. Results Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01) in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01) and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01) GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01). Conclusion AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes. PMID:27010458

  16. Plasma triglycerides after oral glucose load specifically associate with metabolic risk markers in healthy type 2 diabetes offspring.

    PubMed

    Vossen, Michaela; Tödter, Klaus; Altenburg, Christiane; Beisiegel, Ulrike; Scheja, Ludger

    2011-07-01

    To assess the potential of plasma triglycerides measured after glucose load as biomarker for insulin resistance and cardiovascular risk. An oral glucose tolerance test (OGTT, n=91) was performed in healthy type 2 diabetes offspring. Plasma lipids, lipoproteins, glucose and hormones were quantified in fasting and post-challenge samples. During the OGTT total plasma triglycerides decreased in most subjects, however, they increased in some individuals and this increase was strongly associated with metabolic risk factors. Subjects with increasing triglycerides (n=18) were more obese and insulin resistant than those with the most pronounced triglyceride decrease (n=18), as indicated by higher HOMA-IR, BMI and waist circumference. Correlation analysis (n=91) demonstrated that the changes of total plasma and VLDL-associated triglycerides between 0 h and 2 h (Δ-TG, Δ-VLDL-T) were strongly associated with risk factors. Δ-TG, and especially Δ-VLDL-T, correlated better than fasting triglycerides with waist circumference, waist-to-hip ratio and fasting glucose. The correlations remained significant after adjustment for gender, age and HDL cholesterol. The observed increase of triglycerides after glucose load in subjects with signs of insulin resistance and obesity suggests that post-glucose triglyceride change is a potential novel biomarker for early detection of metabolic risk. The specific association of post-glucose triglyceride change with abdominal obesity and fasting glucose suggests a link to hepatic steatosis and insulin resistance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.

    PubMed

    Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

    2014-05-01

    Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes

    PubMed Central

    Scully, Michael S.; Ort, Tatiana A.; James, Ian E.; Bugelski, Peter J.; Makropoulos, Dorie A.; Deutsch, Heather A.; Pieterman, Elsbet J.; van den Hoek, Anita M.; Havekes, Louis M.; duBell, William H.; Wertheimer, Joshua D.; Picha, Kristen M.

    2011-01-01

    Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of 14C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude. PMID:21754921

  19. New-onset diabetes after transplantation--role of oral glucose tolerance test for diagnosis and study of risk factors.

    PubMed

    Sahay, Manisha; Sahay, Rakesh K; Narayan, Girish

    2013-09-01

    To determine the role of the oral glucose tolerance test in the early detection of new-onset diabetes after transplantation (NODAT) and to compare the various risk factors and insulin kinetics in the transplant patients, we studied 41 live-related renal allograft recipients who were not diabetic before transplantation. Immunosuppression included triple drug therapy (cyclosporine, azathioprine and steroids) and rejection episodes were treated with methyl prednisolone (30 mg/kg IV × 3 days). All the study patients were subjected to an oral glucose tolerance test (OGTT) at Day 90 post-transplant and classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and NODAT as per the World Health Organization guidelines. Insulin levels were also determined at 0, ½ hour, 1 hour and 2 hours during OGTT. NODAT was noted in 29.2% of the study patients, IFG in 4.8% of the study patients and NGT in 65.8% of the study patients. All the groups had normal fasting plasma glucose, but higher than normal insulin levels, suggesting insulin resistance. The patients with overt NODAT had, in addition, low fasting insulin (insulin secretory defect). OGTT may be used for the early detection of NODAT. Although insulin resistance is detected in the majority of post-transplant patients, NODAT also reveals also an insulin secretory defect.

  20. Evaluation of myocardial viability with thallium-201 infusion MPSPECT after oral glucose application in patients with chronic coronary artery disease.

    PubMed

    Hasbek, Zekiye; Turgut, Bulent; Erselcan, Taner; Yalta, Kenan; Tandogan, Izzet; Ozer, Gurkan; Ozdemir, Umit; Turgut, Nergiz Hacer

    2009-10-01

    The aim of this study was to evaluate the myocardial viability in nondiabetic patients with chronic coronary artery disease (CCAD) or past myocardial infarction (MI), using thallium-201 infusion myocardial perfusion single-photon emission computed tomography (MPSPECT) imaging after oral glucose application (Glu+Tl-infusion). In this study, 33 nondiabetic patients (three female, 30 male, mean age: 55.24+/-11 years, range: 33-77 years) with MI history or known CCAD were included. Rest/redistribution/24 h-late-MPSPECT imaging was performed for all patients. In all patients in whom fixed perfusion defect was observed on any wall of the left ventriculi, after 24 h-late-MPSPECT imaging, 75 g oral glucose was given. Thirty minutes later, 1 mCi thallium-201 in 100 ml of physiological saline solution was applied in a period of 20 min by slow infusion. After infusion at the 10th minute, MPSPECT imaging was performed. Perfusion was evaluated visually for a total of 3432 segments with the 26-segment 5-point scoring technique. Scoring measured perfusion as 0 = no perfusion defect, 1 = mildly reduced, 2 = moderately reduced, 3 = severely reduced, and 4 = absent uptake. Scores '0 and 1' were considered normal and scores '2-4' were considered abnormal. For serum insulin levels measured after glucose application, a significant increase was determined, according to the period before glucose application (P<0.001). When compared with rest MPSPECT images, segmental perfusion improvement both in redistribution and in the 24 h-late-MPSPECT images were 16.3 and 18.3%, respectively. This ratio was found to be 27.2% for Glu+Tl-infusion images. The ratios of segments in which perfusion was worsening were calculated to be 9.4, 14.5, and 7.3%, respectively, for redistribution, 24 h-late-MPSPECT, and Glu+Tl-infusion images. When this evaluation was made for all three vessel areas, again the highest perfusion improvement and the lowest perfusion worsening were detected for Glu+Tl-infusion images

  1. High phenolics Rutgers Scarlet Lettuce improves glucose metabolism in high fat diet-induced obese mice.

    PubMed

    Cheng, Diana M; Roopchand, Diana E; Poulev, Alexander; Kuhn, Peter; Armas, Isabel; Johnson, William D; Oren, Andrew; Ribnicky, David; Zelzion, Ehud; Bhattacharya, Debashish; Raskin, Ilya

    2016-11-01

    The ability of high phenolic Rutgers Scarlet Lettuce (RSL) to attenuate metabolic syndrome and gut dysbiosis was studied in very high fat diet (VHFD)-fed mice. Phenolic absorption was assessed in vivo and in a gastrointestinal tract model. Mice were fed VHFD, VHFD supplemented with RSL (RSL-VHFD) or store-purchased green lettuce (GL-VHFD), or low-fat diet (LFD) for 13 weeks. Compared to VHFD or GL-VHFD-fed groups, RSL-VHFD group showed significantly improved oral glucose tolerance (p<0.05). Comparison of VHFD, RSL-VHFD, and GL-VHFD groups revealed no significant differences with respect to insulin tolerance, hepatic lipids, body weight gain, fat mass, plasma glucose, triglycerides, free fatty acid, and lipopolysaccharide levels, as well as relative abundances of major bacterial phyla from 16S rDNA amplicon data sequences (from fecal and cecal samples). However, RSL and GL-supplementation increased abundance of several taxa involved in plant polysaccharide degradation/fermentation. RSL phenolics chlorogenic acid, quercetin-3-glucoside, and quercetin-malonyl-glucoside were bioaccessible in the TIM-1 digestion model, but had relatively low recovery. RSL phenolics contributed to attenuation of post-prandial hyperglycemia. Changes in gut microbiota were likely due to microbiota accessible carbohydrates in RSL and GL rather than RSL phenolics, which may be metabolized, absorbed, or degraded before reaching the colon. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Oral hypertonic electrolyte-glucose/mosapride complex solution for resuscitation of burn shock in dogs.

    PubMed

    Hu, Quan; Chai, Jiake; Hu, Sen; Zhou, Guoyong; Sheng, Zhiyong

    2012-01-01

    The objective of this study is to investigate the effect of oral feeding of an electrolyte glucose mosapride solution for resuscitation in dogs with shock after a 35% TBSA full-thickness burn and the effect of mosapride on gastric emptying time. Eighteen male Beagle dogs were randomly divided into intravenous isotonic solution group, intragastric hypertonic solution group, and mosapride group after they were subjected to a 35% TBSA full-thickness flame injury. In intravenous isotonic solution group (I group), isotonic electrolyte glucose solution was given through vein with adoption of the Parkland formula. The resuscitation fluid in intragastric hypertonic solution group (H group) and mosapride group (M group) consisted of 1.8% NaCl and 5% glucose, the total fluid volume was one half of that for I group, and it was given in divided amount every 2 hours. Mosapride was added to the resuscitation fluid in mosapride group. Fluid replacement was begun 30 minutes after the injury in all the groups. Mean arterial pressure (MAP), cardiac output index (CI), intrathoracic blood volume index (ITBI), blood volume (BV), serum sodium concentration, intestinal mucosal blood flow (IMBF), gastric emptying, and serum motilin levels were determined at different time points. The urinary output of all animals was measured immediately after burn upto 360 minutes postburn. CI, ITBI, BV, and IMBF were all decreased obviously after burn. In I group and M group, CI, ITBI, BV, and IMBF were increased gradually after resuscitation, and they were significantly higher than that of H group (P < .05). MAP in all three groups was lowered significantly and then gradually recovered, showing no significant difference among groups. The urinary output in M group was similar to that in I group (P > .05), and it was higher than that in H group (P < .05). Serum sodium level in H group and M group increased in varying degrees and were markedly higher compared with the I group (P < .05). Postburn gastric

  3. The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes.

    PubMed

    Ismail, Heba M; Xu, Ping; Libman, Ingrid M; Becker, Dorothy J; Marks, Jennifer B; Skyler, Jay S; Palmer, Jerry P; Sosenko, Jay M

    2017-09-27

    We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion. Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627). A monophasic curve was defined as an increase in OGTT glucose between 30 and 90 min followed by a decline of ≥ 0.25 mmol/l between 90 and 120 min. A biphasic response curve was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 0.25 mmol/l. Associations of type 1 diabetes risk with glucose curve shapes were examined using cumulative incidence curve comparisons and proportional hazards regression. C-peptide responses were compared with and without adjustments for potential confounders. The majority of participants had a monophasic curve at baseline (n = 1732 [66%] vs n = 895 [34%]). The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). Compared with the biphasic group, the monophasic group had a lower early C-peptide (30-0 min) response, a lower C-peptide index (30-0 min C-peptide/30-0 min glucose), as well as a greater 2 h C-peptide level (p < 0.001 for all). Those with biphasic glucose curves have a lower risk of progression to type 1 diabetes than those with monophasic curves, and the risk among the monophasic group is increased when the glucose peak occurs at 90 min than at 30 min. Differences in glucose curve shapes between

  4. Exploring the Frequency Domain of Continuous Glucose Monitoring Signals to Improve Characterization of Glucose Variability and of Diabetic Profiles.

    PubMed

    Fico, Giuseppe; Hernández, Liss; Cancela, Jorge; Isabel, Miguel María; Facchinetti, Andrea; Fabris, Chiara; Gabriel, Rafael; Cobelli, Claudio; Arredondo Waldmeyer, María Teresa

    2017-07-01

    Continuous glucose monitoring (CGM) devices measure interstitial glucose concentrations (normally every 5 minutes), allowing observation of glucose variability (GV) patterns during the whole day. This information could be used to improve prescription of treatments and of insulin dosages for people suffering diabetes. Previous efforts have been focused on proposing indices of GV either in time or glucose domains, while the frequency domain has been explored only partially. The aim of this work is to explore the CGM signal in the frequency domain to understand if new indexes or features could be identified and contribute to a better characterization of glucose variability. The direct fast Fourier transform (FFT) and the Welch method were used to analyze CGM signals from three different profiles: people at risk of developing type 2 diabetes (P@R), T2D patients, and type 1 diabetes (T1D) patients. The results suggests that features extracted from the FFT (ie, the localization and power of the maximum peak of the power spectrum and the bandwidth at 3 dB) are able to provide a characterization for all the three populations under study compared with the Welch approach. Such preliminary results can represent a good insight for futures investigations with the possibility of building and using new indexes of glucose variability based on the frequency features.

  5. Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea.

    PubMed

    Wapnir, R A; Litov, R E; Zdanowicz, M M; Lifshitz, F

    1991-04-01

    Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1 +/- 0.62 versus 1.5 +/- 0.48 microliters/[min x cm], p less than 0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p less than 0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5 +/- 0.36 and 2.4 +/- 0.38, respectively, versus 0.87 +/- 0.40 microliters/[min x cm], p less than 0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r = -0.653, p less than 0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will

  6. Filling the gap: strategies for improving oral health.

    PubMed

    2001-05-16

    As part of its continuing mission to serve trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH) convened, with the Children's Dental Health Project (CDHP), a select group of grantmakers and national experts who have made a major commitment to improving oral health. This Issue Dialogue - held on May 16,2001, in Washington, DC - explored current challenges related to oral health in the United States, and highlighted public and private sector initiatives to overcome these challenges. The roundtable also illustrated current activities and future opportunities for foundations in the area of oral health. This Issue Brief synthesizes key points from the day's discussion with a background paper previously prepared for Issue Dialogue participants. It includes quantitative and qualitative information on oral health as well as profiles of public sector, private sector, and grantmaker strategies for promoting improvements.

  7. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals

    PubMed Central

    Simon, R R; Marks, V; Leeds, A R; Anderson, J W

    2011-01-01

    Glucosamine (GlcN) is a widely utilized dietary supplement that is used to promote joint health. Reports that oral GlcN supplementation at usual doses adversely affects glucose metabolism in subjects with impaired glucose tolerance have raised concerns that GlcN should be contraindicated in individuals with diabetes and those at risk for developing it. This review addresses its potential, when used at typical doses, to affect glucose metabolism and insulin sensitivity in healthy individuals and those with diabetes or ‘pre-diabetes’. Publicly available scientific information and data on GlcN were systematically compiled using the electronic search tool, Dialog®, and reviewed with special emphasis on human studies. In long-term clinical trials, including those containing subjects with type 2 diabetes or ‘pre-diabetes’, GlcN produced a non-significant lowering of fasting blood glucose concentrations in all groups of subjects treated for periods of up to 3 years. Owing to limitations in study design, conclusions based on studies that report adverse affects of GlcN on insulin sensitivity and glucose tolerance in pre-diabetic subjects are suspect. However, no definitive long-term studies of GlcN use for individuals with pre-diabetes are available. Nevertheless, based on available evidence, we conclude that GlcN has no effect on fasting blood glucose levels, glucose metabolism, or insulin sensitivity at any oral dose level in healthy subjects, individuals with diabetes, or those with impaired glucose tolerance. Copyright © 2010 John Wiley & Sons, Ltd. PMID:21218504

  8. Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats.

    PubMed

    Nagareddy, Prabhakara Reddy; Vasudevan, Harish; McNeill, John H

    2005-05-01

    Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.

  9. Shuttle-box avoidance learning in mice: improvement by combined glucose and tacrine.

    PubMed

    Pavone, F; Capone, F; Battaglia, M; Sansone, M

    1998-03-01

    Glucose and the acetylcholinesterase inhibitor tacrine were tested, alone and in combination, in mice of the CD-1 strain subjected to five daily shuttle-box training sessions. Pretraining intraperitoneal administration of glucose alone (50-400 mg/kg) had no significant effect, while tacrine alone (0.5-3 mg/kg) improved avoidance acquisition at the dose of 2 mg/kg only. Significant avoidance learning improvements were instead produced by 50 or 100 mg/kg glucose combined with 0.5 or 1 mg/kg tacrine. The effects on shuttle-box avoidance acquisition produced by glucose combined with a cholinomimetic agent support the hypothesis that cholinergic mechanisms may be involved in the action of glucose on learning and memory. However, the main finding of the present study is related to the enhancement by glucose of the learning improving action of a drug clinically used as cognitive enhancer.

  10. Correlation between Salivary Glucose and Blood Glucose and the Implications of Salivary Factors on the Oral Health Status in Type 2 Diabetes Mellitus Patients

    PubMed Central

    Puttaswamy, Kavitha A.; Puttabudhi, Jaishankar H.; Raju, Shashidara

    2017-01-01

    Aims and Objectives: The purpose of this study was to estimate and assess any correlation between random capillary blood glucose (RCBG) and unstimulated whole salivary glucose (UWSG), as well as to estimate various salivary parameters, such as flow rate, pH, buffering capacity, and the influence of these factors on the oral health status in type 2 diabetes mellitus (DM). Materials and Methods: Sixty individuals suffering from type 2 DM and 40 healthy individuals in the age group of 30–60 years were included in the study. RCBG was estimated using glucometer and UWSG was estimated using photocolorimeter. Salivary parameters such as flow rate, pH, and buffering capacity were assessed using GC® Saliva kit. Oral health status was recorded using the Russell's periodontal index (RPI) and the Decayed Missing Filled Teeth (DMFT) index. The Statistical Package for the Social Sciences version 16 was used for statistical analysis. Results: Type 2 diabetics had higher mean values for RCBG levels and UWSG. Type 2 diabetics had low mean salivary flow rate, pH, and buffering capacity. Type 2 diabetics had higher mean values for RPI. Conclusion: Among the salivary factors studied, salivary glucose significantly influenced the periodontal status in Type 2 diabetics. PMID:28316946

  11. Comparison of the in-feed glucose test and the oral sugar test.

    PubMed

    Smith, S; Harris, P A; Menzies-Gow, N J

    2016-03-01

    The in-feed oral glucose test (OGT) and oral sugar test (OST) are advocated as field tests of insulin sensitivity in horses and ponies but have not been directly compared. To compare the insulin response to OGT and OST in 8 ponies and 5 horses of unknown insulin sensitivity. Experimental, randomised crossover study. Animals were fasted for 8 h overnight before and throughout testing. They were fed 1 g/kg bwt glucose powder with chaff (OGT) or 0.15 ml/kg bwt corn syrup (Karo™ Light Syrup; OST) was administered per os in a randomised crossover study with 48 h between tests. Blood samples were obtained at 0, 30, 60, 75, 90, 120 and 180 min. The maximal insulin concentration (Cmaxi ), time to maximal insulin concentration (Tmaxi ) and area under the curve of insulin concentration over time (AUCi ) for the tests were compared using Student's paired t test. The effect of individual subject, horse or pony and test were analysed using a linear mixed model. The OGT Cmaxi (mean ± s.d.; 154 ± 116 μiu/ml), Tmaxi (136 ± 52 min) and AUCi (15,308 ± 9886 μiu/ml/min) were significantly (P<0.05) greater compared with the OST Cmaxi (72 ± 55 μiu/ml), Tmaxi (63 ± 25 min) and AUCi (5980 ± 4151 μiu/ml/min). The Cmaxi , Tmaxi and AUCi varied significantly between individual subjects. The Tmaxi was significantly different between horses and ponies during OGT and OST. Using previously defined criteria of insulin dysregulation, OGT identified 7/13 animals as insulin resistant, whereas OST identified 5/13 animals as insulin resistant. The OGT and OST showed agreement in identification of insulin dysregulation in 85% of equine subjects. Results of the OGT and OST are not comparable in all cases. Further work is required to establish which test more accurately diagnoses insulin dysregulation in horses and ponies. © 2015 EVJ Ltd.

  12. Effects of three day bed-rest on circulatory, metabolic and hormonal responses to oral glucose load in endurance trained athletes and untrained subjects

    NASA Technical Reports Server (NTRS)

    Smorawinski, J.; Kubala, P.; Kaciuba-Uociako, H.; Nazar, K.; Titow-Stupnicka, E.; Greenleaf, J. E.

    1996-01-01

    Endurance trained long distance runners and untrained individuals underwent three days of bed rest and oral glucose loading. Before and after bed rest, individuals were given glucose tolerance tests, and their heart rates, blood pressure, blood glucose levels, insulin levels, and catecholamine interactions were measured. Results indicated that glucose tolerance is more affected by bed rest-induced deconditioning in untrained individuals than in trained individuals.

  13. Effects of three day bed-rest on circulatory, metabolic and hormonal responses to oral glucose load in endurance trained athletes and untrained subjects

    NASA Technical Reports Server (NTRS)

    Smorawinski, J.; Kubala, P.; Kaciuba-Uociako, H.; Nazar, K.; Titow-Stupnicka, E.; Greenleaf, J. E.

    1996-01-01

    Endurance trained long distance runners and untrained individuals underwent three days of bed rest and oral glucose loading. Before and after bed rest, individuals were given glucose tolerance tests, and their heart rates, blood pressure, blood glucose levels, insulin levels, and catecholamine interactions were measured. Results indicated that glucose tolerance is more affected by bed rest-induced deconditioning in untrained individuals than in trained individuals.

  14. A modified oral sugar test for evaluation of insulin and glucose dynamics in horses.

    PubMed

    Lindåse, Sanna; Nostell, Katarina; Bröjer, Johan

    2016-10-20

    An oral sugar test (OST) using Karo(®) Light Corn Syrup has been developed in the USA as a field test for the assessment of insulin dysregulation in horses but the syrup is not available in Scandinavian grocery stores. The aim of the study was to compare the results of a modified OST between horses with equine metabolic syndrome (EMS) and healthy horses using a Scandinavian commercially available glucose syrup (Dansukker glykossirap). In addition, the effect of breed and the repeatability of the test were evaluated. In the present study, clinically healthy horses (7 Shetland ponies, 8 Icelandic horses, 8 Standardbred horses) and 20 horses of various breeds with EMS underwent the modified OST test. The Icelandic horses and Shetland ponies underwent the OST twice. Insulin and glucose data from the OST were used to calculate peak insulin concentration (PeakINS), time to peak insulin concentration (T-peakINS), area under the curve for insulin (AUCINS) and glucose (AUCGLU) as well as whole body insulin sensitivity index (ISICOMP). Compared to the healthy group, the EMS group had 6-7 times higher geometric mean for PeakINS and AUCINS and 8 times lower geometric mean for ISICOMP. The EMS group had a delayed T-peakINS compared to the healthy group. There was no effect of breed in the group of healthy horses on PeakINS, T-peakINS, AUCINS, AUCGLU and ISICOMP. Coefficient of variation for repeated tests was 19.8, 19.0 and 17.6 % for PeakINS, AUCINS and ISICOMP respectively. The results of the present study demonstrate that the modified OST appears to be a practical and useful diagnostic tool for assessment of insulin dysregulation in the horse. However, to make it possible to establish the most appropriate sampling interval and to evaluate the accuracy of the modified OST, further studies in horses with a variable degree of insulin resistance are needed, where results from the modified OST are compared with quantitative measurements for IS.

  15. Lead, cadmium and aluminum in Canadian infant formulae, oral electrolytes and glucose solutions

    PubMed Central

    Dabeka, Robert; Fouquet, Andre; Belisle, Stephane; Turcotte, Stephane

    2011-01-01

    Lead (Pb), cadmium (Cd) and aluminum (Al) were determined in 437 individual samples of infant formulae, oral electrolytes and 5% glucose solutions available in Canada. In the electrolytes, Cd and Pb concentrations were all below 0.01 and 0.041 ng g−1, respectively. In the 5% glucose solutions, Pb and Cd levels averaged 0.01 and 0.09 ng g−1, respectively. Reported on an as-consumed basis, Pb levels in milk- and soya-based formulae averaged 0.90 and 1.45 ng g−1, respectively, while Cd levels averaged 0.23 and 1.18 ng g−1, respectively Average Al levels on an as-consumed basis were 440 ng g−1 (range 10–3400 ng g−1) in milk-based formulae and 730 ng g−1 (range 230–1100 ng g−1) in soy-based formulae. Al concentrations increased in the following order: plain formula < low-iron formula < iron-supplemented formula < casein hydrolysate formula ≈ premature formula ≤ soy formula. For example, in the powdered formulae, average Al concentrations were 18 ng g−1 for plain milk-based, 37 ng g−1 for low-iron, 128 ng g−1 for iron supplemented, 462 ng g−1 for lactose-free, 518 ng g−1 for hypoallergenic and 619 ng g−1 for soy-based formula. Al concentrations, as-consumed, increased with decreasing levels of concentration: powder < concentrated liquid < ready-to-use. Formulae stored in glass bottles contained between 100 and 300 ng g−1 more Al than the same formulae stored in cans. The source of the increased Al did not appear to be the glass itself, because most electrolytes and glucose solutions, also stored in glass, contained less than 8 ng g−1 Al. Corresponding differences in Pb and Cd levels were not observed. Al concentrations varied substantially among manufacturers; however, all manufacturers were able to produce plain milk-based formulae containing less than 50 ng g−1 Al, i.e. within the range of Al concentrations found in human milk. Next to soya-based and hypoallergenic formulae, premature formulae contained among the highest

  16. Lead, cadmium and aluminum in Canadian infant formulae, oral electrolytes and glucose solutions.

    PubMed

    Dabeka, Robert; Fouquet, Andre; Belisle, Stephane; Turcotte, Stephane

    2011-06-01

    Lead (Pb), cadmium (Cd) and aluminum (Al) were determined in 437 individual samples of infant formulae, oral electrolytes and 5% glucose solutions available in Canada. In the electrolytes, Cd and Pb concentrations were all below 0.01 and 0.041 ng g(-1), respectively. In the 5% glucose solutions, Pb and Cd levels averaged 0.01 and 0.09 ng g(-1), respectively. Reported on an as-consumed basis, Pb levels in milk- and soya-based formulae averaged 0.90 and 1.45 ng g(-1), respectively, while Cd levels averaged 0.23 and 1.18 ng g(-1), respectively Average Al levels on an as-consumed basis were 440 ng g(-1) (range 10-3400 ng g(-1)) in milk-based formulae and 730 ng g(-1) (range 230-1100 ng g(-1)) in soy-based formulae. Al concentrations increased in the following order: plain formula < low-iron formula < iron-supplemented formula < casein hydrolysate formula ≈ premature formula ≤ soy formula. For example, in the powdered formulae, average Al concentrations were 18 ng g(-1) for plain milk-based, 37 ng g(-1) for low-iron, 128 ng g(-1) for iron supplemented, 462 ng g(-1) for lactose-free, 518 ng g(-1) for hypoallergenic and 619 ng g(-1) for soy-based formula. Al concentrations, as-consumed, increased with decreasing levels of concentration: powder < concentrated liquid < ready-to-use. Formulae stored in glass bottles contained between 100 and 300 ng g(-1) more Al than the same formulae stored in cans. The source of the increased Al did not appear to be the glass itself, because most electrolytes and glucose solutions, also stored in glass, contained less than 8 ng g(-1) Al. Corresponding differences in Pb and Cd levels were not observed. Al concentrations varied substantially among manufacturers; however, all manufacturers were able to produce plain milk-based formulae containing less than 50 ng g(-1) Al, i.e. within the range of Al concentrations found in human milk. Next to soya-based and hypoallergenic formulae, premature formulae contained among the highest

  17. Pre-Type 1 Diabetes Dysmetabolism: Maximal sensitivity achieved with Both Oral and Intravenous Glucose Tolerance Testing

    PubMed Central

    Barker, Jennifer M.; McFann, Kim; Harrison, Leonard C.; Fourlanos, Spiros; Krischer, Jeffrey; Cuthbertson, David; Chase, H. Peter; Eisenbarth, George S.; Group, the DPT-1 Study

    2007-01-01

    Objective To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and identify an optimal testing strategy for detecting pre-clinical diabetes. Study design Diabetes Prevention Trial Type 1 randomized subjects to oral (n=372) and parenteral (n=339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. Results Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of FPIR at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline BMI, FPIR and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal first phase insulin response (FPIR) and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs. 73%). Conclusions Most (97%) subjects had abnormal IVGTTs and/or OGTTs prior to the development of diabetes. The highest sensitivity is achieved using both tests. PMID:17188609

  18. An acute oral dose of caffeine does not alter glucose kinetics during prolonged dynamic exercise in trained endurance athletes.

    PubMed

    Roy, B D; Bosman, M J; Tarnopolsky, M A

    2001-08-01

    This study investigated the possible influence of oral caffeine administration on endogenous glucose production and energy substrate metabolism during prolonged endurance exercise. Twelve trained endurance athletes [seven male, five female; peak oxygen consumption (VO2peak) = 65.5 ml.kg-1.min-1] performed 60 min of cycle ergometry at 65% VO2peak twice, once after oral caffeine administration (6 mg.kg-1) (CAF) and once following consumption of a placebo (PLA). CAF and PLA were administered in a randomized double-blind manner 75 min prior to exercise. Plasma glucose kinetics were determined with a primed-continuous infusion of [6,6-2H]glucose. No differences in oxygen consumption (VO2), and carbon dioxide production (VCO2) were observed between CAF and PLA, at rest or during exercise. Blood glucose concentrations were similar between the two conditions at rest and also during exercise. Exercise did lead to an increase in serum free fatty acid (FFA) concentrations for both conditions; however, no differences were observed between CAF and PLA. Both the plasma glucose rate of appearance (Ra) and disappearance (Rd) increased at the onset of exercise (P < 0.05), but were not affected by CAF, as compared to PLA. CAF did lead to a higher plasma lactate concentration during exercise (P < 0.05). It was concluded that an acute oral dose of caffeine does not influence plasma glucose kinetics or energy substrate oxidation during prolonged exercise in trained endurance athletes. However, CAF did lead to elevated plasma lactate concentrations. The exact mechanism of the increase in plasma lactate concentrations remains to be determined.

  19. Oral green tea catechins transiently lower plasma glucose concentrations in female db/db mice.

    PubMed

    Wein, Silvia; Schrader, Eva; Rimbach, Gerald; Wolffram, Siegfried

    2013-04-01

    Polyphenols, including green tea catechins, are secondary plant compounds often discussed in the context of health-promoting potential. Evidence for such effects is mainly derived from epidemiological and cell culture studies. The aim of the present study was to investigate antidiabetic, antiadipogenic, and anti-inflammatory effects at nonpharmacological doses in an obese diabetic mouse model that exerts early relevant clinical signs of non-insulin-dependent diabetes mellitus. Female db/db mice received a flavonoid-poor diet either without additive, with rosiglitazone (RSG, 0.02 g/kg diet), or with green tea extract (low-dose green tea extract [LGTE] and high-dose green tea extract [HGTE], 0.1 and 1 g/kg diet). Food and water were freely available. The body weight was monitored weekly. Blood was sampled (12-h fasted) from the tail vein on day 28 and analyzed for glucose, cholesterol, triacylglycerol, nonesterified fatty acids, insulin, adiponectin, and soluble intercellular adhesion molecule-1 (sICAM-1). Blood glucose was also analyzed on day 14. Furthermore, sICAM-1 release was investigated in tumor necrosis factor alpha-stimulated EAhy926 cells. After 14 days, fasting glycemia was improved by RSG or HGTE supplementation compared to controls. However, at the end of the study (day 28), only RSG exhibited glucose-lowering effects and induced plasma adiponectin concentrations, paralleled by higher body weight gain and reduced periuterine fat pads compared to controls. However, only GTE treatment reduced sICAM-1 release in vitro and in vivo. Nonpharmacological HGTE supplementation in db/db mice caused (1) no adiponectin-inducing or antiadipogenic effects, (2) reduced sICAM-1 release, thereby potentially exerting anti-inflammatory effects in the progressive diabetic state, and (3) a transient improvement in glycemia.

  20. Workforce strategies to improve children's oral health.

    PubMed

    Goodwin, Kristine

    2014-12-01

    (1) Tooth decay is the most common chronic disease for children. (2) As millions receive dental coverage under the Affordable Care Act, the demand for dental services is expected to strain the current workforce's ability to meet their needs. (3) States have adopted various workforce approaches to improve access to dental care for underserved populations.

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

    PubMed

    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

    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. 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. 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. 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.

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

    PubMed Central

    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

  3. Initial choice of oral glucose-lowering medication for diabetes mellitus: a patient-centered comparative effectiveness study.

    PubMed

    Berkowitz, Seth A; Krumme, Alexis A; Avorn, Jerry; Brennan, Troyen; Matlin, Olga S; Spettell, Claire M; Pezalla, Edmund J; Brill, Gregory; Shrank, William H; Choudhry, Niteesh K

    2014-12-01

    Although many classes of oral glucose-lowering medications have been approved for use, little comparative effectiveness evidence exists to guide initial selection of therapy for diabetes mellitus. To determine the effect of initial oral glucose-lowering agent class on subsequent need for treatment intensification and 4 short-term adverse clinical events. This study was a retrospective cohort study of patients who were fully insured members of Aetna (a large national health insurer) who had been prescribed an oral glucose-lowering medication from July 1, 2009, through June 30, 2013. Individuals newly prescribed an oral glucose-lowering agent who filled a second prescription for a medication in the same class and with a dosage at or above the World Health Organization's defined daily dose within 90 days of the end-of-day's supply of the first prescription were studied. Individuals with interim prescriptions for other oral glucose-lowering medications were excluded. Initiation of treatment with metformin, a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor. Time to addition of a second oral agent or insulin, each component separately, hypoglycemia, other diabetes-related emergency department visits, and cardiovascular events. A total of 15 516 patients met the inclusion criteria, of whom 8964 (57.8%) started therapy with metformin. In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P < .001 for all). In propensity score and multivariable-adjusted Cox proportional hazards models, initiation of therapy with sulfonylureas (hazard ratio [HR], 1.68; 95% CI, 1.57-1.79), thiazolidinediones (HR, 1.61; 95% CI, 1.43-1.80), and dipeptidyl peptidase 4 inhibitors (HR, 1.62; 95% CI, 1.47-1.79) was associated with an increased hazard of intensification. Alternatives to metformin were not associated with a

  4. Effects of a single bout of aerobic exercise on short-term low-carbohydrate/high-fat intake-induced postprandial glucose metabolism during an oral glucose tolerance test.

    PubMed

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Konishi, Masayuki; Takahashi, Masaki; Sakamoto, Shizuo

    2013-10-01

    A single bout of exercise can improve acute postprandial glucose metabolism aggravated by short-term low-carbohydrate/high-fat diet (HFD). The purpose of this study was to investigate the effect of a single bout of aerobic exercise on short-term HFD-induced postprandial glucose and incretin metabolism during an oral glucose tolerance test (OGTT). Eleven healthy young men (age [mean±SE] 27±1 years; body mass index, 22±1 kg/m(2)) performed three, 3-day interventions in randomized order: (1) a normal diet (ND: ~22% fat), (2) an HFD (~69% fat) and (3) an HFD with a single bout of aerobic exercise (HFDEx). The exercise (50% peak oxygen consumption; ~200 kcal) was performed on the third day in HFDEx. An OGTT was performed after each 3-day dietary intervention. The incremental area under the curve (iAUC) of plasma glucose levels during the OGTT was significantly higher in the HFD and HFDEx trials than in the ND trial (P=0.001). In addition, the iAUC of glucagon-like peptide-1 (GLP-1) level was significantly higher in the HFD trial than in the ND and HFDEx trials (P=0.04). The first-phase insulin secretion indexes were significantly lower in the HFD (P=0.01 and 0.002) and HFDEx trials (P=0.05 and 0.008) than in the ND trial. A single bout of aerobic exercise did not improve the short-term HFD-induced aggravation of postprandial glucose and insulin metabolism during the OGTT. However, it did normalize the increased postprandial GLP-1 level induced by HFD. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.

    PubMed

    Amitani, Haruka; Asakawa, Akihiro; Cheng, Kaichun; Amitani, Marie; Kaimoto, Kaori; Nakano, Masako; Ushikai, Miharu; Li, Yingxiao; Tsai, Minglun; Li, Jiang-Bo; Terashi, Mutsumi; Chaolu, Huhe; Kamimura, Ryozo; Inui, Akio

    2013-01-01

    Hydrogen (H(2)) acts as a therapeutic antioxidant. However, there are few reports on H(2) function in other capacities in diabetes mellitus (DM). Therefore, in this study, we investigated the role of H(2) in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2) promoted 2-[(14)C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2) significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p.) and oral (p.o.) administration. However, long-term p.o. administration of H(2) had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2) exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

  6. Polyphenol-rich Rutgers Scarlet Lettuce improves glucose metabolism and liver lipid accumulation in diet-induced obese C57BL/6 mice.

    PubMed

    Cheng, Diana M; Pogrebnyak, Natalia; Kuhn, Peter; Poulev, Alexander; Waterman, Carrie; Rojas-Silva, Patricio; Johnson, William D; Raskin, Ilya

    2014-01-01

    The aims of the following experiments were to characterize antidiabetic in vitro and in vivo activity of the polyphenol-rich aqueous extract of Rutgers Scarlet Lettuce (RSL). RSL extract (RSLE) and isolated compounds were evaluated for inhibitory effects on glucose production as well as tumor necrosis factor alpha-dependent inhibition of insulin activity in H4IIE rat hepatoma cells. Additionally, high-fat diet-induced obese mice were treated with RSLE (100 or 300 mg/kg), metformin (250 mg/kg), or vehicle (water) for 28 d by oral administration and insulin and oral glucose tolerance tests were conducted. Tissues were harvested at the end of the study and evaluated for biochemical and physiological improvements in metabolic syndrome conditions. A polyphenol-rich RSLE, containing chlorogenic acid, cyanidin malonyl-glucoside, and quercetin malonyl-glucoside, was produced by simple boiling water extraction at pH 2.0. In vitro, RSLE and chlorogenic acid demonstrated dose-dependent inhibition of glucose production. In vivo, RSLE treatment improved glucose metabolism measured by oral glucose tolerance tests, but not insulin tolerance tests. RSLE treated groups had a lower ratio of liver weight to body weight as well as decreased total liver lipids compared with the control group after 28 d of treatment. No significant differences in plasma glucose, insulin, cholesterol, and triglycerides were observed with RSLE-treated groups compared with vehicle control. RSLE demonstrated antidiabetic effects in vitro and in vivo and may improve metabolic syndrome conditions of fatty liver and glucose metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Polyphenol-Rich Rutgers Scarlet Lettuce Improves Glucose Metabolism and Liver Lipid Accumulation in Diet Induced Obese C57BL/6 Mice

    PubMed Central

    Cheng, Diana M.; Pogrebnyak, Natalia; Kuhn, Peter; Poulev, Alexander; Waterman, Carrie; Rojas-Silva, Patricio; Johnson, William D.

    2014-01-01

    Objective The aims of the following experiments were to characterize anti-diabetic in vitro and in vivo activity of the polyphenol-rich aqueous extract of Rutgers Scarlet Lettuce. Materials / Methods Rutgers Scarlet Lettuce (RSL) extract (RSLE) and isolated compounds were evaluated for inhibitory effects on glucose production as well as tumor necrosis factor alpha (TNFα)-dependent inhibition of insulin activity in H4IIE rat hepatoma cells. Additionally, high fat diet-induced obese mice were treated with RSLE (100 or 300 mg/kg), Metformin (250 mg/kg) or vehicle (water) for 28 days by oral administration and insulin and oral glucose tolerance tests were conducted. Tissues were harvested at the end of the study and evaluated for biochemical and physiological improvements in metabolic syndrome conditions. Results A polyphenol-rich RSLE, containing chlorogenic acid, cyanidin malonyl-glucoside and quercetin malonyl-glucoside, was produced by simple boiling water extraction at pH 2. In vitro, RSLE and chlorogenic acid demonstrated dose-dependent inhibition of glucose production. In vivo, RSLE treatment improved glucose metabolism measured by oral glucose tolerance tests, but not insulin tolerance tests. RSLE treated groups had a lower ratio of liver weight to body weight as well as decreased total liver lipids compared to control group after 28 days of treatment. No significant differences in plasma glucose, insulin, cholesterol, and triglycerides were observed with RSLE treated groups compared to vehicle control. Conclusion RSLE demonstrated anti-diabetic effects in vitro and in vivo and may improve metabolic syndrome conditions of fatty liver and glucose metabolism. PMID:24985107

  8. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria

    PubMed Central

    Adams, Jessica M.; Fagel, Brian; Lam, Daniel D.; Qi, Nathan; Rubinstein, Marcelo

    2016-01-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium–glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  9. Improving oral healthcare delivery systems through workforce innovations: an introduction.

    PubMed

    Mertz, Elizabeth A; Finocchio, Len

    2010-06-01

    The objective of this paper is to describe the purpose, rationale and key elements of the special issue, Improving Oral Healthcare Delivery Systems through Workforce Innovations. The purpose of the special issue is to further develop ideas presented at the 2009 Institute of Medicine (IOM) workshop, Sufficiency of the U.S. Oral Health Workforce in the Coming Decade. Using the IOM discussions as their starting point, the authors evaluate oral health care delivery system performance for specific populations' needs and explore the roles that the workforce can play in improving the care delivery model. The contributing articles provide a broad framework for stimulating and evaluating innovation and change in the oral health care delivery system. The articles in this special issue point to many deficits in the current oral health care delivery system and provide compelling arguments and proposals for improvements. The issues presented and solutions recommended are not entirely new, but add to a growing body of work that is of critical importance given the context of wider health care reform.

  10. Dietary Capsaicin Improves Glucose Homeostasis and Alters the Gut Microbiota in Obese Diabetic ob/ob Mice.

    PubMed

    Song, Jun-Xian; Ren, Hui; Gao, Yuan-Feng; Lee, Chong-You; Li, Su-Fang; Zhang, Feng; Li, Long; Chen, Hong

    2017-01-01

    Background: The effects of capsaicin on obesity and glucose homeostasis are still controversial and the mechanisms underlying these effects remain largely unknown. This study aimed to investigate the potential relationship between the regulation of obesity and glucose homeostasis by dietary capsaicin and the alterations of gut microbiota in obese diabetic ob/ob mice. Methods: The ob/ob mice were subjected to a normal, low-capsaicin (0.01%), or high-capsaicin (0.02%) diet for 6 weeks, respectively. Obesity phenotypes, glucose homeostasis, the gut microbiota structure and composition, short-chain fatty acids, gastrointestinal hormones, and pro-inflammatory cytokines were measured. Results: Both the low- and high-capsaicin diets failed to prevent the increase in body weight, adiposity index, and Lee's obesity index. However, dietary capsaicin at both the low and high doses significantly inhibited the increase of fasting blood glucose and insulin levels. These inhibitory effects were comparable between the two groups. Similarly, dietary capsaicin resulted in remarkable improvement in glucose and insulin tolerance. In addition, neither the low- nor high-capsaicin diet could alter the α-diversity and β-diversity of the gut microbiota. Taxonomy-based analysis showed that both the low- and high-capsaicin diets, acting in similar ways, significantly increased the Firmicutes/Bacteroidetes ratio at the phylum level as well as increased the Roseburia abundance and decreased the Bacteroides and Parabacteroides abundances at the genus level. Spearman's correlation analysis revealed that the Roseburia abundance was negatively while the Bacteroides and Parabacteroides abundances were positively correlated to the fasting blood glucose level and area under the curve by the oral glucose tolerance test. Finally, the low- and high-capsaicin diets significantly increased the fecal butyrate and plasma total GLP-1 levels, but decreased plasma total ghrelin, TNF-α, IL-1β, and IL-6

  11. Does oral glutamine improve insulin sensitivity in adolescents with type 1 diabetes?

    PubMed

    Torres-Santiago, Lournaris; Mauras, Nelly; Hossain, Jobayer; Weltman, Arthur L; Darmaun, Dominique

    2017-02-01

    The decline in insulin sensitivity (SI) associated with puberty increases the difficulty of achieving glycemic control in adolescents with type 1 diabetes (T1D). The aim of this study was to determine whether glutamine supplementation affects blood glucose by enhancing SI in adolescents with T1D. Thirteen adolescents with T1D (HbA1C 8.2 ± 0.1%) were admitted to perform afternoon exercise (four 15-min treadmill/5-min rest cycles of exercise) on two occasions within a 4-wk period. They were randomized to receive a drink containing either glutamine (0.25 g/kg) or placebo before exercise, at bedtime, and early morning in a double-blind, crossover design. Blood glucose was monitored overnight, and a hyperinsulinemic-euglycemic clamp was performed the following morning. Blood glucose concentration dropped comparably during exercise on both days. However, the total number of nocturnal hypoglycemic events (17 versus 7, P = 0.045) and the cumulative probability of overnight hypoglycemia (50% versus 33%, P = 0.02) were higher on the glutamine day than on the placebo day. During clamp, glucose infusion rate was not affected by glutamine supplementation (7.7 ± 1 mg • kg(-1) • min(-1) versus 7.0 ± 1; glutamine versus placebo; P = 0.4). Oral glutamine supplementation decreases blood glucose in adolescents with T1D after exercise. Insulin sensitivity, however, was unaltered during the euglycemic clamp. Although the mechanisms involved remain to be elucidated, studies to explore the potential use of glutamine to improve blood glucose control are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Hypothalamic vitamin D improves glucose homeostasis and reduces weight

    USDA-ARS?s Scientific Manuscript database

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weigh...

  13. Glyceollins, soy isoflavone phytoalexins, improve oral glucose disposal by stimulating glucose uptake

    USDA-ARS?s Scientific Manuscript database

    Glyceollins (glyceollin I, II, and III), isoflavone phytoalexins synthesized by soy in response to environmental stresses such as microbial infections. Glyceollins exhibited anti-cancer and anti-diabetes effects: previously we showed that glyceollins inhibited cancer cell growth in vitro and in viv...

  14. Berberine improves glucose metabolism through induction of glycolysis.

    PubMed

    Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping

    2008-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for > or =16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio.

  15. Effectiveness of Medium-Chain Triglyceride Oil Therapy in Two Japanese Citrin-Deficient Siblings: Evaluation Using Oral Glucose Tolerance Tests.

    PubMed

    Otsuka, Hiroki; Sasai, Hideo; Abdelkreem, Elsayed; Kawamoto, Norio; Kawamoto, Minako; Kamiya, Toshiya; Tanimoto, Yasuo; Kikuchi, Atsuo; Kure, Shigeo; Numakura, Chikahiko; Hayasaka, Kiyoshi; Fukao, Toshiyuki

    2016-12-01

    Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD(+) ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis. The brother and sister underwent an oral glucose tolerance test (OGTT) at 10 and 7 yr of age, respectively. Blood glucose, ammonia, lactic acid, pyruvic acid, and insulin levels were monitored before starting the test, and then every 30 min. During this test, they maintained blood glucose levels until 180 min. At 210 min, they experienced vomiting, feeling ill, and decreased blood glucose levels (2.9 and 2.8 mmol/l in the brother and sister, respectively). The sister and brother recovered uneventfully by intravenous glucose injection. In a second OGTT, 4 months after medium-chain triglyceride (MCT) oil supplementation, they had no major symptoms and normal glucose levels were maintained, even after 240 min. Additionally, after MCT oil therapy, their food preference slightly changed as they started eating more carbohydrates. Our OGTT data suggest excess carbohydrate intake has adverse consequences in patients with citrin deficiency, including hypoglycemia after a few hours. MCT oil therapy may be effective in preventing such hypoglycemia and improving metabolic derangement, even during the so-called apparently healthy period.

  16. Development and assessment of the disposition index based on the oral glucose tolerance test in subjects with different glycaemic status.

    PubMed

    Santos, J L; Yévenes, I; Cataldo, L R; Morales, M; Galgani, J; Arancibia, C; Vega, J; Olmos, P; Flores, M; Valderas, J P; Pollak, F

    2016-06-01

    Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.

  17. Rosiglitazone fails to improve hypertriglyceridemia and glucose tolerance in CD36-deficient BN.SHR4 congenic rat strain.

    PubMed

    Seda, Ondrej; Kazdova, Ludmila; Krenova, Drahomira; Kren, Vladimir

    2003-01-15

    The favorable metabolic effects of thiazolidinediones are supposedly related to the peroxisome proliferator-activated receptor-gamma (PPARgamma)-driven changes in lipid metabolism, particularly in free fatty acid (FFA) trafficking. The fatty acid translocase CD36 is one of the proposed PPARgamma targets to mediate this action. We assessed the effect of rosiglitazone (RSG, Avandia) administration in two inbred rat strains, BN/Cub and BN.SHR4 congenic strain, differing in 10 cM proximal segment of chromosome 4. Rats were fed high-sucrose diet with or without RSG for 1 wk. In BN.SHR4, which carries defective Cd36 allele of SHR origin, RSG failed to improve glucose tolerance (assessed by the oral glucose tolerance test), did not lower triglyceridemia, nor induced increases in epididymal and retroperitoneal adipose tissue weights and adipose tissue glucose utilization, effects observed in BN/Cub. On the other hand, the RSG-treated BN.SHR4 showed lower concentrations of FFA and substantial increase in glycogen synthesis and glucose oxidation in skeletal muscle. Altogether, these results support involvement of CD36 in RSG action, suggesting this pharmacogenetic interaction may be of particular importance in CD36-deficient humans.

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  19. FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1.

    PubMed

    Kwon, Michelle M; O'Dwyer, Shannon M; Baker, Robert K; Covey, Scott D; Kieffer, Timothy J

    2015-11-24

    Fibroblast growth factor 21 (FGF21)-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1) levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT) temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  1. Periodontal Bacteria and Prediabetes Prevalence in ORIGINS: The Oral Infections, Glucose Intolerance, and Insulin Resistance Study.

    PubMed

    Demmer, R T; Jacobs, D R; Singh, R; Zuk, A; Rosenbaum, M; Papapanou, P N; Desvarieux, M

    2015-09-01

    Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P

  2. Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load.

    PubMed

    Krusenstjerna-Hafstrøm, Thomas; Madsen, Michael; Vendelbo, Mikkel H; Pedersen, Steen B; Christiansen, Jens S; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

    2011-05-03

    GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load. Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1) after an intravenous GH bolus 2) after an intravenous GH bolus plus an oral glucose load (OGTT), and 3) after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA). GH increased AUC(glucose) after an OGTT (p<0.05) without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473) and thr(308)), and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1) A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2) Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3) The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH. ClinicalTrials.gov NCT00477997.

  3. Overexpression of p53 Improves Blood Glucose Control in an Insulin Resistant Diabetic Mouse Model.

    PubMed

    Zhang, Xuemei; Duan, Wei; Lee, Wai-Nang Paul; Zhang, Yuewei; Xiang, Fenfen; Liu, Qian; Go, Vay Liang W; Xiao, Gary Guishan

    2016-08-01

    This paper aimed to assess the physiological effects of p53 on glucose homeostasis in vivo. A recombinant adenoviral p53 (rAd-p53) vector was administered to insulin-resistant diabetic mice. Intraperitoneal glucose tolerance test was performed in all groups of mice. Changes in fasting blood glucose, serum triglycerides, C-peptide, and insulin concentrations in treated and untreated mice were measured. Analyses of the target genes related to glucose metabolism were performed. Treatment with the rAd-p53 improved glucose control in a dose- and time-dependent manner and lowered significantly the fasting blood glucose, the serum triglycerides, and improved tolerance test of glucose as compared to control. Lowered blood glucose was associated with up-regulation of genes in the glycogenesis pathways, and down-regulation of genes in the gluconeogenesis pathways in the liver. Overexpressions of GLUT2, GK, PPAR-γ, and insulin receptor precursor were also observed in the liver and the pancreas of treated animals. Activation of p53-mediated glucose metabolism led to insulin-like antidiabetic effect in the mouse model especially by changing hepatic insulin sensitivity in the diabetic mouse model.

  4. Native fructose extracted from apple improves glucose tolerance in mice.

    PubMed

    Dray, C; Colom, A; Guigné, C; Legonidec, S; Guibert, A; Ouarne, F; Valet, P

    2009-12-01

    Fructose is one of the most abundant monosaccharide in nature. It is also the sweetest naturally occurring carbohydrate. Since decades, fructose used for food preparations is not provided by fruit or vegetable but by a chemical process of starch or inulin conversion. We processed a new method of fructose extraction from apple and investigated the acute and long term effect of this carbohydrate on glucose metabolism in C57Bl6/j mice. By using the glycemic index (GI), we have shown that one of the sugars obtained from apple, FructiLight, has a very low impact on glycemic and insulin response during acute treatment compared to other sugars. This carbohydrate, essentially constituted by fructose, has also beneficial properties when administrated for long term treatment. Indeed, as two other sugars extracted from apple (FructiSweetApple and FructiSweet67), FructiLight exposure during 21 weeks in beverage has promoted an enhancement of glucose tolerance compared to glucose treatment without affecting food intake and weight. All these results indicate that apple-extracted sugars and more precisely fructose from these fruits could be a promising way to produce new food and sweet beverages.

  5. Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats

    PubMed Central

    Lin, Wenting; Wang, Wenxiang; Liao, Dongdong; Chen, Damiao; Zhu, Pingping; Cai, Guoxi; Kiyoshi, Aoyagi

    2015-01-01

    This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet β-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM. PMID:26347892

  6. [An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

    PubMed

    Sakaguchi, Hideo

    2014-06-01

    Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33 males, 69 females, mean age: 76.9 +/- 5.7) considered to be in potential need of long-term social care and attending a long-term care prevention class in Sayama City, Saitama Prefecture, Japan. The degree of improvement in oral functions (7 items) and oral hygienic conditions (3 items) was assessed by comparing oral health before and after participation in the program. The results showed statistically significant improvements in the following oral functions: (1) lip functions (oral diadochokinesis, measured by the regularity of the repetition of the syllable "Pa"), (2) tongue functions, (3) tongue root motor skills (oral diadochokinesis, measured by the regularity of the repetition of the syllables "Ta" and "Ka"), (4) tongue extension/retraction, (5) side-to-side tongue movement functions, (6) cheek motor skills, and (7) repetitive saliva swallowing test (RSST). The following measures of oral hygiene also showed a statistically significant improvement: (1) debris on dentures or teeth, (2) coated tongue, and (3) frequency of oral cleaning. These findings demonstrated that an improvement program informed by health behavior theories is useful in improving oral functions and oral hygiene conditions.

  7. Oral glucose tolerance test for preoperative assessment of liver function in liver resection

    PubMed Central

    Rachapoodivenkata, Raghavendra Rao

    2017-01-01

    Backgrounds/Aims We intended to determine the role of the Oral glucose tolerance test (OGTT), in addition to volumetry, in preoperative assessment of patients undergoing liver resection. Methods This was a prospective study conducted at a tertiary care hospital, between February 2009 and February 2011. OGTT curve (parabolic/linear), linearity index (LI) and Parenchymal Hepatic Resection Rate (PHRR) were correlated with postoperative outcomes in terms of postoperative liver failure (PLF), by 50-50 criteria, morbidity, mortality and hospital stay. Results Of the 33 patients included in the study, 23 (69.7%) patients underwent major liver resections. Hepatocellular carcinoma (30.3%) was the leading indication. The overall postoperative morbidity rate was 72.7%, but major complications occurred in 3 (9.1%) patients only. There was no 90-day mortality. The 50-50 criteria were met by 3 patients undergoing major resection. Significant correlation was noted between the linear OGTT curve and the overall hospital stay (12.1 days vs. 9.6 days in parabolic; p=0.04). Patients with linear OGTT met the 50-50 criteria more often (18%) than those having a parabolic curve (4.5%; p=0.25). Although the OGTT was more often linear with occurrence of morbidity (41.7% vs 11.1%), major morbidity (66.7% vs 30%) and PLF by 50-50 criteria (66.7% vs 30%), it was not statistically significant. The linearity index was marginally lower (0.9 vs 1.2) in the presence of major morbidity and PLF by 50-50 criteria. Conclusions Linear OGTT affects the PLF and major morbidity, therein impacting the hospital stay. OGTT LI and PHRR can help predict postoperative outcome for a given extent of liver resection. PMID:28317039

  8. Glucose improves object-location binding in visual-spatial working memory.

    PubMed

    Stollery, Brian; Christian, Leonie

    2016-02-01

    There is evidence that glucose temporarily enhances cognition and that processes dependent on the hippocampus may be particularly sensitive. As the hippocampus plays a key role in binding processes, we examined the influence of glucose on memory for object-location bindings. This study aims to study how glucose modifies performance on an object-location memory task, a task that draws heavily on hippocampal function. Thirty-one participants received 30 g glucose or placebo in a single 1-h session. After seeing between 3 and 10 objects (words or shapes) at different locations in a 9 × 9 matrix, participants attempted to immediately reproduce the display on a blank 9 × 9 matrix. Blood glucose was measured before drink ingestion, mid-way through the session, and at the end of the session. Glucose significantly improves object-location binding (d = 1.08) and location memory (d = 0.83), but not object memory (d = 0.51). Increasing working memory load impairs object memory and object-location binding, and word-location binding is more successful than shape-location binding, but the glucose improvement is robust across all difficulty manipulations. Within the glucose group, higher levels of circulating glucose are correlated with better binding memory and remembering the locations of successfully recalled objects. The glucose improvements identified are consistent with a facilitative impact on hippocampal function. The findings are discussed in the context of the relationship between cognitive processes, hippocampal function, and the implications for glucose's mode of action.

  9. Assessment of incretins in oral glucose and lipid tolerance tests may be indicative in the diagnosis of metabolic syndrome aggravation.

    PubMed

    Kiec-Klimczak, M; Malczewska-Malec, M; Razny, U; Zdzienicka, A; Gruca, A; Goralska, J; Pach, D; Gilis-Januszewska, A; Dembinska-Kiec, A; Hubalewska-Dydejczyk, A

    2016-04-01

    Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P < 0.001) within each of the investigated groups. In patients with the highest fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin

  10. Vertical sleeve gastrectomy improves glucose and lipid metabolism and delays diabetes onset in UCD-T2DM rats.

    PubMed

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber L; Kowala, Mark; Haj, Fawaz G; Chouinard, Michael L; Havel, Peter J

    2012-08-01

    Vertical sleeve gastrectomy (VSG) has gained interest as a low morbidity bariatric surgery, which is effective in producing weight loss and causing type 2 diabetes resolution. However, the efficacy of VSG to prevent the onset of type 2 diabetes has not been previously investigated. VSG or sham surgery was performed on 2-month-old prediabetic male University of California Davis-type 2 diabetes mellitus rats. Sham-operated animals were either sham-operated ad libitum fed (S-AL) or were weight-matched to VSG-operated animals (S-WM). Diabetes onset was determined by weekly nonfasting blood glucose measurements. Animals underwent oral glucose tolerance tests at 1 and 4 months after surgery and indirect calorimetry at 1.5 months after surgery. VSG surgery significantly delayed diabetes onset compared with both S-AL and S-WM animals. VSG-operated animals ate 23% less and weighed 20% less than S-AL. Energy expenditure did not differ between VSG-operated animals and controls. Results from the oral glucose tolerance tests demonstrate improved glucose tolerance and islet function in VSG-operated animals compared with S-AL and S-WM. Nutrient-stimulated glucagon-like peptide (GLP)-1, GLP-2, and peptide YY excursions were greater in VSG-operated animals. VSG surgery resulted in decreased fasting plasma insulin, ghrelin and lipid concentrations, and markedly higher fasting plasma adiponectin and bile acid concentrations, independent of body weight. Increases of circulating bile acid concentrations were due to selective increases of taurine-conjugated bile acids. Thus, VSG delays type 2 diabetes onset in the University of California Davis-type 2 diabetes mellitus rat, independent of body weight. This is potentially mediated by increases of circulating bile acids, adiponectin, and nutrient-stimulated GLP-1 secretion and decreased circulating ghrelin concentrations.

  11. Sourdough-leavened bread improves postprandial glucose and insulin plasma levels in subjects with impaired glucose tolerance.

    PubMed

    Maioli, Mario; Pes, Giovanni Mario; Sanna, Manuela; Cherchi, Sara; Dettori, Mariella; Manca, Elena; Farris, Giovanni Antonio

    2008-06-01

    Sourdough bread has been reported to improve glucose metabolism in healthy subjects. In this study postprandial glycaemic and insulinaemic responses were evaluated in subjects with impaired glucose tolerance (IGT) who had a meal containing sourdough bread leavened with lactobacilli, in comparison to a reference meal containing bread leavened with baker yeast. Sixteen IGT subjects (age range 52-75, average BMI 29.9 +/- 4.2 kg/ m2) were randomly given a meal containing sourdough bread (A) and a meal containing the reference bread (B) in two separate occasions at the beginning of the study and after 7 days. Sourdough bread was leavened for 8 h using a starter containing autochthonous Saccharomyces cerevisiae and several bacilli able to produce a significant amount of D-and L-lactic acid, whereas the reference bread was leavened for 2 h with commercial baker yeast containing Saccharomyces cerevisiae. Plasma glucose and insulin levels were measured at time 0, 30, 60, 120, and 180 min. In IGT subjects sourdough bread induced a significantly lower plasma glucose response at 30 minutes (p = 0.048) and a smaller incremental area under curve (AUC) delta 0-30 and delta 0-60 min (p = 0.020 and 0.018 respectively) in comparison to the bread leavened with baker yeast. Plasma insulin response to this type of bread showed lower values at 30 min (p = 0.045) and a smaller AUC delta 0-30 min (p = 0.018). This study shows that in subjects with IGT glycaemic and insulinaemic responses after the consumption of sourdough bread are lower than after the bread leavened with baker yeast. This effect is likely due to the lactic acid produced during dough leavening as well as the reduced availability of simple carbohydrates. Thus, sour-dough bread may potentially be of benefit in subjects with impaired glucose metabolism.

  12. Glycemic variability in relation to oral disposition index in the subjects with different stages of glucose tolerance.

    PubMed

    Chen, Tong; Xu, Feng; Su, Jian-Bin; Wang, Xue-Qin; Chen, Jin-Feng; Wu, Gang; Jin, Yan; Wang, Xiao-Hua

    2013-01-01

    Glucose variability could be an independent risk factor for diabetes complications in addition to average glucose. The deficiency in islet β cell secretion and insulin sensitivity, the two important pathophysiological mechanisms of diabetes, are responsible for glycemic disorders. The oral disposition index evaluated by product of insulin secretion and sensitivity is a useful marker of islet β cell function. The aim of the study is to investigate glycemic variability in relation to oral disposition index in the subjects across a range of glucose tolerance from the normal to overt type 2 diabetes. 75-g oral glucose tolerance test (OGTT) was performed in total 220 subjects: 47 with normal glucose regulation (NGR), 52 with impaired glucose metabolism (IGM, 8 with isolated impaired fasting glucose [IFG], 18 with isolated impaired glucose tolerance [IGT] and 26 with combined IFG and IGT), 61 screen-diagnosed diabetes by isolated 2-h glucose (DM2h) and 60 newly diagnosed diabetes by both fasting and 2-h glucose (DM). Insulin sensitivity index (Matsuda index, ISI), insulin secretion index (ΔI30/ΔG30), and integrated β cell function measured by the oral disposition index (ΔI30/ΔG30 multiplied by the ISI) were derived from OGTT. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SD), mean of blood glucose (MBG), high blood glucose index (HBGI), continuous overlapping net glycemic action calculated every 1 h (CONGA1), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE). From the NGR to IGM to DM2h to DM group, the respective values of SD (mean ± SD) (0.9 ± 0.3, 1.5 ± 0.5, 1.9 ± 0.6 and 2.2 ± 0.6 mmol/), MBG (5.9 ± 0.5, 6.7 ± 0.7, 7.7 ± 1.0 and 8.7 ± 1.5 mmol/L), HGBI [median(Q1-Q3)][0.8(0.2-1.2), 2.0(1.2-3.7), 3.8(2.4-5.6) and 6

  13. Glycemic variability in relation to oral disposition index in the subjects with different stages of glucose tolerance

    PubMed Central

    2013-01-01

    Background Glucose variability could be an independent risk factor for diabetes complications in addition to average glucose. The deficiency in islet β cell secretion and insulin sensitivity, the two important pathophysiological mechanisms of diabetes, are responsible for glycemic disorders. The oral disposition index evaluated by product of insulin secretion and sensitivity is a useful marker of islet β cell function. The aim of the study is to investigate glycemic variability in relation to oral disposition index in the subjects across a range of glucose tolerance from the normal to overt type 2 diabetes. Methods 75-g oral glucose tolerance test (OGTT) was performed in total 220 subjects: 47 with normal glucose regulation (NGR), 52 with impaired glucose metabolism (IGM, 8 with isolated impaired fasting glucose [IFG], 18 with isolated impaired glucose tolerance [IGT] and 26 with combined IFG and IGT), 61 screen-diagnosed diabetes by isolated 2-h glucose (DM2h) and 60 newly diagnosed diabetes by both fasting and 2-h glucose (DM). Insulin sensitivity index (Matsuda index, ISI), insulin secretion index (ΔI30/ΔG30), and integrated β cell function measured by the oral disposition index (ΔI30/ΔG30 multiplied by the ISI) were derived from OGTT. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SD), mean of blood glucose (MBG), high blood glucose index (HBGI), continuous overlapping net glycemic action calculated every 1 h (CONGA1), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE). Results From the NGR to IGM to DM2h to DM group, the respective values of SD (mean ± SD) (0.9 ± 0.3, 1.5 ± 0.5, 1.9 ± 0.6 and 2.2 ± 0.6 mmol/), MBG (5.9 ± 0.5, 6.7 ± 0.7, 7.7 ± 1.0 and 8.7 ± 1.5 mmol/L), HGBI [median(Q1–Q3)][0.8(0.2–1.2), 2.0(1.2–3.7), 3

  14. Beyond glucose: metabolic shifts in responses to the effects of the oral glucose tolerance test and the high-fructose diet in rats.

    PubMed

    Lin, Shuhai; Yang, Zhu; Liu, Hongde; Tang, Leihan; Cai, Zongwei

    2011-05-01

    High-fructose diet-fed rats as one of the insulin resistant models was used widely for understanding the mechanisms of type 2 diabetes mellitus. Systems-level metabolic profiling of the rat model, however, has not been deciphered clearly. To address this issue, mass spectrometry-based metabolomics was employed to unlock the metabolic snapshots of the oral glucose tolerance test (oGTT) effect in either healthy or diabetic rats, as well as to delineate the metabolic signatures in tissues of rats fed with high-fructose diet. Several differentiating metabolites were highlighted to reveal the metabolic perturbation of the oGTT effects in healthy and diabetic rats, which involved amino acid biosynthesis, polyunsaturated fatty acids, phospholipids and purine metabolism. Surprisingly, the patterns of relationships for the metabolic phenotypes by using data mining revealed that glucose ingestion might induce the healthy group to display its trajectory towards diabetic status, while only a very slight influence was observed on the high-fructose diet-fed rats 120 min after glucose ingestion. The data treatment for liver, skeletal muscle and brain tissues suggested that oxidative stress, such as lipid peroxidation and the declined antioxidant, the elevated amino acids and the perturbation of fatty acids, were caused by the high-fructose diet in liver and skeletal muscle tissues. On the other hand, the up-regulation in purine biosynthesis and the decreased concentrations for amino acids were observed in the cerebral cortex and hippocampus tissues. Collectively, the obtained results might provide a new insight not only for the impairment of glucose tolerance but also for the dietary style in rats.

  15. Improved oral bioavailability of probucol by dry media-milling.

    PubMed

    Li, Jia; Yang, Yan; Zhao, Meihui; Xu, Hui; Ma, Junyuan; Wang, Shaoning

    2017-09-01

    The polymer/probucol co-milled mixtures were prepared to improve drug dissolution rate and oral bioavailability. Probucol, a BCS II drug, was co-milled together with Copovidone (Kollidon VA64, VA64), Soluplus, or MCC using the dry media-milling process with planetary ball-milling equipment. The properties of the milled mixtures including morphology, crystal form, vitro drug dissolution and in vivo oral bioavailability in rats were evaluated. Probucol existed as an amorphous in the matrix of the co-milled mixtures containing VA64, which helped to enhance drug dissolution. The ternary mixture composed of VA64, RH40, and probucol showed increased dissolution rates in both sink and non-sink conditions. It also had a higher oral bioavailability compared to the reference formulation. Dry-media milling of binary or ternary mixtures composed of drug, polymer and surfactant possibly have wide applications to improve dissolution rate and oral bioavailability of water-insoluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Mango Supplementation Improves Blood Glucose in Obese Individuals

    PubMed Central

    Evans, Shirley F; Meister, Maureen; Mahmood, Maryam; Eldoumi, Heba; Peterson, Sandra; Perkins-Veazie, Penelope; Clarke, Stephen L; Payton, Mark; Smith, Brenda J; Lucas, Edralin A

    2014-01-01

    This pilot study examined the effects of freeze-dried mango (Mangifera indica L.) supplementation on anthropometrics, body composition, and biochemical parameters in obese individuals. Twenty obese adults (11 males and 9 females) ages 20- to 50-years old, received 10 g/day of ground freeze-dried mango pulp for 12 weeks. Anthropometrics, biochemical parameters, and body composition were assessed at baseline and final visits of the study. After 12 weeks, mango supplementation significantly reduced blood glucose in both male (−4.45 mg/dL, P = 0.018) and female (−3.56 mg/dL, P = 0.003) participants. In addition, hip circumference was reduced in male (−3.3 cm, P = 0.048) but not in female participants. However, there were no significant changes in body weight or composition in either gender. Our findings indicate that regular consumption of freeze-dried mango by obese individuals does not negatively impact body weight but provides a positive effect on fasting blood glucose. PMID:25210462

  17. Improved glucose tolerance after intensive life style intervention occurs without changes in muscle ceramide or triacylglycerol in morbidly obese subjects.

    PubMed

    Helge, J W; Stallknecht, B; Drachmann, T; Hellgren, L I; Jiménez-Jiménez, R; Andersen, J L; Richelsen, B; Bruun, J M

    2011-03-01

    This study investigated the effect of a 15-week life style intervention (hypocaloric diet and regular exercise) on glucose tolerance, skeletal muscle lipids and muscle metabolic adaptations in 14 female and 9 male morbidly obese subjects (age: 32.5±2.3 years, body mass index: 46.1±1.9 kg m(-2) ). Before and after the life style intervention, an oral glucose tolerance test was performed and a muscle biopsy was obtained in the fasted state. Maximal oxygen uptake was measured by an indirect test. After the intervention, body weight was decreased (P<0.05) by 11±1%, maximal oxygen uptake increased (P<0.05) by 18±5% and glucose tolerance increased (P<0.05) by 12±3%. Muscle glycogen was significantly increased by 47±14%, but muscle ceramide and triacylglycerol content remained completely unchanged. No sex difference was observed for any of these parameters, but during submaximal exercise a marked decrease (P<0.05) of 15±2% in respiratory exchange ratio was seen only in females indicating an enhanced fat oxidation. Despite a marked weight loss and an improved aerobic capacity muscle ceramide and triacylglycerol remained unchanged after intensive life style intervention, and muscle lipids hence do not seem to play a major role for the improved glucose tolerance in these morbidly obese subjects. Interestingly, only the females improved fat oxidation during submaximal exercise after the intervention implying the presence of a sex-dependent response to intensive life style adaptation. © 2010 The Authors. Acta Physiologica © 2010 Scandinavian Physiological Society.

  18. Physicians’ knowledge of and adherence to improving oral health

    PubMed Central

    2012-01-01

    Background Integration of oral health promotion into general health care has been highly recommended by the World Health Organization. Primary-care physicians can as part of their general health care promote and contribute to improved oral health care. Our aim was to investigate primary-care physicians’ knowledge of oral health, their attitudes toward delivering oral health care (OHC), and their willingness to obtain more education in this field. Methods We conducted a cross-sectional survey of all primary-care physicians working in the public health centers of Tehran city. An anonymous self-administered questionnaire queried their knowledge in pediatric- and general medicine-related areas of dentistry, providing knowledge scores to be calculated for three domains. The physicians’ attitudes toward OHC and willingness to pursue continuous education underwent evaluation with statements utilizing a 5-point Likert scale. Totally, 220 physicians took part in the survey (response rate: 92%). Chi-square test, linear and logistic regression, and t-test served for statistical analyses. Results The physicians’ knowledge score was significantly lower in the pediatric domain than in the dental and medical domains (p < 0.001). The number of physicians answering correctly to the pediatric questions was less than 40%. Almost all physicians (95%) reported it necessary for a physician to know about OHC and admitted (78%) that physicians’ general knowledge in this field is inadequate. Further, 77% of the physicians expressed a will to implement preventive oral health activities in their practice, and almost two-thirds (62%) of them showed a willingness to pursue further education about OHC. Those with higher knowledge scores had a greater willingness to deliver oral health care to their patients. Conclusions Physicians’ lack of knowledge of OHC and their generally positive attitudes toward it revealed a great need for planning of a continuous medical education program in

  19. Role of glucose transporters in the intestinal absorption of gastrodin, a highly water-soluble drug with good oral bioavailability.

    PubMed

    Cai, Zheng; Huang, Juan; Luo, Hui; Lei, Xiaolu; Yang, Zhaoxiang; Mai, Yang; Liu, Zhongqiu

    2013-07-01

    Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (Tmax) was prolonged from 28 to 72 min when orally co-administered with four times higher dose of glucose. However, the Tmax of gastrodin in diabetic rats was significantly lowered to 20 min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin.

  20. Short-Term Regulation of Lipocalin-2 but not RBP-4 During Oral Lipid Tolerance Test and Oral Glucose Tolerance Test.

    PubMed

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2016-02-01

    The postprandial regulation of lipocalin-2 and retinol binding protein-4 (RBP-4) by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of lipocalin-2 and RBP-4 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn after 0, 2, 4, and 6 h in OLTT and after 0, 1, and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of lipocalin-2 and RBP-4 were measured by enzyme-linked immunosorbent assay (ELISA). Whereas RBP-4 levels remained unchanged during OGTT, lipocalin-2 concentrations significantly decreased during OGTT. During OLTT, RBP-4 levels were not influenced, whereas lipocalin-2 levels decreased significantly and stepwise. Fasting concentrations of RBP-4 were negatively correlated with BMI and waist-hip ratio, whereas lipocalin-2 levels were positively associated with BMI and waist-hip ratio. Female users of hormonal contraception had higher RBP-4 levels than females not on contraceptives. There is no significant short-term regulation of RBP-4 by orally ingested lipids or carbohydrates. Lipocalin-2 is downregulated after lipid and carbohydrate ingestion and this kind of regulation was not predicted by age, sex, triglycerides, glucose, or insulin levels.

  1. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. Oral Iloprost Improves Endobronchial Dysplasia in Former Smokers

    PubMed Central

    Keith, Robert L.; Blatchford, Patrick J.; Kittelson, John; Minna, John D.; Kelly, Karen; Massion, Pierre P.; Franklin, Wilbur A.; Mao, Jenny; Wilson, David O.; Merrick, Daniel T.; Hirsch, Fred R.; Kennedy, Timothy C.; Bunn, Paul A.; Geraci, Mark W.; Miller, York E.

    2011-01-01

    There are no established chemopreventive agents for lung cancer, the leading cause of cancer death in the United States. Prostacyclin levels are low in lung cancer and supplementation prevents lung cancer in preclinical models. We carried out a multicenter double-blind, randomized, phase II placebo-controlled trial of oral iloprost in current or former smokers with sputum cytologic atypia or endobronchial dysplasia. Bronchoscopy was performed at study entry and after completion of six months of therapy. Within each subject, the results were calculated by using the average score of all biopsies (Avg), the worst biopsy score (Max), and the dysplasia index (DI). Change in Avg was the primary end point, evaluated in all subjects, as well as in current and former smokers. The accrual goal of 152 subjects was reached and 125 completed both bronchoscopies (60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age, tobacco exposure, and baseline histology. Baseline histology was significantly worse for current smokers (Avg 3.0) than former smokers (Avg 2.1). When compared with placebo, former smokers receiving oral iloprost exhibited a significantly greater improvement in Avg (0.41 units better, P = 0.010), in Max (1.10 units better, P = 0.002), and in DI (12.45%, P = 0.006). No histologic improvement occurred in current smokers. Oral iloprost significantly improves endobronchial histology in former smokers and deserves further study to determine if it can prevent the development of lung cancer. PMID:21636546

  3. Improving oral absorption of Salmon calcitonin by trimyristin lipid nanoparticles.

    PubMed

    Martins, S; Silva, A C; Ferreira, D C; Souto, E B

    2009-02-01

    Solid lipid nanoparticles (SLN) composed of trimyristin (solid lipid) and poloxamer 407 (surfactant) were prepared by a w/o/w emulsion technique for the incorporation of Salmon calcitonin, and further explored as protein carriers for oral delivery. Trimyristin SLN showed a mean size diameter of 200 nm with an association efficiency for calcitonin of approx. 86%. The morphology of SLN was investigated by cryo-SEM and by AFM, revealing spheroid shape SLN with a smooth surface. The in vitro release of calcitonin occurred for a period of 8 h, under both gastric and intestinal simulated pH conditions, predicting suitable properties for oral administration. The pharmacological activity of the protein was evaluated following oral dosage of calcitonin-loaded SLN in rats. SLN lowered the basal blood calcium levels by up to 20% with 500 IU/kg dose sustaining hypocalcaemia over 8 h. The results indicate that incorporation of Salmon calcitonin into trimyristin SLN is a key factor for the improvement of the efficiency of such carriers for oral delivery of proteins.

  4. Challenges of improving oral health for adults in care homes.

    PubMed

    Elliot, Victoria

    2017-08-31

    In 2016 the National Institute for Health and Care Excellence (NICE) published a guideline on oral health for adults in care homes in England. The author was a co-opted member of the NICE oral health for adults in care homes public health advisory committee. This article reviews the NICE guideline as it applies to care homes, and relates it to the results of a survey of oral care practice undertaken in a large care home organisation and the available research literature from the past 20 years. The literature and survey results suggest that, if translated into practice, the NICE guideline could do much to improve oral health for adults in care homes. The survey highlighted that 85% of residents required support from carers to undertake mouth care. It also found that care homes experienced significant difficulties in accessing dental services for residents. The author concludes that providers need to equip staff with the necessary knowledge and skills to undertake mouth care and to give this area of personal care greater priority. Finally, the author suggests that the Care Quality Commission could ensure that the NICE guideline is translated into practice in care homes.

  5. The Clamp-Like Index: a novel and highly sensitive insulin sensitivity index to calculate hyperinsulinemic clamp glucose infusion rates from oral glucose tolerance tests in nondiabetic subjects.

    PubMed

    Anderwald, Christian; Anderwald-Stadler, Marietta; Promintzer, Miriam; Prager, Gerhard; Mandl, Martina; Nowotny, Peter; Bischof, Martin G; Wolzt, Michael; Ludvik, Bernhard; Kästenbauer, Thomas; Pacini, Giovanni; Luger, Anton; Krebs, Michael

    2007-09-01

    Insulin resistance, the underlying pathophysiological mechanism of the metabolic syndrome, can not only predict type 2 diabetes development but also cardiovascular disease. Thus, precise insulin resistance measurement in individuals at risk for metabolic diseases would support clinical risk stratification. However, the gold standard for measuring insulin resistance, the hyperinsulinemic clamp test, is too labor intensive to be performed in large clinical studies/settings. Using plasma glucose and C-peptide concentrations from oral glucose tolerance tests (OGTTs), we developed the novel "clamp-like index" (CLIX) for insulin sensitivity calculation and compared CLIX to clamp glucose infusion rates (GIR) (100-120 min). We evaluated CLIX in 89 nondiabetic subjects (58 female and 31 male, aged 45 +/- 1 years, BMI 27.5 +/- 0.8 kg/m(2)) who underwent frequently sampled 3-h 75-g OGTTs and 2-h hyperinsulinemic-isoglycemic clamp (40 mU/min per m(2)) tests. CLIX, calculated as serum creatinine (x0.85 if male)/(mean AUC(glucose) x mean AUC(C-peptide)) x 6,600, was highly correlated (r = 0.670, P < 10(-12)) with and comparable to clamp GIRs(100-120 min). In subgroup analyses, GIRs(100-120 min) were lower (P < 0.005) in type 2 diabetic offspring (6.2 +/- 0.7 mg x min(-1) x kg(-1)) than in sex-, age-, and BMI-matched subjects without a family history of type 2 diabetes (8.6 +/- 0.5 mg x min(-1) x kg(-1)), which was also reflected by CLIX (insulin-resistant offspring 6.4 +/- 0.6 vs. those without a family history of type 2 diabetes 9.0 +/- 0.5; P < 0.002). When compared with normal-weight subjects (GIR 8.8 +/- 0.4 mg x min(-1) x kg(-1); CLIX 9.0 +/- 0.5), both GIRs(100-120 min) and CLIX of obese (5.2 +/- 0.9 mg x min (-1) x kg(-1); 5.7 +/- 0.9) and morbidly obese (2.4 +/- 0.4 mg x min (-1) x kg(-1); 3.3 +/- 0.5) humans were lower (each P < 0.02). CLIX, a novel index obtained from plasma OGTT glucose and C-peptide levels and serum creatinine, without inclusion of anthropometrical

  6. Sulforaphane improves disrupted ER-mitochondria interactions and suppresses exaggerated hepatic glucose production.

    PubMed

    Tubbs, Emily; Axelsson, Annika S; Vial, Guillaume; Wollheim, Claes B; Rieusset, Jennifer; Rosengren, Anders H

    2017-09-18

    Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs. We used proximity ligation assays, analysis of ER stress markers and glucose production assays in hepatoma cell lines, primary mouse hepatocytes and diabetic animal models. SFN counteracted the increase of glucose production in palmitate-treated mouse hepatocytes. SFN also counteracted palmitate-induced MAM disruptions. Moreover, SFN decreased the ER stress markers CHOP and Grp78. In ob/ob mice, SFN improved glucose tolerance and reduced exaggerated glucose production. In livers of these mice, SFN increased MAM protein content, restored impaired VDAC1-IP3R1 interactions and reduced ER stress markers. In mice on HFHSD, SFN improved glucose tolerance, MAM protein content and ER-mitochondria interactions to a similar extent to that of metformin. The present findings show that MAMs are severely reduced in animal models of glucose intolerance, which reinforces the role of MAMs as a hub for insulin signaling in the liver. We also show that SFN restores MAMs and improves glucose tolerance by a similar magnitude to that of metformin. These data highlight SFN as a new potential anti-diabetic compound. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat.

    PubMed

    Bernard, Jeffrey R; Liao, Yi-Hung; Ding, Zhenping; Hara, Daisuke; Kleinert, Maximilian; Nelson, Jeffrey L; Ivy, John L

    2013-07-01

    The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.

  8. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

    PubMed

    Xia, Xuan; Yan, Jinhua; Shen, Yunfeng; Tang, Kuanxiao; Yin, Jun; Zhang, Yanhua; Yang, Dongjie; Liang, Hua; Ye, Jianping; Weng, Jianping

    2011-02-03

    Berberine (BBR) is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French). It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS) was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP) level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

  9. A Novel Role for Subcutaneous Adipose Tissue in Exercise-Induced Improvements in Glucose Homeostasis

    PubMed Central

    Stanford, Kristin I.; Middelbeek, Roeland J.W.; Townsend, Kristy L.; Lee, Min-Young; Takahashi, Hirokazu; So, Kawai; Hitchcox, Kristen M.; Markan, Kathleen R.; Hellbach, Katharina; Hirshman, Michael F.; Tseng, Yu-Hua

    2015-01-01

    Exercise training improves whole-body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues, including adipose tissue. To determine whether exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from exercise-trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, 9 days post-transplantation, mice receiving scWAT from exercise-trained mice had improved glucose tolerance and enhanced insulin sensitivity compared with mice transplanted with scWAT from sedentary or sham-treated mice. Mice transplanted with scWAT from exercise-trained mice had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat–fed recipient mice were transplanted with scWAT from exercise-trained mice. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT, including the increased expression of ∼1,550 genes involved in numerous cellular functions including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis. PMID:25605808

  10. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

    PubMed

    Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

    2014-12-02

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

  11. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly

    PubMed Central

    Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

    2014-01-01

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60–85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [18F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults. PMID:25463973

  12. Physicochemical characteristics of polysaccharide conjugates prepared from fresh tea leaves and their improving impaired glucose tolerance.

    PubMed

    Chen, Xiaoqiang; Fang, Yapeng; Nishinari, Katsuyoshi; We, Heng; Sun, Chaochao; Li, Jianrong; Jiang, Yongwen

    2014-11-04

    Hot-water extracts were prepared from fresh tea leaves and fractionated by DEAE-cellulose DE-52 column chromatography to yield one unexplored polysaccharide-conjugate fraction TPC-L (tea polysaccharide conjugates). Chemical components, molecular weight and its distribution, water vapor sorption properties, zeta potentials and optical characteristics of TPC-L were investigated. As compared with injured cell group, the two dosages of TPC-L (150 and 300 μg/mL) were discovered to possess remarkably protective effect on human umbilical vein endothelial cells against impairments induced by high glucose in a dose-dependent manner (p < 0.05, p < 0.001, respectively). Compared with group NC (normal control), the ingestion of 40 mg/kg of TPC-L could significantly reduce blood glucose levels of normal mice ingesting starch, and significant difference of AUC (area under the curve of blood glucose) and ΔAUC (p < 0.05, p < 0.01) at the postprandial time point of 0.5 and 1.0 h were observed. The three dosages of TPC-L (10, 40 and 160 mg/kg) did not significantly lower postprandial blood glucose levels of normal mice ingesting glucose. TPC-L could improve starch tolerance to prevent impaired glucose tolerance (IGT) from developing into diabetes as well as protective effects on HUVE cells against impairments induced by high glucose It was suggested that TPC-L improved IGT through its capability of inhibition on digestive enzymes.

  13. Intake of St John's wort improves the glucose tolerance in healthy subjects who ingest metformin compared with metformin alone.

    PubMed

    Stage, Tore Bjerregaard; Pedersen, Rasmus Steen; Damkier, Per; Christensen, Mette Marie Hougaard; Feddersen, Søren; Larsen, John Teilmann; Højlund, Kurt; Brøsen, Kim

    2015-02-01

    Our objective was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St John's wort and the antidiabetic drug metformin. We performed an open cross-over study in 20 healthy male subjects, who received 1 g of metformin twice daily for 1 week with and without 21 days of preceding and concomitant treatment with St John's wort. The pharmacokinetics of metformin was determined, and a 2 h oral glucose tolerance test was performed. St John's wort decreased the renal clearance of metformin but did not affect any other metformin pharmacokinetic parameter. The addition of St John's wort decreased the area under the glucose concentration-time curve [702 (95% confidence interval, 643-761) vs. 629 min*mmol/L (95% confidence interval, 568-690), P = 0.003], and this effect was caused by a statistically significant increase in the acute insulin response. St John's wort improves glucose tolerance by enhancing insulin secretion independently of insulin sensitivity in healthy male subjects taking metformin. © 2014 The British Pharmacological Society.

  14. Improved glucose tolerance after effective lipid-lowering therapy with bezafibrate in a patient with lipoatrophic diabetes mellitus: a putative role for Randle's cycle in its pathogenesis?

    PubMed

    Panz, V R; Wing, J R; Raal, F J; Kedda, M A; Joffe, B I

    1997-03-01

    This report describes a patient with lipoatrophic diabetes mellitus (LDM), which is a rare clinical syndrome characterized by lipoatrophy and severe insulin resistance. Although a genetic abnormality is suspected in the development of LDM, no functional mutations in key domains of the insulin receptor gene were detected. Therapy was directed primarily at decreasing the availability of non-esterified fatty acids (NEFA), and thereby improving glucose tolerance (Randle's cycle), by the administration of a lipid-lowering drug, bezafibrate. Serial changes in fasting levels of the hormones of glucose homeostasis and lipids were measured, as well as glucose and insulin responses to a 75-g oral glucose challenge at onset and following 3 and 6 months of fibrate therapy. Progressive reductions in the patient's levels of triglycerides and NEFA were paralleled by an improvement in beta-cell function, a decrease in insulin resistance, and the attainment of normal glucose homeostasis. We conclude that the pathogenesis of LDM may be related primarily to abnormal regulation of lipid, rather than glucose, metabolism.

  15. Improving oral health among schoolchildren - which approach is best?

    PubMed

    Davies, G; Bridgman, C

    2011-01-22

    This opinion piece considers the focus of the coalition government on improving the dental health of schoolchildren. It shows how oral health improvement teams have moved on from approaches which involve the education of children alone. More modern interventions are selected from a palette of evidence-informed options to suit the needs of the local population. Such options should ensure a multilevel approach. A plea is made for any new guidance to be informed by dental public health specialists who have practical experience to ensure that outdated methods are not re-introduced.

  16. Oral glucose before venepuncture relieves neonates of pain, but stress is still evidenced by increase in oxygen consumption, energy expenditure, and heart rate.

    PubMed

    Bauer, Karl; Ketteler, Jörg; Hellwig, Magdalena; Laurenz, Maren; Versmold, Hans

    2004-04-01

    Oral glucose was recommended as pain therapy during venepuncture in neonates. It is unclear whether this intervention reduces excess oxygen consumption (o(2)), energy loss, or cardiovascular destabilization associated with venepuncture, and whether <2 mL glucose solution is effective. We tested the hypothesis that oral glucose solution attenuates the increases in neonatal oxygen consumption, energy expenditure (EE), and heart rate associated with venepuncture for two different volumes of glucose solution (2 and 0.4 mL). In this prospective, randomized, controlled, double-blind trial, 58 neonates (gestational age, 31-42 wk; postnatal age, 1-7 d) were randomized to 2 mL glucose 30%, 0.4 mL glucose 30%, or 2 mL water by mouth before venepuncture. The videotaped behavioral pain reactions were scored with the Premature Infant Pain Profile. Cry duration, o(2), EE (indirect calorimetry), and heart rate were measured. The 2 mL glucose solution reduced pain score and crying after venepuncture compared with controls [median pain score, 5.5 (interquartile range, 4-9) versus 11 (7-12), p = 0.01; median duration of first cry, 0 s (0-43 s) versus 13 s (2-47 s), p < 0.05, respectively]. The 0.4 mL glucose solution had no effect. The 2 mL glucose solution did not attenuate the o(2) increase during venepuncture (1.5 +/- 0.2 mL/kg min (water) versus 1.7 +/- 0.5 (0.4 mL glucose) versus 1.1 +/- 0.2 (2 mL glucose) (mean +/- SEM) nor EE nor heart rate. We conclude that oral administration of 2 mL glucose 30% before venepuncture reduced pain expression and crying, but did not prevent the rise in o(2), EE, or heart rate. Alternative therapies against the stress of nonpainful handling during venepuncture should be explored.

  17. Comparison of A1C to Oral Glucose Tolerance Test for the Diagnosis of Prediabetes in Overweight and Obese Youth.

    PubMed

    Khokhar, Aditi; Naraparaju, Gayathri; Friedman, Miriam; Perez-Colon, Sheila; Umpaichitra, Vatcharapan; Chin, Vivian L

    2017-07-01

    IN BRIEF This study reports performance of A1C against the oral glucose tolerance test (OGTT) in predicting prediabetes among overweight and obese African-American and Caribbean children. A retrospective chart review was completed for 230 children. Receiver operating characteristic curves were generated to find the predictive performances of different tests against the OGTT. A1C alone is a poor discriminator of prediabetes in our study population, with low sensitivity (70%) and specificity (48.8%). BMI z score, A1C, and homeostatic model assessment of insulin resistance are significant predictors of prediabetes and, when taken together, provide better discrimination for prediabetes.

  18. VB12-coated Gel-Core-SLN containing insulin: Another way to improve oral absorption.

    PubMed

    He, Haibing; Wang, Puxiu; Cai, Cuifang; Yang, Rui; Tang, Xing

    2015-09-30

    To improve the oral absorption of insulin, a novel carrier of Vitamin B12 (VB12) gel core solid lipid nanopaticles (Gel-Core-SLN, GCSLN) was designed with a gel core, lipid matrix and VB12-coated surface. VB12-stearate was synthesized and characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). Sol-gel conversion following ultrasonic heating and double emulsion technology were combined to implant the insulin-containing gel into solid lipid nanoparticles (SLN). The influence of the mode of administration, food, the amount of VB12-stearate and the particle size on the oral absorption of insulin incorporated in the VB12-GCSLN was investigated. The determined partition coefficient (LogP) of VB12-stearate in a dichloromethane (DCM)-water system was 3.4. This new structure of VB12-GCSLN had higher insulin encapsulation efficiency (EE) of 55.9%, a lower burst release of less than 10% in the first 2h. In vivo studies demonstrated that stronger absorption of insulin with a relative pharmacological availability (PA) of 9.31% compared with the normal insulin-loaded SLN and GCSLN and fairly stable blood glucose levels up to 12h were maintained without any sharp fluctuations. This study suggests that VB12-GCSLN containing insulin appears to be a promising nano carrier for oral delivery of biomacromolecules with relatively high pharmacological availability. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity

    PubMed Central

    Prawitt, Janne; Abdelkarim, Mouaadh; Stroeve, Johanna H.M.; Popescu, Iuliana; Duez, Helene; Velagapudi, Vidya R.; Dumont, Julie; Bouchaert, Emmanuel; van Dijk, Theo H.; Lucas, Anthony; Dorchies, Emilie; Daoudi, Mehdi; Lestavel, Sophie; Gonzalez, Frank J.; Oresic, Matej; Cariou, Bertrand; Kuipers, Folkert; Caron, Sandrine; Staels, Bart

    2011-01-01

    OBJECTIVE Bile acids (BA) participate in the maintenance of metabolic homeostasis acting through different signaling pathways. The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity. However, the role of FXR in obesity and associated complications, such as dyslipidemia and insulin resistance, has not been directly assessed. RESEARCH DESIGN AND METHODS Here, we evaluate the consequences of FXR deficiency on body weight development, lipid metabolism, and insulin resistance in murine models of genetic and diet-induced obesity. RESULTS FXR deficiency attenuated body weight gain and reduced adipose tissue mass in both models. Surprisingly, glucose homeostasis improved as a result of an enhanced glucose clearance and adipose tissue insulin sensitivity. In contrast, hepatic insulin sensitivity did not change, and liver steatosis aggravated as a result of the repression of β-oxidation genes. In agreement, liver-specific FXR deficiency did not protect from diet-induced obesity and insulin resistance, indicating a role for nonhepatic FXR in the control of glucose homeostasis in obesity. Decreasing elevated plasma BA concentrations in obese FXR-deficient mice by administration of the BA sequestrant colesevelam improved glucose homeostasis in a FXR-dependent manner, indicating that the observed improvements by FXR deficiency are not a result of indirect effects of altered BA metabolism. CONCLUSIONS Overall, FXR deficiency in obesity beneficially affects body weight development and glucose homeostasis. PMID:21593203

  20. Relationships of the early insulin secretory response and oral disposition index with gastric emptying in subjects with normal glucose tolerance.

    PubMed

    Marathe, Chinmay S; Rayner, Christopher K; Lange, Kylie; Bound, Michelle; Wishart, Judith; Jones, Karen L; Kahn, Steven E; Horowitz, Michael

    2017-02-01

    The oral disposition index, the product of the early insulin secretory response during an oral glucose tolerance test and insulin sensitivity, is used widely for both the prediction of, and evaluation of the response to interventions, in type 2 diabetes. Gastric emptying, which determines small intestinal exposure of nutrients, modulates postprandial glycemia. The aim of this study was to determine whether the insulin secretory response and the disposition index (DI) related to gastric emptying in subjects with normal glucose tolerance. Thirty-nine subjects consumed a 350 mL drink containing 75 g glucose labeled with (99m)Tc-sulfur colloid. Gastric emptying (by scintigraphy), blood glucose (G) and plasma insulin (I) were measured between t = 0-120 min. The rate of gastric emptying was derived from the time taken for 50% emptying (T50) and expressed as kcal/min. The early insulin secretory response was estimated by the ratio of the change in insulin (∆I0-30) to that of glucose at 30 min (∆G0-30) represented as ∆I0-30/∆G0-30 Insulin sensitivity was estimated as 1/fasting insulin and the DI was then calculated as ∆I0-30/∆G0-30 × 1/fasting insulin. There was a direct relationship between ∆G0-30 and gastric emptying (r = 0.47, P = 0.003). While there was no association of either ∆I0-30 (r = -0.16, P = 0.34) or fasting insulin (r = 0.21, P = 0.20), there were inverse relationships between the early insulin secretory response (r = -0.45, P = 0.004) and the DI (r = -0.33, P = 0.041), with gastric emptying. We conclude that gastric emptying is associated with both insulin secretion and the disposition index in subjects with normal glucose tolerance, such that when gastric emptying is relatively more rapid, both the early insulin secretory response and the disposition index are less. These findings should be interpreted as "hypothesis generating" and provide the rationale for longitudinal studies to examine the impact of baseline

  1. Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

    PubMed Central

    Li, Haiying; Pan, Tingting; Cui, Ying; Li, Xiaxia; Gao, Jiefang; Yang, Wenzhi; Shen, Shigang

    2016-01-01

    The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM. PMID:27540291

  2. Oral magnesium supplementation improves vascular function in elderly diabetic patients.

    PubMed

    Barbagallo, Mario; Dominguez, Ligia J; Galioto, Antonio; Pineo, Antonella; Belvedere, Mario

    2010-09-01

    Magnesium (Mg) ions directly influence vascular tone and responsiveness and are cofactors for acetylcholine-induced endothelium-dependent relaxation. Alterations in extracellular Mg are able to modify the formation and release of nitric oxide (NO), altering arterial smooth muscle tone. Previous in vivo studies in humans have shown that parenteral or oral Mg supplementation increase endothelial-dependent vasodilation. The aim of the present study was to evaluate the effects of Mg oral supplementation on endothelial function in elderly diabetic and hypertensive subjects. Sixty elderly (≥ 65 years) diabetic patients were recruited (mean age: 71.1 ± 6.1 years; M/F: 35/25). Endothelial function, evaluated by non-invasive flow-mediated dilatation of the brachial artery, as well as anthropometric and laboratory data, including ionized Mg (Mg-ion), were measured in all patients before and after one-month. Thirty patients underwent oral Mg supplementation with 4.5 g/day of Mg pidolate (368 mg/day of Mg ion), while the rest were used as a control group. The usual management of diabetes and hypertension was not changed during the month of study participation for all the patients. In the group of patients that underwent Mg supplementation, Mg-ion concentration significantly increased from 0.42 ± 0.05 mmol/L to 0.49 ± 0.06 mmol/L; p < 0.05. Mg intervention resulted in a significant improvement of the post-ischemic endothelial-dependent flow-mediated dilation (from 3.3 ± 3.6% to 8.4 ± 3.9%; p < 0.05). No significant differences were found, either in ion-Mg or endothelial function, in the control group. In conclusion, the present study suggests that oral Mg improves endothelial function in diabetic elderly subjects.

  3. Sensor Monitoring of Physical Activity to Improve Glucose Management in Diabetic Patients: A Review

    PubMed Central

    Ding, Sandrine; Schumacher, Michael

    2016-01-01

    Diabetic individuals need to tightly control their blood glucose concentration. Several methods have been developed for this purpose, such as the finger-prick or continuous glucose monitoring systems (CGMs). However, these methods present the disadvantage of being invasive. Moreover, CGMs have limited accuracy, notably to detect hypoglycemia. It is also known that physical exercise, and even daily activity, disrupt glucose dynamics and can generate problems with blood glucose regulation during and after exercise. In order to deal with these challenges, devices for monitoring patients’ physical activity are currently under development. This review focuses on non-invasive sensors using physiological parameters related to physical exercise that were used to improve glucose monitoring in type 1 diabetes (T1DM) patients. These devices are promising for diabetes management. Indeed they permit to estimate glucose concentration either based solely on physical activity parameters or in conjunction with CGM or non-invasive CGM (NI-CGM) systems. In these last cases, the vital signals are used to modulate glucose estimations provided by the CGM and NI-CGM devices. Finally, this review indicates possible limitations of these new biosensors and outlines directions for future technologic developments. PMID:27120602

  4. Neural network incorporating meal information improves accuracy of short-time prediction of glucose concentration.

    PubMed

    Zecchin, Chiara; Facchinetti, Andrea; Sparacino, Giovanni; De Nicolao, Giuseppe; Cobelli, Claudio

    2012-06-01

    Diabetes mellitus is one of the most common chronic diseases, and a clinically important task in its management is the prevention of hypo/hyperglycemic events. This can be achieved by exploiting continuous glucose monitoring (CGM) devices and suitable short-term prediction algorithms able to infer future glycemia in real time. In the literature, several methods for short-time glucose prediction have been proposed, most of which do not exploit information on meals, and use past CGM readings only. In this paper, we propose an algorithm for short-time glucose prediction using past CGM sensor readings and information on carbohydrate intake. The predictor combines a neural network (NN) model and a first-order polynomial extrapolation algorithm, used in parallel to describe, respectively, the nonlinear and the linear components of glucose dynamics. Information on the glucose rate of appearance after a meal is described by a previously published physiological model. The method is assessed on 20 simulated datasets and on 9 real Abbott FreeStyle Navigator datasets, and its performance is successfully compared with that of a recently proposed NN glucose predictor. Results suggest that exploiting meal information improves the accuracy of short-time glucose prediction.

  5. Gestational Diabetes Mellitus (GDM): Relationship Between Higher Cutoff Values for 100 g Oral Glucose Tolerance Test (OGTT) and Insulin Requirement During Pregnancy.

    PubMed

    Ares, Jessica; Martín-Nieto, Alicia; Díaz-Naya, Lucía; Tartón, Teresa; Menéndez-Prada, Teresa; Ragnarsson, Cecilia S; Delgado-Álvarez, Elías; Menéndez-Torre, Edelmiro

    2017-07-01

    Objectives To study if there is any relationship about higher cutoff values for 100 g oral glucose tolerance test and the need for insulin in women diagnosed with gestational diabetes. Materials and Methods This is a retrospective population-based study of 201 women diagnosed with Gestational Diabetes Mellitus (GDM) between January 2012 and June 2014 in the area of Oviedo, Asturias, Spain. According to diagnostic criteria recommended by GEDE, NDDG, gestational diabetes is diagnosed if two or more plasma glucose levels meet or exceed the following threshold: fasting glucose of 105 mg/dl, 1-h 190 mg/dl, 2-h 165 mg/dl, or 3-h 145 mg/dl. We aim to know if there is any relationship between higher cutoffs and insulin requirement. Results 36 out of 201 patients (17.91%) needed insulin to achieve the targets of blood glucose control. There were no differences in mean maternal age and birthweights. Fasting blood glucose levels were significantly higher in women with further need for insulin than those who only needed diet and exercise (p < 0.001). Also, blood glucose levels 2 h after the oral glucose intake were statistically different between the two groups (p 0.032). AUC for fasting glucose value was the highest according to ROC curve. Conclusions Fasting cutoff vales for 100 g oral glucose tolerance test are consistently higher in women diagnosed with Gestational Diabetes that further needed insulin to achieve adequate blood glucose control. The positive predictive value of fasting glucose value 105 mg/dl on OGTT was 81.1%, whereas for the cut-off 95 mg/dl it was 54.0%.

  6. Germinated Pigmented Rice (Oryza Sativa L. cv. Superhongmi) Improves Glucose and Bone Metabolisms in Ovariectomized Rats

    PubMed Central

    Chung, Soo Im; Ryu, Su Noh; Kang, Mi Young

    2016-01-01

    The effect of germinated Superhongmi, a reddish brown pigmented rice cultivar, on the glucose profile and bone turnover in the postmenopausal-like model of ovariectomized rats was determined. The ovariectomized Sprague-Dawley rats were randomly divided into three dietary groups (n = 10): normal control diet (NC) and normal diet supplemented with non-germinated Superhongmi (SH) or germinated Superhongmi (GSH) rice powder. After eight weeks, the SH and GSH groups showed significantly lower body weight, glucose and insulin concentrations, levels of bone resorption markers and higher glycogen and 17-β-estradiol contents than the NC group. The glucose metabolism improved through modulation of adipokine production and glucose-regulating enzyme activities. The GSH rats exhibited a greater hypoglycemic effect and lower bone resorption than SH rats. These results demonstrate that germinated Superhongmi rice may potentially be useful in the prevention and management of postmenopausal hyperglycemia and bone turnover imbalance. PMID:27775654

  7. Acute rapamycin treatment improved glucose tolerance through inhibition of hepatic gluconeogenesis in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Terrier, Frédéric; Seiliez, Iban; Skiba-Cassy, Sandrine

    2014-11-15

    Our aim was to investigate the potential role of TOR (target of rapamycin) signaling pathway in the regulation of hepatic glucose metabolism in rainbow trout. Fasted fish were first treated with a single intraperitoneal injection of rapamycin or vehicle and then submitted to a second intraperitoneal administration of glucose 4 h later. Our results revealed that intraperitoneal administration of glucose induced hyperglycemia for both vehicle and rapamycin treatments, which peaked at 2 h. Plasma glucose level in vehicle-treated fish was significantly higher than in rapamycin-treated fish at 8 and 17 h, whereas it remained at the basal level in rapamycin-treated fish. Glucose administration significantly enhanced the phosphorylation of Akt and ribosomal protein S6 kinase (S6K1) in vehicle-treated fish, while rapamycin completely abolished the activation of S6K1 in rapamycin-treated fish, without inhibiting the phosphorylation of Akt on Thr-308 or Ser-473. Despite the lack of significant variation in phosphoenolpyruvate carboxykinase mRNA abundance, mRNA abundance for glucokinase (GK), glucose 6-phosphatase (G6Pase) I and II, and fructose 1,6-bisphosphatase (FBPase) was reduced by rapamycin 17 h after glucose administration. The inhibition effect of rapamycin on GK and FBPase was further substantiated at the activity level. The suppression of GK gene expression and activity by rapamycin provided the first in vivo evidence in fish that glucose regulates hepatic GK gene expression and activity through a TORC1-dependent manner. Unlike in mammals, we observed that acute rapamycin treatment improved glucose tolerance through the inhibition of hepatic gluconeogenesis in rainbow trout. Copyright © 2014 the American Physiological Society.

  8. Optimized zein nanospheres for improved oral bioavailability of atorvastatin

    PubMed Central

    Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama AA

    2015-01-01

    Background This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug. Methods Twelve experimental runs of atorvastatin–zein nanosphere formula were formulated by a liquid–liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X1), pH (X2), and stirring time (X3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y1), zeta potential (Y2), drug loading efficiency (Y3), drug encapsulation efficiency (Y4), and yield (Y5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin–zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet. Results The optimized atorvastatin–zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin–zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet. Conclusion The atorvastatin–zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability. PMID:26150716

  9. Rare sugar D-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

    PubMed

    Hossain, Mohammad A; Kitagaki, Shigeru; Nakano, Daisuke; Nishiyama, Akira; Funamoto, Yasunobu; Matsunaga, Toru; Tsukamoto, Ikuko; Yamaguchi, Fuminori; Kamitori, Kazuyo; Dong, Youyi; Hirata, Yuko; Murao, Koji; Toyoda, Yukiyasu; Tokuda, Masaaki

    2011-02-04

    A rare sugar, D-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of D-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% D-psicose or 5% D-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, D-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that D-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed D-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. D-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that D-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.

  10. Immunoneutralization of endogenous glucagon reduces hepatic glucose output and improves long-term glycemic control in diabetic ob/ob mice.

    PubMed

    Sørensen, Heidi; Brand, Christian L; Neschen, Susanne; Holst, Jens Juul; Fosgerau, Keld; Nishimura, Erica; Shulman, Gerald I

    2006-10-01

    In type 2 diabetes, glucagon levels are elevated in relation to the prevailing insulin and glucose levels. The relative hyperglucagonemia is linked to increased hepatic glucose output (HGO) and hyperglycemia. Antagonizing the effects of glucagon is therefore considered an attractive target for treatment of type 2 diabetes. In the current study, effects of eliminating glucagon signaling with a glucagon monoclonal antibody (mAb) were investigated in the diabetic ob/ob mouse. Acute effects of inhibiting glucagon action were studied by an oral glucose tolerance test (OGTT) and by measurement of HGO. In addition, the effects of subchronic (5 and 14 days) glucagon mAb treatment on plasma glucose, insulin, triglycerides, and HbA1c (A1C) levels were investigated. Glucagon mAb treatment reduced the area under the curve for glucose after an OGTT, reduced HGO, and increased the rate of hepatic glycogen synthesis. Glucagon mAb treatment for 5 days lowered plasma glucose and triglyceride levels, whereas 14 days of glucagon mAb treatment reduced A1C. In conclusion, acute and subchronic neutralization of endogenous glucagon improves glycemic control, thus supporting the contention that glucagon antagonism may represent a beneficial treatment of diabetes.

  11. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus.

    PubMed Central

    Cohen, N; Halberstam, M; Shlimovich, P; Chang, C J; Shamoon, H; Rossetti, L

    1995-01-01

    We examined the in vivo metabolic effects of vanadyl sulfate (VS) in non-insulin-dependent diabetes mellitus (NIDDM). Six NIDDM subjects treated with diet and/or sulfonylureas were examined at the end of three consecutive periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo for 2 wk. Euglycemic hyperinsulinemic (30 mU/m2.min) clamps and oral glucose tolerance tests were performed at the end of each study period. Glycemic control at baseline was poor (fasting plasma glucose 210 +/- 19 mg/dl; HbA1c 9.6 +/- 0.6%) and improved after treatment (181 +/- 14 mg/dl [P < 0.05], 8.8 +/- 0.6%, [P < 0.002]); fasting and post-glucose tolerance test plasma insulin concentrations were unchanged. After VS, the glucose infusion rate during the clamp was increased (by approximately 88%, from 1.80 to 3.38 mg/kg.min, P < 0.0001). This improvement was due to both enhanced insulin-mediated stimulation of glucose uptake (rate of glucose disposal [Rd], +0.89 mg/kg.min) and increased inhibition of HGP (-0.74 mg/kg.min) (P < 0.0001 for both). Increased insulin-stimulated glycogen synthesis (+0.74 mg/kg.min, P < 0.0003) accounted for > 80% of the increased Rd after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The Km of skeletal muscle glycogen synthase was lowered by approximately 30% after VS treatment (P < 0.05). These results indicate that 3 wk of treatment with VS improves hepatic and peripheral insulin sensitivity in insulin-resistant NIDDM humans. These effects were sustained for up to 2 wk after discontinuation of VS. Images PMID:7769096

  12. SGLT2 Deletion Improves Glucose Homeostasis and Preserves Pancreatic β-Cell Function

    PubMed Central

    Jurczak, Michael J.; Lee, Hui-Young; Birkenfeld, Andreas L.; Jornayvaz, Francois R.; Frederick, David W.; Pongratz, Rebecca L.; Zhao, Xiaoxian; Moeckel, Gilbert W.; Samuel, Varman T.; Whaley, Jean M.; Shulman, Gerald I.; Kibbey, Richard G.

    2011-01-01

    OBJECTIVE Inhibition of the Na+-glucose cotransporter type 2 (SGLT2) is currently being pursued as an insulin-independent treatment for diabetes; however, the behavioral and metabolic consequences of SGLT2 deletion are unknown. Here, we used a SGLT2 knockout mouse to investigate the effect of increased renal glucose excretion on glucose homeostasis, insulin sensitivity, and pancreatic β-cell function. RESEARCH DESIGN AND METHODS SGLT2 knockout mice were fed regular chow or a high-fat diet (HFD) for 4 weeks, or backcrossed onto the db/db background. The analysis used metabolic cages, glucose tolerance tests, euglycemic and hyperglycemic clamps, as well as isolated islet and perifusion studies. RESULTS SGLT2 deletion resulted in a threefold increase in urine output and a 500-fold increase in glucosuria, as well as compensatory increases in feeding, drinking, and activity. SGLT2 knockout mice were protected from HFD-induced hyperglycemia and glucose intolerance and had reduced plasma insulin concentrations compared with controls. On the db/db background, SGLT2 deletion prevented fasting hyperglycemia, and plasma insulin levels were also dramatically improved. Strikingly, prevention of hyperglycemia by SGLT2 knockout in db/db mice preserved pancreatic β-cell function in vivo, which was associated with a 60% increase in β-cell mass and reduced incidence of β-cell death. CONCLUSIONS Prevention of renal glucose reabsorption by SGLT2 deletion reduced HFD- and obesity-associated hyperglycemia, improved glucose intolerance, and increased glucose-stimulated insulin secretion in vivo. Taken together, these data support SGLT2 inhibition as a viable insulin-independent treatment of type 2 diabetes. PMID:21357472

  13. Investigation of the correlation between 100 gram oral glucose tolerance test results and maternal leptin levels during pregnancy

    PubMed Central

    Şengül, Özlem Baykara; Mungan, Tamer; Erdemoğlu, Evrim; İslamoğlu, Göksel; Kıyak, Nuran

    2009-01-01

    Objective To investigate the correlation between maternal leptin levels and 100 gram oral glucose test (OGTT) results as well as the correlation between leptin levels and the development of gestational diabetes mellitus (GDM) and glucose intolerance during pregnancy. Material and Method: 104 subjects with gestational weeks ranging from 24 to 32 weeks who had increased 50 gr OGTT values (>140) were included in this study. After the screening test, 100 gr OGTT was administered to the subjects. Sixty cases were selected from these subjects; twenty patients with one abnormal test result were identified as “glucose intolerant” group (Group 1), 20 patients with two abnormal test values were diagnosed with GDM (Group 2) and 20 patients with normal test results constituted the control group. The serum leptin levels of the groups were measured with enzyme linked immunosorbent assay (ELISA). Results The serum leptin level was 8.4±5.1 ng/ml for group 1, 9.1±5.3 ng/ml for group 2 and 6.3±4.6 ng/ml for the control group. Although serum leptin levels for group 1 and 2 was observed to be higher than the control group, the result was not statistically significant (p>0.05). This result did not change after adjusting for body mass index (BMI). Conclusion There is no statistically significant difference between leptin levels among three groups. PMID:24591860

  14. The effects of tonicity, glucose concentration and temperature of an oral rehydration solution on its absorption and elimination.

    PubMed

    Sosa León, L A; Davie, A J; Hodgson, D R; Rose, R J

    1995-11-01

    Effects of different tonicities, glucose concentrations and temperatures of an oral rehydration solution (ORS) on its uptake and elimination in resting horses were studied. Fluid and electrolyte deficits similar to those occurring during prolonged exercise were induced by the administration of 1 mg/kg bwt of frusemide i.m., 3 h prior to the ORS. Fluid was administered via nasogastric tube at a volume equivalent to 4% bodyweight, which approximated diuretic induced losses. The uptake of fluid was evaluated by changes in haematocrit (PCV) and plasma total protein concentration (TP). Changes in electrolyte balance were studied by measurements of plasma and urinary electrolyte concentrations while changes in bodyweight, urine volume and faecal water content were used to estimate retention of the administered fluids. Changes in acid base status were assessed from venous blood bicarbonate values. Fluid tonicity had a major effect on the uptake and elimination of the ORS. The hypertonic fluid (628 mOsm/kg bwt) was less rapidly absorbed and resulted in more rapid fluid and electrolyte excretion than the isotonic (314 mOsm/kg bwt) and hypotonic (water) fluids. The inclusion of glucose did not enhance the absorption of the ORS, although fluids containing higher concentrations of electrolytes resulted in more rapid elimination of fluid in urine. There was a direct relationship between higher concentrations of sodium in the ORS, plasma sodium values and osmolality. Fluid temperature (5, 21 and 37 degrees C) had no demonstrable effect on absorption of the ORS and elimination of fluids post administration. We concluded that while glucose concentration and fluid temperature have minimal effects on fluid absorption and elimination, fluid tonicity was a key element in the uptake and elimination of orally administered fluid. These findings are likely to be of relevance when administering ORS in association with exercise.

  15. Nicotinic acid timed to feeding reverses tissue lipid accumulation and improves glucose control in obese Zucker rats[S].

    PubMed

    Kroon, Tobias; Baccega, Tania; Olsén, Arne; Gabrielsson, Johan; Oakes, Nicholas D

    2017-01-01

    Nicotinic acid (NiAc) is a potent inhibitor of lipolysis, acutely reducing plasma free fatty acid (FFA) concentrations. However, a major FFA rebound is seen during rapid NiAc washout, and sustained exposure is associated with tolerance development, with FFAs returning to pretreatment levels. Our aim was to find a rational NiAc dosing regimen that preserves FFA lowering, sufficient to reverse nonadipose tissue lipid accumulation and improve metabolic control, in obese Zucker rats. We compared feeding-period versus fasting-period NiAc dosing for 5 days: 12 h subcutaneous infusion (programmable, implantable mini-pumps) terminated by gradual withdrawal. It was found that NiAc timed to feeding decreased triglycerides in liver (-47%; P < 0.01) and heart (-38%; P < 0.05) and reduced plasma fructosamine versus vehicle. During oral glucose tolerance test, plasma FFA levels were reduced with amelioration of hyperglycemia and hypertriglyceridemia. Furthermore, timing NiAc to feeding resulted in a general downregulation of de novo lipogenesis (DNL) genes in liver. By contrast, NiAc timed to fasting did not reduce tissue lipids, ameliorate glucose intolerance or dyslipidemia, or alter hepatic DNL genes. In conclusion, NiAc dosing regimen has a major impact on metabolic control in obese Zucker rats. Specifically, a well-defined NiAc exposure, timed to feeding periods, profoundly improves the metabolic phenotype of this animal model. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  16. Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats.

    PubMed

    Jiang, Hua; Feng, Jueping; Du, Zhongxia; Zhen, Hui; Lin, Mei; Jia, Shaohui; Li, Tao; Huang, Xinyuan; Ostenson, Claes-Goran; Chen, Zhengwang

    2014-09-01

    Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin-eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function.

  17. Exercise Improves Glucose Disposal and Insulin Signaling in Pregnant Mice Fed a High Fat Diet

    PubMed Central

    Carter, Lindsay G; Ngo Tenlep, Sara Y; Woollett, Laura A; Pearson, Kevin J

    2016-01-01

    Objective Physical activity has been suggested as a non-pharmacological intervention that can be used to improve glucose homeostasis in women with gestational diabetes mellitus. The purpose of this study was to determine the effects of voluntary exercise on glucose tolerance and body composition in pregnant high fat diet fed mice. Methods Female mice were put on a standard diet or high fat diet for two weeks. The mice were then split into 4 groups; control standard diet fed, exercise standard diet fed, control high fat diet fed, and exercise high fat diet fed. Exercise mice had voluntary access to a running wheel in their home cage one week prior to mating, during mating, and throughout pregnancy. Glucose tolerance and body composition were measured during pregnancy. Akt levels were quantified in skeletal muscle and adipose tissue isolated from saline or insulin injected pregnant dams as a marker for insulin signaling. Results Consumption of the high fat diet led to significantly increased body weight, fat mass, and impaired glucose tolerance in control mice. However, voluntary running in the high fat diet fed dams significantly reduced weight gain and fat mass and ultimately improved glucose tolerance compared to control high fat diet fed dams. Further, body weight, fat mass, and glucose disposal in exercise high fat diet dams were indistinguishable from control dams fed the standard diet. High fat diet fed exercise dams also had significantly increased insulin stimulated phosphorylated Akt expression in adipose tissue, but not skeletal muscle, compared to control dams on high fat diet. Conclusion The use of voluntary exercise improves glucose homeostasis and body composition in pregnant female mice. Thus, future studies could investigate potential long-term health benefits in offspring born to obese exercising dams. PMID:26966635

  18. Peripheral activation of the Y2-receptor promotes secretion of GLP-1 and improves glucose tolerance

    PubMed Central

    Chandarana, Keval; Gelegen, Cigdem; Irvine, Elaine E.; Choudhury, Agharul I.; Amouyal, Chloé; Andreelli, Fabrizio; Withers, Dominic J.; Batterham, Rachel L.

    2013-01-01

    The effect of peptide tyrosine–tyrosine (PYY) on feeding is well established but currently its role in glucose homeostasis is poorly defined. Here we show in mice, that intraperitoneal (ip) injection of PYY3-36 or Y2R agonist improves nutrient-stimulated glucose tolerance and enhances insulin secretion; an effect blocked by peripheral, but not central, Y2R antagonist administration. Studies on isolated mouse islets revealed no direct effect of PYY3-36 on insulin secretion. Bariatric surgery in mice, enterogastric anastomosis (EGA), improved glucose tolerance in wild-type mice and increased circulating PYY and active GLP-1. In contrast, in Pyy-null mice, post-operative glucose tolerance and active GLP-1 levels were similar in EGA and sham-operated groups. PYY3-36 ip increased hepato-portal active GLP-1 plasma levels, an effect blocked by ip Y2R antagonist. Collectively, these data suggest that PYY3-36 therefore acting via peripheral Y2R increases hepato-portal active GLP-1 plasma levels and improves nutrient-stimulated glucose tolerance. PMID:24049729

  19. Targeted intestinal delivery of supersaturated itraconazole for improved oral absorption.

    PubMed

    Miller, Dave A; DiNunzio, James C; Yang, Wei; McGinity, James W; Williams, Robert O

    2008-06-01

    To investigate the use of Carbopol 974P as a stabilizing agent for supersaturated levels of itraconazole (ITZ) in neutral pH aqueous media and the resultant effects on oral absorption of ITZ. Carbopol 974P was incorporated into an EUDRAGIT L 100-55 carrier matrix at concentrations of 20% and 40% based on polymer weight with the aim of prolonging supersaturated ITZ release from the enteric matrix. Amorphous solid dispersions of ITZ in EUDRAGIT L 100-55 containing either 20% or 40% Carbopol 974P were produced by hot-melt extrusion (HME). Solid state analysis of these compositions was performed using differential scanning calorimetry and qualitative energy dispersive X-ray spectroscopy. Dissolution analysis was conducted using a pH change method. Oral absorption of ITZ was evaluated in male Sprague-Dawley rats. Solid state analysis demonstrated that the extruded compositions were entirely amorphous and homogenous with respect to drug distribution in the polymer matrix. Dissolution analysis revealed that the addition of Carbopol 974P to the EUDRAGIT L 100-55 carrier system functioned to prolong the release of supersaturated levels of ITZ from the EUDRAGIT L 100-55 matrix following an acidic-to-neutral pH transition. In vivo evaluation of ITZ absorption revealed that the addition of Carbopol 974P substantially reduced the absorption variability seen with the EUDRAGIT L 100-55 carrier system. In addition, the 20% Carbopol 974P formulation exhibited a five-fold improvement in absorption over our initially reported ITZ particulate dispersion compositions that limited supersaturation of ITZ primarily to the stomach. The results of this study strongly suggest that substantial improvements in oral antifungal therapy with ITZ can be achieved via intestinal targeting and polymeric stabilization of supersaturation.

  20. Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose.

    PubMed

    Yasunari, K; Kohno, M; Kano, H; Yokokawa, K; Minami, M; Yoshikawa, J

    1999-03-16

    To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs). Chronic high-glucose-medium (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [3H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.

  1. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.

    PubMed

    Vickers, Steven P; Cheetham, Sharon C; Headland, Katie R; Dickinson, Keith; Grempler, Rolf; Mayoux, Eric; Mark, Michael; Klein, Thomas

    2014-01-01

    The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.

  2. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet

    PubMed Central

    Vickers, Steven P; Cheetham, Sharon C; Headland, Katie R; Dickinson, Keith; Grempler, Rolf; Mayoux, Eric; Mark, Michael; Klein, Thomas

    2014-01-01

    The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes. PMID:25061325

  3. Doping Ag in ZnO Nanorods to Improve the Performance of Related Enzymatic Glucose Sensors.

    PubMed

    Zhou, Fan; Jing, Weixuan; Liu, Pengcheng; Han, Dejun; Jiang, Zhuangde; Wei, Zhengying

    2017-09-27

    In this paper, the performance of a zinc oxide (ZnO) nanorod-based enzymatic glucose sensor was enhanced with silver (Ag)-doped ZnO (ZnO-Ag) nanorods. The effect of the doped Ag on the surface morphologies, wettability, and electron transfer capability of the ZnO-Ag nanorods, as well as the catalytic character of glucose oxidase (GOx) and the performance of the glucose sensor was investigated. The results indicate that the doped Ag slightly weakens the surface roughness and hydrophilicity of the ZnO-Ag nanorods, but remarkably increases their electron transfer ability and enhances the catalytic character of GOx. Consequently, the combined effects of the above influencing factors lead to a notable improvement of the performance of the glucose sensor, that is, the sensitivity increases and the detection limit decreases. The optimal amount of the doped Ag is determined to be 2 mM, and the corresponding glucose sensor exhibits a sensitivity of 3.85 μA/(mM·cm²), detection limit of 1.5 μM, linear range of 1.5 × 10(-3)-6.5 mM, and Michaelis-Menten constant of 3.87 mM. Moreover, the glucose sensor shows excellent selectivity to urea, ascorbic acid, and uric acid, in addition to displaying good storage stability. These results demonstrate that ZnO-Ag nanorods are promising matrix materials for the construction of other enzymatic biosensors.

  4. California's state oral health infrastructure: opportunities for improvement and funding.

    PubMed

    Diringer, Joel; Phipps, Kathy R

    2012-01-01

    California has virtually no statewide dental public health infrastructure leaving the state without leadership, a surveillance program, an oral health plan, oral health promotion and disease prevention programs, and federal funding. Based on a literature review and interviews with 15 oral health officials nationally, the paper recommends hiring a state dental director with public health experience, developing a state oral health plan, and seeking federal and private funding to support an office of oral health.

  5. Gestational diabetes alters the fetal heart rate variability during an oral glucose tolerance test: a fetal magnetocardiography study.

    PubMed

    Fehlert, E; Willmann, K; Fritsche, L; Linder, K; Mat-Husin, H; Schleger, F; Weiss, M; Kiefer-Schmidt, I; Brucker, S; Häring, H-U; Preissl, H; Fritsche, A

    2016-12-28

    Gestational diabetes mellitus (GDM) potentially harms the child before birth. We previously found GDM to be associated with developmental changes in the central nervous system. We now hypothesise that GDM may also impact on the fetal autonomic nervous system under metabolic stress like an oral glucose tolerance test (OGTT). We measured heart rate variability (HRV) of mothers and fetuses during a three-point OGTT using fetal magnetocardiography (fMCG). Measurements were performed in the fMEG Centre in Tübingen. After exclusion of 23 participants, 13 pregnant women with GDM and 36 pregnant women with normal glucose tolerance were examined. All women underwent the same examination setting with OGTT during which fMCG was recorded three times. Parameters of heart rate variability were measured. Compared with mothers with normal glucose regulation, mothers with GDM showed increased heart rate but no significant differences of maternal HRV. In contrast, HRV in fetuses of mothers with GDM differed from those in the metabolically healthy group regarding standard deviation normal to normal beat (SDNN) (P = 0.012), low-frequency band (P = 0.008) and high-frequency band (P = 0.031). These HRV parameters exhibit a decrease only in GDM fetuses during the second hour of the OGTT. These results show an altered response of the fetal autonomic nervous system to metabolic stress in GDM-complicated pregnancies. Hence, disturbances in maternal glucose metabolism might not only impact on the central nervous system of the fetus but may also affect the fetal autonomic nervous system. Metabolic stress reveals a different response of fetal autonomic nervous system in GDM-complicated pregnancies. © 2016 Royal College of Obstetricians and Gynaecologists.

  6. Dietary substitution of medium-chain triglycerides improves insulin-mediated glucose metabolism in NIDDM subjects.

    PubMed

    Eckel, R H; Hanson, A S; Chen, A Y; Berman, J N; Yost, T J; Brass, E P

    1992-05-01

    Dietary medium-chain triglycerides (MCT) may improve insulin-mediated glucose metabolism. To examine this possibility, 10 non-insulin-dependent diabetes mellitus (NIDDM) patients, 4 hypertriglyceridemic, and 6 normotriglyceridemic nondiabetic control subjects were examined with a 5-day cross-over design, in which the short-term metabolic effects of a 40% fat diet containing 77.5% of fat calories as MCT were compared with an isocaloric long-chain triglyceride-containing diet. In diabetic patients, MCT failed to alter fasting serum glucose concentrations but reduced preprandial glycemic excursions by 45% (F = 7.9, P less than 0.01). On MCT, the amount of glucose needed to maintain euglycemia during an intravenous insulin infusion was increased in diabetic subjects by 30%, in hypertriglyceridemic subjects by 30%, and in normotriglyceridemic control subjects by 17%. MCT increased mean +/- SE insulin-mediated glucose disposal (4.52 +/- 0.56 vs. 2.89 +/- 0.21 mg.kg-1.min-1; n = 3, P less than 0.05) but failed to alter basal glucose metabolism or insulin-mediated suppression of hepatic glucose output. Metabolic responses to MCT were observed independent of sulfonylurea therapy or severity of fasting hyperglycemia. No change in fasting serum insulin or triglyceride concentrations were seen with MCT administration. Although MCT increased mean fasting serum beta-hydroxybutyrate levels from 0.10 +/- 0.03 to 0.26 +/- 0.06 mM (P less than 0.05) in normotriglyceridemic nondiabetic subjects, no change was seen in diabetic patients. Thus, MCT-containing diets increased insulin-mediated glucose metabolism in both diabetic patients and nondiabetic subjects. In diabetic subjects, this effect appears to be mediated by increases in insulin-mediated glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    SciTech Connect

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  8. Efficacy of standard glucose-based and reduced-osmolarity maltodextrin-based oral rehydration solutions: effect of sugar malabsorption.

    PubMed

    el-Mougi, M; Hendawi, A; Koura, H; Hegazi, E; Fontaine, O; Pierce, N F

    1996-01-01

    Previously we reported that standard oral rehydration salts (ORS) solution is not as effective as a reduced-osmolarity glucose-based ORS for the treatment of children with acute noncholera diarrhoea: with standard ORS the diarrhoea lasts longer, stool output is greater, serum sodium is higher, and there is more need for supplemental intravenous infusion. We studied a reduced-osmolarity maltodextrin (MD)-based ORS to determine whether it had similar benefits, and also the effect of sugar malabsorption on the efficacy of standard and MD-based ORS. A total of 90 boys aged 3-24 months with acute noncholera diarrhoea and moderate dehydration were randomly assigned to either standard ORS (glucose 20 g/l, osmolarity 311 mmol/l) or MD-ORS (MD 50 g/l, osmolarity 227 mmol/l). There were no differences in treatment results. Some 46% of subjects had a high total stool output (> 300 g/kg), which was unrelated to the type of ORS given. High stool output was significantly associated with a longer duration of diarrhoea (33 vs. 15 hours; P < 0.001), a persistently elevated serum sodium (149 vs. 144 mmol/l at 24 h; P < 0.02), the need for intravenous infusion (11/41 vs. 0/48; P < 0.002), and an increase in faecal reducing substances (10.8 vs. 3.4 g/l at 24 h; P < 0.001). We conclude that some children given standard ORS develop osmotic diarrhoea owing to the combined effect of transient sugar malabsorption and slight hypertonicity of the ORS. Earlier studies show that this adverse outcome can largely be avoided when extra water is given in reduced-osmolarity glucose-based ORS. Reduced osmolarity has no benefit, however, when glucose is replaced by maltodextrin, probably because the sugars released by hydrolysis of MD, when malabsorbed, raise the intraluminal osmolarity to equal or exceed that of standard ORS. Thus, reduced-osmolarity glucose-based ORS is superior to both standard ORS and reduced-osmolarity solutions based on maltodextrin and probably other complex carbohydrates

  9. Efficacy of standard glucose-based and reduced-osmolarity maltodextrin-based oral rehydration solutions: effect of sugar malabsorption.

    PubMed Central

    el-Mougi, M.; Hendawi, A.; Koura, H.; Hegazi, E.; Fontaine, O.; Pierce, N. F.

    1996-01-01

    Previously we reported that standard oral rehydration salts (ORS) solution is not as effective as a reduced-osmolarity glucose-based ORS for the treatment of children with acute noncholera diarrhoea: with standard ORS the diarrhoea lasts longer, stool output is greater, serum sodium is higher, and there is more need for supplemental intravenous infusion. We studied a reduced-osmolarity maltodextrin (MD)-based ORS to determine whether it had similar benefits, and also the effect of sugar malabsorption on the efficacy of standard and MD-based ORS. A total of 90 boys aged 3-24 months with acute noncholera diarrhoea and moderate dehydration were randomly assigned to either standard ORS (glucose 20 g/l, osmolarity 311 mmol/l) or MD-ORS (MD 50 g/l, osmolarity 227 mmol/l). There were no differences in treatment results. Some 46% of subjects had a high total stool output (> 300 g/kg), which was unrelated to the type of ORS given. High stool output was significantly associated with a longer duration of diarrhoea (33 vs. 15 hours; P < 0.001), a persistently elevated serum sodium (149 vs. 144 mmol/l at 24 h; P < 0.02), the need for intravenous infusion (11/41 vs. 0/48; P < 0.002), and an increase in faecal reducing substances (10.8 vs. 3.4 g/l at 24 h; P < 0.001). We conclude that some children given standard ORS develop osmotic diarrhoea owing to the combined effect of transient sugar malabsorption and slight hypertonicity of the ORS. Earlier studies show that this adverse outcome can largely be avoided when extra water is given in reduced-osmolarity glucose-based ORS. Reduced osmolarity has no benefit, however, when glucose is replaced by maltodextrin, probably because the sugars released by hydrolysis of MD, when malabsorbed, raise the intraluminal osmolarity to equal or exceed that of standard ORS. Thus, reduced-osmolarity glucose-based ORS is superior to both standard ORS and reduced-osmolarity solutions based on maltodextrin and probably other complex carbohydrates

  10. Chromium yeast supplementation improves fasting plasma glucose and LDL-cholesterol in streptozotocin-induced diabetic rats.

    PubMed

    Lai, Ming-Hoang; Chen, Ya-Yen; Cheng, Hsing-Hsien

    2006-11-01

    Chromium yeast supplementation has been studied for its ability to improve carbohydrate and lipid abnormalities. There have been some earlier literature-reported studies involving chromium supplementation amongst patients suffering diabetes, but the results would appear to be somewhat varied. Forty male Wistar rats (ten weeks old, 300 g in average body mass) were divided into one of four groups, namely (i) controls; (ii) controls treated with chromium yeast; (iii) diabetic controls; and (iv) diabetic rats treated with chromium yeast. In the present investigation, the effect of a four-week oral administration of chromium yeast (600 microg of Cr/kg body mass/day, by gavage) upon the glucose and lipid metabolism in streptozotocin (STZ)-induced diabetic rats was assessed. Supplemental Cr yeast decreased the fasting blood glucose amongst the STZ-diabetic rats. No significant difference was observed in plasma fructosamine levels of rats treated with chromium yeast compared to control rats. Supplemental Cr yeast did decrease the plasma low-density lipoprotein (LDL)-cholesterol level for the STZ-diabetic rats as compared to controls. We noted no significant effect of chromium supplementation upon plasma high-density lipoprotein (HDL)-cholesterol or triglycerides compared to controls. Treatment with chromium yeast significantly increased the blood and urine chromium levels for both the diabetic and normal rats compared to respective control groups. The results of these studies suggest that Cr yeast decreased the fasting blood glucose and LDL-cholesterol levels in STZ-induced diabetic rats. This raises the possibility that Cr yeast supplementation can be considered to improve carbohydrate and lipid metabolism amongst human patients featuring type 2 diabetes mellitus.

  11. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet.

    PubMed

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling.

  12. Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia.

    PubMed

    Khalifi, Saeedeh; Rahimipour, Ali; Jeddi, Sajad; Ghanbari, Mahboubeh; Kazerouni, Faranak; Ghasemi, Asghar

    2015-01-30

    Reduction in nitric oxide (NO) production and bioavailability contribute to the pathogenesis of type 2 diabetes. Administration of nitrate has strong NO-like outcomes in both animals and humans. In this study, we examined the effects of dietary nitrate on glucose tolerance and lipid profile in type 2 diabetic rats. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Thirty-two male Wistar rats were divided into 4 groups: controls (C), control+nitrate (CN), diabetes (D), and diabetes+nitrate (DN). For 8 weeks, the CN and DN groups consumed sodium nitrate (100 mg/L in drinking water) while the C and D groups consumed tap water. Serum nitrate+nitrite (NOx), glucose, lipid profile, total antioxidant capacity (TAC), and catalase (CAT) activity were measured before and at the end of the study. Systolic blood pressure (SBP) was measured every 10 days. Intravenous glucose tolerance test (IVGTT) was performed at the end of the study. Serum NOx decreased in diabetic rats and dietary nitrate restored it to normal values. Increases in serum glucose levels was significantly lower in the DN group compared to the D group (24.1% vs. 90.2%; p < 0.05). Nitrate therapy in diabetic rats significantly improved lipid profile, glucose tolerance (AUC: 20264 ± 659 vs. 17923 ± 523; p < 0.05 for D and DN groups respectively) and restored elevated SBP to normal values. Diabetic rats had lower TAC and CAT activity and dietary nitrate restored these to normal status. In conclusion, dietary nitrate prevented increase in SBP and serum glucose, improved glucose tolerance and restored dyslipidemia in an animal model of hyperglycemia.

  13. The midwifery initiated oral health-dental service protocol: an intervention to improve oral health outcomes for pregnant women.

    PubMed

    Johnson, Maree; George, Ajesh; Dahlen, Hannah; Ajwani, Shilpi; Bhole, Sameer; Blinkhorn, Anthony; Ellis, Sharon; Yeo, Anthony

    2015-01-15

    Evidence is emerging that women's poor oral health and health practices during pregnancy are associated with poor oral health in their children and potentially an increased risk of pre-term or low-birth weight infants. The Midwifery Initiated Oral Health-Dental Service (MIOH-DS) trial is a three arm multicentre randomised controlled trial which will recruit women from three metropolitan hospitals aimed at improving women's oral health and service access and indirectly reducing perinatal morbidity. All three arms of the trial will deliver oral health promotion material, although a midwife oral assessment and referral to private/public/health fund dental services pathway (Intervention Group 1) and the midwife oral assessment and referral to local free public dental services pathway (Intervention Group 2) will be compared to the control group of oral health promotional material only. Midwives will undergo specific oral health education and competency testing to undertake this novel intervention. This efficacy trial will promote a new partnership between midwives and dentists focused on enhancing the oral health of women and their infants. Should the intervention be found effective, this intervention, with existing on-line educational program for midwives, can be easily transferred into practice for large metropolitan health services within and beyond Australia. Further cost-benefit analysis is proposed to inform national health policy. Australian New Zealand Clinical Trials Registry ACTRN12612001271897.

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

    PubMed

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

    2017-03-01

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

  15. A Blend of Phellodendron and Crape Myrtle Improves Glucose Tolerance in Exercise-Trained Men

    PubMed Central

    Canale, Robert E.; Farney, Tyler M.; McCarthy, Cameron G.; Bloomer, Richard J.

    2011-01-01

    Background: The purpose of this study was to investigate the acute effects of a nutritional supplement containing a proprietary blend of Phellodendron and Crape Myrtle on serum glucose and insulin in response to a modified oral glucose tolerance test (OGTT). Methods: Using a randomized, double-blind, cross-over design, 10 exercise-trained, non-diabetic men reported to the lab in a 10 hour fasted state, on two different mornings separated by 1–2 weeks, and were subjected to an OGTT by ingesting a 75 gram dextrose solution. Fifteen minutes prior to the OGTT subjects ingested either a dietary supplement containing a blend of Phellodendron and Crape Myrtle (SUPP) or a placebo (PLA). Blood samples were collected before ingestion of the SUPP or PLA and at 15, 30, 45, 60, and 75 minutes post-ingestion of the dextrose load. Samples were analyzed for serum glucose and insulin. Results: In relation to serum glucose, a condition effect was noted (P = 0.01), with values lower for SUPP compared to PLA. In relation to serum insulin, a trend for a condition effect was noted (P = 0.06), with values lower for SUPP compared to PLA. Conclusion: These findings indicate that acute ingestion of a dietary supplement containing a blend of Phellodendron and Crape Myrtle can lower the serum glucose response to a modified OGTT, while resulting in a non-significant attenuation in insulin response. These data are specific to a small sample of exercise-trained, non-diabetic men. PMID:23946660

  16. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice.

    PubMed

    Ferron, Mathieu; McKee, Marc D; Levine, Robert L; Ducy, Patricia; Karsenty, Gérard

    2012-02-01

    The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30 ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both β-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes.

  17. Intermittent cold exposure improves glucose homeostasis associated with brown and white adipose tissues in mice

    PubMed Central

    Wang, Tse-Yao; Liu, Cuiqing; Wang, Aixia; Sun, Qinghua

    2015-01-01

    Aims The discovery of different shades of fat has been implicated in the pathogenesis of obesity-related metabolic disorders. However, the effects of early and intermittent exposure to cold temperature on systemic metabolic changes in adult life remain unclear. Main methods To elucidate the impact of cold temperature exposure on metabolic function of adipose tissues, we investigated the glucose homeostasis, activation of brown adipose tissue (BAT) and “browning” of white adipose tissue (WAT) in mice in response to intermittent cold exposure. Mice were exposed to 4 °C, 2 hours per day and 5 days per week, for 14 weeks. Glucose homeostasis was tested via intraperitoneal glucose tolerance test and insulin tolerance test; body fat mass was evaluated using in vivo magnetic resonance imaging; BAT activity was detected primarily by positron emission tomography/computed tomography; and WAT “browning” was evaluated using immunohistochemistry. Key findings Our results showed that 14-week cold exposure improved glucose tolerance and enhanced insulin sensitivity, reduced the relative weights of epididymal and retroperitoneal WAT, increased expressions of UCP1 and PGC1α in subcutaneous adipose tissue. Significance Intermittent exposure to cold temperature in early life may improve systemic glucose homeostasis and induce WAT “browning”, suggesting that ambient cold temperature exposure may serve as a promising intervention to metabolic disorders. PMID:26281919

  18. The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetes.

    PubMed

    Luzio, S D; Dunseath, G; Lockett, A; Broke-Smith, T P; New, R R; Owens, D R

    2010-01-01

    Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m(2), haemoglobin A(1c) (HbA(1c)) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280-330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC(0-6 h) (910 +/- 270 vs. 472 +/- 245 pmol h/L; 950 +/- 446 vs. 433 +/- 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA(1c), weight and triglycerides were observed. Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations.

  19. Exercise training improves cardiovascular autonomic modulation in response to glucose ingestion in obese adults with and without type 2 diabetes mellitus.

    PubMed

    Goulopoulou, Styliani; Baynard, Tracy; Franklin, Ruth M; Fernhall, Bo; Carhart, Robert; Weinstock, Ruth; Kanaley, Jill A

    2010-06-01

    This study examined the effect of aerobic exercise training on vagal and sympathetic influences on the modulations of heart rate and systolic blood pressure in response to an oral glucose load in obese individuals with and without type 2 diabetes mellitus (T2D). Beat-to-beat arterial pressure and continuous electrocardiogram were measured after a 12-hour overnight fast and in response to glucose ingestion (75 g dextrose) in obese subjects with (T2D group, n = 23) and without (OB group, n = 36) T2D before and after 16 weeks of aerobic exercise training at moderate intensity. Autonomic modulation was assessed using spectral analysis of systolic blood pressure variability (BPV), heart rate variability (HRV), and analysis of baroreflex sensitivity (BRS). Glucose ingestion significantly increased low-frequency (LF(SBP)), low-frequency HRV (LF(RRI)), and the ratio of low- to high-frequency components of HRV (LF(RRI)/HF(RRI)), and decreased the high-frequency power (HF(RRI)) (P < .05). Exercise training increased LF(RRI) and LF(RRI)/HF(RRI) responses, and reduced HF(RRI) and LF(SBP) to glucose ingestion in both groups (P < .05), but increased fasted BRS in the OB group only (P < .05); glucose intake had no effect on BRS (P > .05). In conclusion, a 16-week exercise training program improved cardiac autonomic modulation in response to an oral glucose load in obese adults, independently of diabetes status, and in the absence of remarkable changes in body weight, body composition, fitness level, and glycemic control.

  20. Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice.

    PubMed

    Iffiú-Soltész, Zsuzsa; Wanecq, Estelle; Lomba, Almudena; Portillo, Maria P; Pellati, Federica; Szöko, Eva; Bour, Sandy; Woodley, John; Milagro, Fermin I; Alfredo Martinez, J; Valet, Philippe; Carpéné, Christian

    2010-04-01

    Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.

  1. A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or β-cell mass in NZO mice

    PubMed Central

    Lamont, B J; Waters, M F; Andrikopoulos, S

    2016-01-01

    Background/Objectives: Dietary guidelines for the past 20 years have recommended that dietary fat should be minimized. In contrast, recent studies have suggested that there could be some potential benefits for reducing carbohydrate intake in favor of increased fat. It has also been suggested that low-carbohydrate diets be recommended for people with type 2 diabetes. However, whether such diets can improve glycemic control will likely depend on their ability to improve β-cell function, which has not been studied. The objective of the study was to assess whether a low-carbohydrate and therefore high-fat diet (LCHFD) is beneficial for improving the endogenous insulin secretory response to glucose in prediabetic New Zealand Obese (NZO) mice. Methods: NZO mice were maintained on either standard rodent chow or an LCHFD from 6 to 15 weeks of age. Body weight, food intake and blood glucose were assessed weekly. Blood glucose and insulin levels were also assessed after fasting and re-feeding and during an oral glucose tolerance test. The capacity of pancreatic β-cells to secrete insulin was assessed in vivo with an intravenous glucose tolerance test. β-Cell mass was assessed in histological sections of pancreata collected at the end of the study. Results: In NZO mice, an LCHFD reduced plasma triglycerides (P=0.001) but increased weight gain (P<0.0001), adipose tissue mass (P=0.0015), high-density lipoprotein cholesterol (P=0.044) and exacerbated glucose intolerance (P=0.013). Although fasting insulin levels tended to be higher (P=0.08), insulin secretory function in LCHFD-fed mice was not improved (P=0.93) nor was β-cell mass (P=0.75). Conclusions: An LCHFD is unlikely to be of benefit for preventing the decline in β-cell function associated with the progression of hyperglycemia in type 2 diabetes. PMID:26878317

  2. A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or β-cell mass in NZO mice.

    PubMed

    Lamont, B J; Waters, M F; Andrikopoulos, S

    2016-02-15

    Dietary guidelines for the past 20 years have recommended that dietary fat should be minimized. In contrast, recent studies have suggested that there could be some potential benefits for reducing carbohydrate intake in favor of increased fat. It has also been suggested that low-carbohydrate diets be recommended for people with type 2 diabetes. However, whether such diets can improve glycemic control will likely depend on their ability to improve β-cell function, which has not been studied. The objective of the study was to assess whether a low-carbohydrate and therefore high-fat diet (LCHFD) is beneficial for improving the endogenous insulin secretory response to glucose in prediabetic New Zealand Obese (NZO) mice. NZO mice were maintained on either standard rodent chow or an LCHFD from 6 to 15 weeks of age. Body weight, food intake and blood glucose were assessed weekly. Blood glucose and insulin levels were also assessed after fasting and re-feeding and during an oral glucose tolerance test. The capacity of pancreatic β-cells to secrete insulin was assessed in vivo with an intravenous glucose tolerance test. β-Cell mass was assessed in histological sections of pancreata collected at the end of the study. In NZO mice, an LCHFD reduced plasma triglycerides (P=0.001) but increased weight gain (P<0.0001), adipose tissue mass (P=0.0015), high-density lipoprotein cholesterol (P=0.044) and exacerbated glucose intolerance (P=0.013). Although fasting insulin levels tended to be higher (P=0.08), insulin secretory function in LCHFD-fed mice was not improved (P=0.93) nor was β-cell mass (P=0.75). An LCHFD is unlikely to be of benefit for preventing the decline in β-cell function associated with the progression of hyperglycemia in type 2 diabetes.

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

    PubMed

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

    2017-04-01

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

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

    PubMed Central

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

    2017-01-01

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

  5. Long-Term Improvement in Glucose Control and Counterregulation by Islet Transplantation for Type 1 Diabetes.

    PubMed

    Rickels, Michael R; Peleckis, Amy J; Markmann, Eileen; Dalton-Bakes, Cornelia; Kong, Stephanie M; Teff, Karen L; Naji, Ali

    2016-11-01

    Islet transplantation has been shown to improve glucose counterregulation and hypoglycemia symptom recognition in patients with type 1 diabetes (T1D) complicated by severe hypoglycemia episodes and symptom unawareness, but long-term data are lacking. To assess the long-term durability of glucose counterregulation and hypoglycemia symptom responses 18 months after intrahepatic islet transplantation and associated measures of glycemic control during a 24-month follow-up period. Ten patients with T1D disease duration of approximately 27 years were studied longitudinally before and 6 and 18 months after transplant in the Clinical & Translational Research Center of the University of Pennsylvania and were compared to 10 nondiabetic control subjects. All 10 patients underwent intrahepatic islet transplantation according to the CIT07 protocol at the Hospital of the University of Pennsylvania. Counterregulatory hormone, endogenous glucose production, and autonomic symptom responses derived from stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-(2)H2-glucose. Near-normal glycemia (HbA1c ≤ 6.5%; time 70-180 mg/dL ≥ 95%) was maintained for 24 months in all patients, with one returning to low-dose insulin therapy. In response to insulin-induced hypoglycemia, glucagon secretion was incompletely restored at 6 and 18 months, epinephrine was improved at 6 months and normalized at 18 months, and endogenous glucose production and symptoms, absent before, were normalized at 6 and 18 months after transplant. In patients with T1D experiencing problematic hypoglycemia, intrahepatic islet transplantation can lead to long-term improvement of glucose counterregulation and hypoglycemia symptom recognition, physiological effects that likely contribute to glycemic stability after transplant.

  6. Bis-Pyrano Prenyl Isoflavone Improves Glucose Homeostasis by Inhibiting Dipeptidyl Peptidase-4 in Hyperglycemic Rats.

    PubMed

    Altenhofen, Delsi; da Luz, Gabrielle; Frederico, Marisa Jádna Silva; Venzke, Dalila; Brich, Mayara; Vigil, Silvana; Fröde, Tania Silvia; Linares, Carlos Eduardo Blanco; Pizzolatti, Moacir Geraldo; Silva, Fátima Regina Mena Barreto

    2017-01-01

    Isoflavones widely distributed in plants prevent diabetes. This study investigated the in vivo and in vitro effect of 3',4'-dihydroxy-6″,6″,6″',6″'-tetramethylbis(pyrano[2″,3″:5,6::2″',3″':7,8]isoflavone (bis-pyrano prenyl isoflavone) on glucose homeostasis in hyperglycemic rats. The ethyl acetate fraction from aerial parts of Polygala molluginifolia that contain isoflavones was assayed on glucose tolerance, on in vitro maltase activity and on protein glycation. The isoflavone bis-pyrano prenyl isolated from this fraction was investigated on glucose homeostasis. The in vivo action of the isoflavone exhibits an anti-hyperglycemic effect by improving glucose tolerance, augmenting the liver glycogen, inhibiting maltase activity, and stimulating glucagon-like peptide-1 (GLP-1) and insulin secretion. The in vitro isoflavone inhibits dipeptidyl peptidase-4 (DPP-4) activity since the glucose tolerance was improved in the presence of the isoflavone as much as sitagliptin, an inhibitor of DPP-4. However, the co-incubation with isoflavone and sitagliptin exhibited an additive anti-hyperglycemic action. The isoflavone increased the GLP-1 faster than the positive hyperglycemic group, which shows that the intestine is a potential target. Thus, to clarify the main site of action in which isoflavone improves glucose balance, the in vitro mechanism of action of this compound was tested in intestine using calcium influx as a trigger for the signal pathways for GLP-1 secretion. The isoflavone stimulates calcium influx in intestine and its mechanism involves voltage-dependent calcium channels, phospholipase C, protein kinase C, and stored calcium contributing for GLP-1 secretion. In conclusion, the isoflavone regulates glycaemia by acting mainly in a serum target, the DPP-4 inhibitor. Furthermore, the long-term effect of isoflavone prevents protein glycation. J. Cell. Biochem. 118: 92-103, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice.

    PubMed

    Miranda, Cristobal L; Elias, Valerie D; Hay, Joshua J; Choi, Jaewoo; Reed, Ralph L; Stevens, Jan F

    2016-06-01

    Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain. Plasma levels of glucose, total triglycerides, total cholesterol, and MCP-1 were significantly decreased in mice on the 60 mg/kg/day treatment regimen. Treatment with XN at 60 mg/kg/day resulted in reduced plasma LDL-cholesterol (LDL-C), IL-6, insulin and leptin levels by 80%, 78%, 42%, and 41%, respectively, compared to the vehicle control group. Proprotein Convertase Subtilisin Kexin 9 (PCSK-9) levels were 44% lower in the 60 mg/kg dose group compared to the vehicle control group (p ≤ 0.05) which may account for the LDL-C lowering activity of XN. Our results show that oral administration of XN improves markers of systemic inflammation and metabolic syndrome in diet-induced obese C57BL/6J mice.

  8. Detection of Abnormal Glucose Tolerance in Africans Is Improved by Combining A1C With Fasting Glucose: The Africans in America Study

    PubMed Central

    Thoreson, Caroline K.; O'Connor, Michelle Y.; Ricks, Madia; Chung, Stephanie T.; Tulloch-Reid, Marshall K.; Lozier, Jay N.; Sacks, David B.

    2015-01-01

    OBJECTIVE Abnormal glucose tolerance is rising in sub-Saharan Africa. Hemoglobin A1c by itself and in combination with fasting plasma glucose (FPG) is used to diagnose abnormal glucose tolerance. The diagnostic ability of A1C in Africans with heterozygous variant hemoglobin, such as sickle cell trait or hemoglobin C trait, has not been rigorously evaluated. In U.S.-based Africans, we determined by hemoglobin status the sensitivities of 1) FPG ≥5.6 mmol/L, 2) A1C ≥ 5.7% (39 mmol/mol), and 3) FPG combined with A1C (FPG ≥5.6 mmol/L and/or A1C ≥5.7% [39 mmol/mol]) for the detection of abnormal glucose tolerance. RESEARCH DESIGN AND METHODS An oral glucose tolerance test (OGTT) was performed in 216 African immigrants (68% male, age 37 ± 10 years [mean ± SD], range 20–64 years). Abnormal glucose tolerance was defined as 2-h glucose ≥7.8 mmol/L. RESULTS Variant hemoglobin was identified in 21% (46 of 216). Abnormal glucose tolerance occurred in 33% (72 of 216). When determining abnormal glucose tolerance from the OGTT (2-h glucose ≥7.8 mmol/L), sensitivities of FPG for the total, normal, and variant hemoglobin groups were 32%, 32%, and 33%, respectively. Sensitivities for A1C were 53%, 54%, and 47%. For FPG and A1C combined, sensitivities were 64%, 63%, and 67%. Sensitivities for FPG and A1C and the combination did not vary by hemoglobin status (all P > 0.6). For the entire cohort, sensitivity was higher for A1C than FPG and for both tests combined than for either test alone (all P values ≤ 0.01). CONCLUSIONS No significant difference in sensitivity of A1C by variant hemoglobin status was detected. For the diagnosis of abnormal glucose tolerance in Africans, the sensitivity of A1C combined with FPG is significantly superior to either test alone. PMID:25338926

  9. Detection of abnormal glucose tolerance in Africans is improved by combining A1C with fasting glucose: the Africans in America Study.

    PubMed

    Sumner, Anne E; Thoreson, Caroline K; O'Connor, Michelle Y; Ricks, Madia; Chung, Stephanie T; Tulloch-Reid, Marshall K; Lozier, Jay N; Sacks, David B

    2015-02-01

    Abnormal glucose tolerance is rising in sub-Saharan Africa. Hemoglobin A1c by itself and in combination with fasting plasma glucose (FPG) is used to diagnose abnormal glucose tolerance. The diagnostic ability of A1C in Africans with heterozygous variant hemoglobin, such as sickle cell trait or hemoglobin C trait, has not been rigorously evaluated. In U.S.-based Africans, we determined by hemoglobin status the sensitivities of 1) FPG ≥5.6 mmol/L, 2) A1C ≥ 5.7% (39 mmol/mol), and 3) FPG combined with A1C (FPG ≥5.6 mmol/L and/or A1C ≥5.7% [39 mmol/mol]) for the detection of abnormal glucose tolerance. An oral glucose tolerance test (OGTT) was performed in 216 African immigrants (68% male, age 37 ± 10 years [mean ± SD], range 20-64 years). Abnormal glucose tolerance was defined as 2-h glucose ≥7.8 mmol/L. Variant hemoglobin was identified in 21% (46 of 216). Abnormal glucose tolerance occurred in 33% (72 of 216). When determining abnormal glucose tolerance from the OGTT (2-h glucose ≥7.8 mmol/L), sensitivities of FPG for the total, normal, and variant hemoglobin groups were 32%, 32%, and 33%, respectively. Sensitivities for A1C were 53%, 54%, and 47%. For FPG and A1C combined, sensitivities were 64%, 63%, and 67%. Sensitivities for FPG and A1C and the combination did not vary by hemoglobin status (all P > 0.6). For the entire cohort, sensitivity was higher for A1C than FPG and for both tests combined than for either test alone (all P values ≤ 0.01). No significant difference in sensitivity of A1C by variant hemoglobin status was detected. For the diagnosis of abnormal glucose tolerance in Africans, the sensitivity of A1C combined with FPG is significantly superior to either test alone. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure

    PubMed Central

    Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.

    2013-01-01

    Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM

  11. Glucose tolerance factor extracted from yeast: oral insulin-mimetic and insulin-potentiating agent: in vivo and in vitro studies.

    PubMed

    Weksler-Zangen, Sarah; Mizrahi, Tal; Raz, Itamar; Mirsky, Nitsa

    2012-09-01

    In search for an effective oral treatment for diabetes, we examined the capacity of glucose tolerance factor (GTF) extracted from yeast and administered orally to reduce hyperglycaemia in rat models exhibiting insulin deficiency. The cellular effect of GTF on the insulin signalling pathway was investigated in vitro. GTF (oral bolus), insulin (intraperitoneal) or their combination was administered to streptozotocin-diabetic (STZ) or hyperglycaemic Cohen diabetic-sensitive (hyp-CDs) rats. Blood glucose (BG) and insulin levels were measured in the postprandial (PP) state and during an oral glucose tolerance test. Deoxy-glucose transport and insulin signal transduction were assessed in 3T3-L1 adipocytes and myoblasts incubated with the GTF. Low dose of insulin produced a 34 and 12·5 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. GTF induced a 33 and 17 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. When combined with insulin, a respective decrease (58 and 42 %) in BG levels was observed, suggesting a partially additive (hyp-CDs) or synergistic (STZ rats) effect of the GTF and insulin. GTF did not induce insulin secretion in hyp-CDs rats, yet it lowered their BG levels, proposing an effect on glucose clearance by peripheral tissues. GTF induced a dose-dependent increase in deoxy-glucose transport into myoblasts and fat cells similar to insulin, while the combined treatment resulted in augmented transport rate. GTF induced a dose- and time-dependent phosphorylation of insulin receptor substrate 1, Akt and mitogen-activated protein kinase independent of insulin receptor phosphorylation. GTF exerts remarkable insulin-mimetic and insulin-potentiating effects, both in vivo and in vitro. It produces an insulin-like effect by acting on cellular signals downstream of the insulin receptor. These results demonstrate a potential source for a novel oral medication for diabetes.

  12. Cordyceps sinensis Oral Liquid Inhibits Damage Induced by Oxygen and Glucose Deprivation in SH-SY5Y Cells.

    PubMed

    Zou, Ying-Xin; Liu, Yu-Xiang; Ruan, Ming-Hua; Zhou, Yi; Wang, Jia-Chun; Chu, Zhi-Yong

    2016-01-01

    Cordyceps sinensis has been used in traditional Chinese medicine for thousands of years. It has been demonstrated to have a variety of biological activities, and an extract of it has been demonstrated to possess a protective effect in occlusion-induced focal cerebral ischemia of the middle cerebral artery in rats. It could be explored as an agent for treatment of ischemic stroke, and the mechanisms need to be studied further. The study intended to investigate the protective effects of the Cordyceps sinensis oral liquid (CSOL) against damage induced by oxygen and glucose deprivation (OGD) in SH-SY5Y cells. DESIGN • The research team designed an in vitro study. The study occurred at the Naval Medical Research Institute in Shanghai, China. SH-SY5Y cells were exposed to CSOL in doses of 0.01, 0.03, 0.10, 0.30, and 1.00 mg/mL, creating 5 intervention groups. The OGD condition was induced by transfer of the cells from high-glucose Dulbecco's Modified Eagle's medium (DMEM) in a box gassed with air containing 5% CO2 to glucose-free DMEM in a box gassed with 94% N2, 5% CO2, and 1% O2. Like the cells for the interventions groups, the cells for a model group were cultured with high-glucose DMEM and were transferred to the OGD, but they received no dose of COSL. Cells in a control group were cultured with high-glucose DMEM, were not transferred to the OGD condition, and did not receive any dose of COSL. Cell viability was assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The apoptosis and the mitochondrial membrane potential (MMP) were detected by flow cytometry, and the protein expression of caspase-3 was observed by western blot. After exposure to OGD, the cell viability of cells treated with 0.01, 0.03, 0.10, 0.30, and 1.00 mg/mL of CSOL increased in a dose-effect relationship. Compared with the cells in the model group, the treatment of CSOL at all the experimental concentrations significantly inhibited both the cell apoptosis

  13. Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine

    PubMed Central

    Sham, Jonathan G.; Simianu, Vlad V.; Wright, Andrew S.; Stewart, Skye D.; Alloosh, Mouhamad; Sturek, Michael; Cummings, David E.; Flum, David R.

    2014-01-01

    Background. Roux-en-Y gastric bypass (RYGB) is the most common bariatric operation; however, the mechanism underlying the profound weight-independent effects on glucose homeostasis remains unclear. Large animal models of naturally occurring insulin resistance (IR), which have been lacking, would provide opportunities to elucidate such mechanisms. Ossabaw miniature swine naturally exhibit many features that may be useful in evaluating the anti diabetic effects of bariatric surgery. Methods. Glucose homeostasis was studied in 53 Ossabaw swine. Thirty-two received an obesogenic diet and were randomized to RYGB, gastrojejunostomy (GJ), gastrojejunostomy with duodenal exclusion (GJD), or Sham operations. Intravenous glucose tolerance tests and standardized meal tolerance tests were performed prior to, 1, 2, and 8 weeks after surgery and at a single time-point for regular diet control pigs. Results. High-calorie-fed Ossabaws weighed more and had greater IR than regular diet controls, though only 70% developed IR. All operations caused weight-loss-independent improvement in IR, though only in pigs with high baseline IR. Only RYGB induced weight loss and decreased IR in the majority of pigs, as well as increasing AUCinsulin/AUCglucose. Conclusions. Similar to humans, Ossabaw swine exhibit both obesity-dependent and obesity-independent IR. RYGB promoted weight loss, IR improvement, and increased AUCinsulin/AUCglucose, compared to the smaller changes following GJ and GJD, suggesting a combination of upper and lower gut mechanisms in improving glucose homeostasis. PMID:25215301

  14. Improved CEEMDAN and PSO-SVR Modeling for Near-Infrared Noninvasive Glucose Detection

    PubMed Central

    Li, Xiaoli

    2016-01-01

    Diabetes is a serious threat to human health. Thus, research on noninvasive blood glucose detection has become crucial locally and abroad. Near-infrared transmission spectroscopy has important applications in noninvasive glucose detection. Extracting useful information and selecting appropriate modeling methods can improve the robustness and accuracy of models for predicting blood glucose concentrations. Therefore, an improved signal reconstruction and calibration modeling method is proposed in this study. On the basis of improved complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and correlative coefficient, the sensitive intrinsic mode functions are selected to reconstruct spectroscopy signals for developing the calibration model using the support vector regression (SVR) method. The radial basis function kernel is selected for SVR, and three parameters, namely, insensitive loss coefficient ε, penalty parameter C, and width coefficient γ, are identified beforehand for the corresponding model. Particle swarm optimization (PSO) is employed to optimize the simultaneous selection of the three parameters. Results of the comparison experiments using PSO-SVR and partial least squares show that the proposed signal reconstitution method is feasible and can eliminate noise in spectroscopy signals. The prediction accuracy of model using PSO-SVR method is also found to be better than that of other methods for near-infrared noninvasive glucose detection. PMID:27635151

  15. Improved CEEMDAN and PSO-SVR Modeling for Near-Infrared Noninvasive Glucose Detection.

    PubMed

    Li, Xiaoli; Li, Chengwei

    2016-01-01

    Diabetes is a serious threat to human health. Thus, research on noninvasive blood glucose detection has become crucial locally and abroad. Near-infrared transmission spectroscopy has important applications in noninvasive glucose detection. Extracting useful information and selecting appropriate modeling methods can improve the robustness and accuracy of models for predicting blood glucose concentrations. Therefore, an improved signal reconstruction and calibration modeling method is proposed in this study. On the basis of improved complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and correlative coefficient, the sensitive intrinsic mode functions are selected to reconstruct spectroscopy signals for developing the calibration model using the support vector regression (SVR) method. The radial basis function kernel is selected for SVR, and three parameters, namely, insensitive loss coefficient ε, penalty parameter C, and width coefficient γ, are identified beforehand for the corresponding model. Particle swarm optimization (PSO) is employed to optimize the simultaneous selection of the three parameters. Results of the comparison experiments using PSO-SVR and partial least squares show that the proposed signal reconstitution method is feasible and can eliminate noise in spectroscopy signals. The prediction accuracy of model using PSO-SVR method is also found to be better than that of other methods for near-infrared noninvasive glucose detection.

  16. Cost implications to health care payers of improving glucose management among adults with type 2 diabetes.

    PubMed

    Nuckols, Teryl K; McGlynn, Elizabeth A; Adams, John; Lai, Julie; Go, Myong-Hyun; Keesey, Joan; Aledort, Julia E

    2011-08-01

    Objective. To assess the cost implications to payers of improving glucose management among adults with type 2 diabetes. Data Source/Study Setting. Medical-record data from the Community Quality Index (CQI) study (1996-2002), pharmaceutical claims from four Massachusetts health plans (2004-2006), Medicare Fee Schedule (2009), published literature. Study Design. Probability tree depicting glucose management over 1 year. Data Collection/Extraction Methods. We determined how frequently CQI study subjects received recommended care processes and attained Health Care Effectiveness Data and Information Set (HEDIS) treatment goals, estimated utilization of visits and medications associated with recommended care, assigned costs based on utilization, and then modeled how hospitalization rates, costs, and goal attainment would change if all recommended care was provided. Principal Findings. Relative to current care, improved glucose management would cost U.S.$327 (U.S.$192-711 in sensitivity analyses) more per person with diabetes annually, largely due to antihyperglycemic medications. Cost-effectiveness to payers, defined as incremental annual cost per patient newly attaining any one of three HEDIS goals, would be U.S.$1,128; including glycemic crises reduces this to U.S.$555-1,021. Conclusions. The cost of improving glucose management appears modest relative to diabetes-related health care expenditures. The incremental cost per patient newly attaining HEDIS goals enables payers to consider costs as well as outcomes that are linked to future profitability.

  17. Methylene Blue Protects Astrocytes against Glucose Oxygen Deprivation by Improving Cellular Respiration

    PubMed Central

    Roy Choudhury, Gourav; Winters, Ali; Rich, Ryan M.; Ryou, Myoung-Gwi; Gryczynski, Zygmunt; Yuan, Fang; Yang, Shao-Hua; Liu, Ran

    2015-01-01

    Astrocytes outnumber neurons and serve many metabolic and trophic functions in the mammalian brain. Preserving astrocytes is critical for normal brain function as well as for protecting the brain against various insults. Our previous studies have indicated that methylene blue (MB) functions as an alternative electron carrier and enhances brain metabolism. In addition, MB has been shown to be protective against neurodegeneration and brain injury. In the current study, we investigated the protective role of MB in astrocytes. Cell viability assays showed that MB treatment significantly protected primary astrocytes from oxygen-glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the effect of MB on cellular oxygen and glucose metabolism in primary astrocytes following OGD-reoxygenation injury. MB treatment significantly increased cellular oxygen consumption, glucose uptake and ATP production in primary astrocytes. In conclusion our study demonstrated that MB protects astrocytes against OGD-reoxygenation injury by improving astrocyte cellular respiration. PMID:25848957

  18. Methylene blue protects astrocytes against glucose oxygen deprivation by improving cellular respiration.

    PubMed

    Roy Choudhury, Gourav; Winters, Ali; Rich, Ryan M; Ryou, Myoung-Gwi; Gryczynski, Zygmunt; Yuan, Fang; Yang, Shao-Hua; Liu, Ran

    2015-01-01

    Astrocytes outnumber neurons and serve many metabolic and trophic functions in the mammalian brain. Preserving astrocytes is critical for normal brain function as well as for protecting the brain against various insults. Our previous studies have indicated that methylene blue (MB) functions as an alternative electron carrier and enhances brain metabolism. In addition, MB has been shown to be protective against neurodegeneration and brain injury. In the current study, we investigated the protective role of MB in astrocytes. Cell viability assays showed that MB treatment significantly protected primary astrocytes from oxygen-glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the effect of MB on cellular oxygen and glucose metabolism in primary astrocytes following OGD-reoxygenation injury. MB treatment significantly increased cellular oxygen consumption, glucose uptake and ATP production in primary astrocytes. In conclusion our study demonstrated that MB protects astrocytes against OGD-reoxygenation injury by improving astrocyte cellular respiration.

  19. Improving Oral Communication Skills of Students in Food Science Courses

    ERIC Educational Resources Information Center

    Reitmeier, C. A.; Svendsen, L. K.; Vrchota, D. A.

    2004-01-01

    Communication activities about food evaluation were incorporated into food preparation courses. Oral reports replaced quizzes and an oral presentation replaced the final exam. A rubric was developed to help students evaluate ingredient functions, procedures, techniques, temperatures, and sensory evaluation. Oral report scores, self-evaluations,…

  20. Improving Oral Communication Skills of Students in Food Science Courses

    ERIC Educational Resources Information Center

    Reitmeier, C. A.; Svendsen, L. K.; Vrchota, D. A.

    2004-01-01

    Communication activities about food evaluation were incorporated into food preparation courses. Oral reports replaced quizzes and an oral presentation replaced the final exam. A rubric was developed to help students evaluate ingredient functions, procedures, techniques, temperatures, and sensory evaluation. Oral report scores, self-evaluations,…

  1. Zinc finger protein 407 overexpression upregulates PPAR target gene expression and improves glucose homeostasis in mice.

    PubMed

    Charrier, Alyssa; Wang, Li; Stephenson, Erin J; Ghanta, Siddharth V; Ko, Chih-Wei; Croniger, Colleen M; Bridges, Dave; Buchner, David A

    2016-11-01

    The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors is central to the pathophysiology and treatment of metabolic disease through the receptors' ability to regulate the expression of genes involved in glucose homeostasis, adipogenesis, and lipid metabolism. However, the mechanism by which PPAR is regulated remains incompletely understood. We generated a transgenic mouse strain (ZFP-TG) that overexpressed Zfp407 primarily in muscle and heart. Transcriptome analysis by RNA-Seq identified 1,300 differentially expressed genes in the muscle of ZFP-TG mice, among which PPAR target genes were significantly enriched. Among the physiologically important PPARγ target genes, Glucose transporter (Glut)-4 mRNA and protein levels were increased in heart and muscle. The increase in Glut4 and other transcriptional effects of Zfp407 overexpression together decreased body weight and lowered plasma glucose, insulin, and HOMA-IR scores relative to control littermates. When placed on high-fat diet, ZFP-TG mice remained more glucose tolerant than their wild-type counterparts. Cell-based assays demonstrated that Zfp407 synergistically increased the transcriptional activity of all PPAR subtypes, PPARα, PPARγ, and PPARδ. The increased PPAR activity was not associated with increased PPAR mRNA or protein levels, suggesting that Zfp407 posttranslationally regulates PPAR activity. Collectively, these results demonstrate that Zfp407 overexpression improved glucose homeostasis. Thus, Zfp407 represents a new drug target for treating metabolic disease. Copyright © 2016 the American Physiological Society.

  2. Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119.

    PubMed

    Park, Eun-Young; Kim, Eung-Hwi; Kim, Chul-Young; Kim, Mi-Hwi; Choung, Jin-Seung; Oh, Yoon-Sin; Moon, Hong-Sub; Jun, Hee-Sook

    2016-01-01

    G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes.

  3. Accuracy of Subcutaneous Continuous Glucose Monitoring in Critically Ill Adults: Improved Sensor Performance with Enhanced Calibrations

    PubMed Central

    Leelarathna, Lalantha; English, Shane W.; Thabit, Hood; Caldwell, Karen; Allen, Janet M.; Kumareswaran, Kavita; Wilinska, Malgorzata E.; Nodale, Marianna; Haidar, Ahmad; Evans, Mark L.; Burnstein, Rowan

    2014-01-01

    Abstract Objective: Accurate real-time continuous glucose measurements may improve glucose control in the critical care unit. We evaluated the accuracy of the FreeStyle® Navigator® (Abbott Diabetes Care, Alameda, CA) subcutaneous continuous glucose monitoring (CGM) device in critically ill adults using two methods of calibration. Subjects and Methods: In a randomized trial, paired CGM and reference glucose (hourly arterial blood glucose [ABG]) were collected over a 48-h period from 24 adults with critical illness (mean±SD age, 60±14 years; mean±SD body mass index, 29.6±9.3 kg/m2; mean±SD Acute Physiology and Chronic Health Evaluation score, 12±4 [range, 6–19]) and hyperglycemia. In 12 subjects, the CGM device was calibrated at variable intervals of 1–6 h using ABG. In the other 12 subjects, the sensor was calibrated according to the manufacturer's instructions (1, 2, 10, and 24 h) using arterial blood and the built-in point-of-care glucometer. Results: In total, 1,060 CGM–ABG pairs were analyzed over the glucose range from 4.3 to 18.8 mmol/L. Using enhanced calibration median (interquartile range) every 169 (122–213) min, the absolute relative deviation was lower (7.0% [3.5, 13.0] vs. 12.8% [6.3, 21.8], P<0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%). Conclusions: Accuracy of the Navigator CGM device during critical illness was comparable to that observed in non–critical care settings. Further significant improvements in accuracy may be obtained by frequent calibrations with ABG measurements. PMID:24180327

  4. Angiotensin 1-7 improves insulin sensitivity by increasing skeletal muscle glucose uptake in vivo.

    PubMed

    Echeverría-Rodríguez, Omar; Del Valle-Mondragón, Leonardo; Hong, Enrique

    2014-01-01

    The renin-angiotensin system (RAS) regulates skeletal muscle insulin sensitivity through different mechanisms. The overactivation of the ACE (angiotensin-converting enzyme)/Ang (angiotensin) II/AT1R (Ang II type 1 receptor) axis has been associated with the development of insulin resistance, whereas the stimulation of the ACE2/Ang 1-7/MasR (Mas receptor) axis improves insulin sensitivity. The in vivo mechanisms by which this axis enhances skeletal muscle insulin sensitivity are scarcely known. In this work, we investigated whether rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis and determined the effect of Ang 1-7 on rat skeletal muscle glucose uptake in vivo. Western blot analysis revealed the expression of ACE2 and MasR, while Ang 1-7 levels were detected in rat soleus muscle by capillary zone electrophoresis. The euglycemic clamp exhibited that Ang 1-7 by itself did not promote glucose transport, but it increased insulin-stimulated glucose disposal in the rat. In a similar manner, captopril (an ACE inhibitor) enhanced insulin-induced glucose uptake and this effect was blocked by the MasR antagonist A-779. Our results show for the first time that rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis of the RAS, and Ang 1-7 improves insulin sensitivity by enhancing insulin-stimulated glucose uptake in rat skeletal muscle in vivo. Thus, endogenous (systemic and/or local) Ang 1-7 could regulate insulin-mediated glucose transport in vivo.

  5. Hemolysis is a major cause of variability in insulin measurement during oral glucose tolerance test in children.

    PubMed

    Bellomo, Giorgio; Sulas, Maria Giovanna; Mairate, Elisabetta; Bardone, Maria Beatrice; Rolla, Roberta

    2012-01-01

    The oral glucose tolerance test (OGTT) is widely employed to evaluate insulin resistance in children with growth hormone deficiency. Due to the difficulty in blood sampling, hemolysis is a frequent pre-analytic interference. The present study was performed to characterize the effects of hemolysis on insulin assays, in order to assess the need to generate automatic hemolysis reports and/or to reject hemolyzed samples. Insulin plasma levels were measured using a Siemens ADVIA Centaur on samples obtained from children with suspected GH deficiency at risk for insulin resistance during OGTT. The presence of hemolysis (with a concentration of free hemoglobin above 75 mg/dL) promotes a dose- and time-dependent decrease in immunoreactive insulin at any time-point evaluated during OGTT. As a consequence, the variability of insulin is particularly high (often exceeding 100% of the mean value) as compared to that of glucose. This variability is markedly reduced after removal of the hemolyzed samples. When hemolysis is not taken into account a misinterpretation of insulin secretion pattern can occur. It is therefore imperative to: (i) analyze blood samples immediately after sampling, (ii) reject samples with a concentration of free hemoglobin equal to or above 125 mg/dL and (iii) always report the possible interference.

  6. The effect of treatment on pregnancy outcomes in women with one elevated oral glucose tolerance test value.

    PubMed

    Kokanalı, Mahmut Kuntay; Tokmak, Aytekin; Kaymak, Oktay; Cavkaytar, Sabri; Bilge, Ümit

    2014-10-01

    The aim of the study was to evaluate whether dietary intervention could reduce maternal and perinatal morbidity in pregnancies with one elevated 100 g oral glucose tolerance test (OGTT) value. The study was conducted among patients with positive 50 g glucose challenge test (GCT) and one elevated 100 g OGTT value. Plasma glucose value of 140 mg/dL was used as the threshold to define an abnormal GCT result. Carpenter and Coustan criteria were used to evaluate the OGTT results. Seventy-four women with normal GCT values comprised group I. Ninety-nine women with one elevated 100 g OGTT value who were given a caloric diet and 102 women with one elevated OGTT value in group III who received antenatal care with no special diet were randomly assigned to groups II and III, respectively. All women were followed up until the end of pregnancy. Poor maternal outcome was defined as: cesarean delivery performed due to cephalopelvic disproportion, failure to progress or fetal distress, preeclampsia, and/or preterm labor. Poor perinatal outcome was defined as: small for gestational age, large for gestational age or admission to a neonatal intensive care unit. The groups were compared in terms of maternal and perinatal outcomes. The rates of macrosomia and large for gestational age incidence were significantly higher in group III as compared to groups I and II. When we examined the multivariate effects of the risk factors considered to be predictive of poor maternal outcomes, group III was the only statistically significant risk factor (OR=3.90, 95% CI:1.95- 7.84; p=<0.001). In terms of poor perinatal outcome, one elevated OGTT value (group III) was the only significant risk factor (OR=2.92, 95% CI:1.56-5.46; p=<0.001). Women with one elevated OGTT value benefit from a structured program of diet therapy aimed to reduce adverse maternal and perinatal outcomes.

  7. Clinical outcomes of pregnancies complicated by mild gestational diabetes mellitus differ by combinations of abnormal oral glucose tolerance test values.

    PubMed

    Black, Mary Helen; Sacks, David A; Xiang, Anny H; Lawrence, Jean M

    2010-12-01

    To examine the association between levels of hyperglycemia, determined by each prenatal oral glucose tolerance test (OGTT) value (fasting, 1 and 2 h), and maternal and perinatal outcomes and to determine whether the risk for these outcomes differs for women whose value(s) equaled or exceeded the thresholds for gestational diabetes mellitus (GDM) established by the International Association of Diabetes in Pregnancy Study Groups (IADPSG). This article discusses a retrospective study of 8,711 women, delivering at ≥ 20 weeks' gestation, who had a prenatal 2-h 75-g OGTT without a prior 50-g challenge and were not treated with insulin, glyburide, diet, and/or exercise during pregnancy. Associations between adverse outcomes and elevated OGTT values are reported. After excluding treated women, 19.4% of the remaining women had IADPSG-defined GDM. Continuous fasting, 1- and 2-h OGTT measures, and GDM (yes/no) were significantly associated with most adverse outcomes. However, the magnitude and significance of risk for these outcomes differed by various combinations of abnormal glucose values. Women with normal fasting and elevated postload values were at higher risk for preterm delivery, gestational hypertension, and having an infant with hyperbilirubinema, whereas women with elevated fasting and normal postload values were at higher risk of having a large-for-gestational-age infant, compared with women without GDM. Risks for different adverse outcomes vary depending on which single or combined IADPSG-defined OGTT thresholds are equaled or exceeded. Prospective studies are needed to determine whether changing pre- and postprandial glucose targets during pregnancy will more uniformly reduce adverse outcomes.

  8. Clinical Outcomes of Pregnancies Complicated by Mild Gestational Diabetes Mellitus Differ by Combinations of Abnormal Oral Glucose Tolerance Test Values

    PubMed Central

    Black, Mary Helen; Sacks, David A.; Xiang, Anny H.; Lawrence, Jean M.

    2010-01-01

    OBJECTIVE To examine the association between levels of hyperglycemia, determined by each prenatal oral glucose tolerance test (OGTT) value (fasting, 1 and 2 h), and maternal and perinatal outcomes and to determine whether the risk for these outcomes differs for women whose value(s) equaled or exceeded the thresholds for gestational diabetes mellitus (GDM) established by the International Association of Diabetes in Pregnancy Study Groups (IADPSG). RESEARCH DESIGN AND METHODS This article discusses a retrospective study of 8,711 women, delivering at ≥20 weeks' gestation, who had a prenatal 2-h 75-g OGTT without a prior 50-g challenge and were not treated with insulin, glyburide, diet, and/or exercise during pregnancy. Associations between adverse outcomes and elevated OGTT values are reported. RESULTS After excluding treated women, 19.4% of the remaining women had IADPSG-defined GDM. Continuous fasting, 1- and 2-h OGTT measures, and GDM (yes/no) were significantly associated with most adverse outcomes. However, the magnitude and significance of risk for these outcomes differed by various combinations of abnormal glucose values. Women with normal fasting and elevated postload values were at higher risk for preterm delivery, gestational hypertension, and having an infant with hyperbilirubinema, whereas women with elevated fasting and normal postload values were at higher risk of having a large-for-gestational-age infant, compared with women without GDM. CONCLUSIONS Risks for different adverse outcomes vary depending on which single or combined IADPSG-defined OGTT thresholds are equaled or exceeded. Prospective studies are needed to determine whether changing pre- and postprandial glucose targets during pregnancy will more uniformly reduce adverse outcomes. PMID:20843973

  9. Oral zinc supplementation may improve cognitive function in schoolchildren.

    PubMed

    de Moura, José Edson; de Moura, Edna Nubia Oliveira; Alves, Camila Xavier; Vale, Sancha Helena de Lima; Dantas, Márcia Marília Gomes; Silva, Alfredo de Araújo; Almeida, Maria das Graças; Leite, Lúcia Dantas; Brandão-Neto, José

    2013-10-01

    Zinc is an important micronutrient for humans, and zinc deficiency among schoolchildren is deleterious to growth and development, immune competence, and cognitive function. However, the effect of zinc supplementation on cognitive function remains poorly understood. The purpose of our study was to evaluate the effect of oral zinc supplementation (5 mg Zn/day for 3 months) on the Full Scale Intelligence Quotient (FSIQ), Verbal Intelligence Quotient (VIQ), and Performance Intelligence Quotient (PIQ) using a Wechsler Intelligence Scale for Children (WISC-III). We studied 36 schoolchildren aged 6 to 9 years (7.8 ± 1.1) using a nonprobability sampling method. The baseline serum zinc concentrations increased significantly after zinc supplementation (p < 0.0001), with no difference between sexes. Tests were administered under basal conditions before and after zinc supplementation, and there was no difference in FSIQ according to gender or age. The results demonstrated that zinc improved the VIQ only in the Information Subtest (p = 0.009), although the supplementation effects were more significant in relation to the PIQ, as these scores improved for the Picture Completion, Picture Arrangement, Block Design, and Object Assembly Subtests (p = 0.0001, for all subtests). In conclusion, zinc supplementation improved specific cognitive abilities, thereby positively influencing the academic performance of schoolchildren, even those without marginal zinc deficiency.

  10. Improving oral health in women: nurses' call to action.

    PubMed

    Clemmens, Donna A; Kerr, A Ross

    2008-01-01

    The purpose of this article is to discuss the most significant oral health and related problems experienced by women, and to provide a Nurse's Plan of Action to respond to these largely preventable diseases. Oral health is integral to women's overall health and well-being, with poor oral health being associated with cancer, heart disease, diabetes, depression, and the birth of preterm, low-birthweight babies. Poor nutrition and lifestyle, principally tobacco and heavy alcohol use, can further increase the risk for oral diseases. Disparities are evident in women's reported poor access of regular dental care related to lack of dental insurance and low income. These facts are disturbing because most oral diseases are preventable. The Surgeon General's report on oral health in America (U.S. Department of Health and Human Services, 2000) and, more recently, the "National Call to Action to Promote Oral Health" (U.S. Department of Health and Human Services, 2003) emphasized the need for partnerships of key stakeholders, including nurses, to get involved in oral disease prevention. Nurses are in an ideal position to provide health promotion education and screening across the multitude of settings in which they work regarding oral health and risk factors for oral disease. Nursing interventions aimed at promoting healthy outcomes and preventing disease should include a focus on oral health.

  11. Incretin effect and glucagon responses to oral and intravenous glucose in patients with maturity-onset diabetes of the young--type 2 and type 3.

    PubMed

    Østoft, Signe H; Bagger, Jonatan I; Hansen, Torben; Pedersen, Oluf; Holst, Jens J; Knop, Filip K; Vilsbøll, Tina

    2014-08-01

    Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of nonautoimmune diabetes, constituting 1-2% of all diabetes. Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and intravenous glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), respectively, and in matched healthy control subjects. Both MODY groups exhibited glucose intolerance after oral glucose (most pronounced in patients with HNF1A-diabetes), but only patients with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon responses to OGTT. Both groups of patients with diabetes showed normal suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes, similar to type 2 diabetes, is characterized by an impaired incretin effect and inappropriate glucagon responses, whereas incretin effect and glucagon response to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differences between the two MODY forms. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Potentiation of insulin secretion and improvement of glucose intolerance by combining a novel G protein-coupled receptor 40 agonist DS-1558 with glucagon-like peptide-1 receptor agonists.

    PubMed

    Nakashima, Ryutaro; Yano, Tatsuya; Ogawa, Junko; Tanaka, Naomi; Toda, Narihiro; Yoshida, Masao; Takano, Rieko; Inoue, Masahiro; Honda, Takeshi; Kume, Shoen; Matsumoto, Koji

    2014-08-15

    G protein-coupled receptor 40 (GPR40) is a Gq-coupled receptor for free fatty acids predominantly expressed in pancreatic β-cells. In recent years, GPR40 agonists have been investigated for use as novel therapeutic agents in the treatment of type 2 diabetes. We discovered a novel small molecule GPR40 agonist, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid (DS-1558). The GPR40-mediated effects of DS-1558 on glucose-stimulated insulin secretion were evaluated in isolated islets from GPR40 knock-out and wild-type (littermate) mice. The GPR40-mediated effects on glucose tolerance and insulin secretion were also confirmed by an oral glucose tolerance test in these mice. Furthermore, oral administration of DS-1558 (0.03, 0.1 and 0.3mg/kg) significantly and dose-dependently improved hyperglycemia and increased insulin secretion during the oral glucose tolerance test in Zucker fatty rats, the model of insulin resistance and glucose intolerance. Next, we examined the combination effects of DS-1558 with glucagon like peptide-1 (GLP-1). DS-1558 not only increased the glucose-stimulated insulin secretion by GLP-1 but also potentiated the maximum insulinogenic effects of GLP-1 after an intravenous glucose injection in normal Sprague Dawley rats. Furthermore, the glucose lowering effects of exendin-4, a GLP-1 receptor agonist, were markedly potentiated by the DS-1558 (3mg/kg) add-on in diabetic db/db mice during an intraperitoneal glucose tolerance test. In conclusion, our results indicate that add-on GPR40 agonists to GLP-1 related agents might be a potential treatment compared to single administration of these compounds. Therefore the combinations of these agents are a novel therapeutic option for type 2 diabetes.

  13. Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion.

    PubMed

    Salunkhe, Vishal A; Mollet, Inês G; Ofori, Jones K; Malm, Helena A; Esguerra, Jonathan L S; Reinbothe, Thomas M; Stenkula, Karin G; Wendt, Anna; Eliasson, Lena; Vikman, Jenny

    2016-08-01

    Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca(2+) signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Acute low-dose endotoxin treatment results in improved whole-body glucose homeostasis in mice.

    PubMed

    Stevens, Joseph R; McMillan, Ryan P; Resendes, Justin T; Lloyd, Shannon K; Ali, Mostafa M; Frisard, Madlyn I; Hargett, Stefan; Keller, Susanna R; Hulver, Matthew W

    2017-03-01

    Obese individuals present with an increased inflammatory tone as compared to healthy, normal-weight individuals, which is associated with insulin resistance. One factor hypothesized to contribute to increased inflammation in obese and diabetic states is elevated blood endotoxin levels, a condition known as metabolic endotoxemia. In non-obese and insulin sensitive individuals, circulating endotoxin concentrations fluctuate over the course of the day with elevations in the post-prandial state that return to baseline levels in the post-absorptive state. Evidence suggests that high-fat feeding alters these fluctuations causing endotoxin levels to remain high throughout the day. The effects of alterations in endotoxin levels on glucose metabolism are not clearly understood. The goal of this study was to determine the effects of both short-term and long-term increases in endotoxin (lipopolysaccharide, LPS) of a low magnitude on the glucose tolerance and insulin signaling in a human primary cell line as well as the effects of short-term endotoxin treatments on glucose homeostasis in a C57/Bl6 mouse model. First, we tested the hypothesis that short-term low-dose endotoxin treatments would augment insulin signaling and glycogen synthesis while long-term treatments would be disruptive in the cell culture model. Second, we examined if these short-term low dose treatments of endotoxin would contribute to similar improvements in whole-body glucose homeostasis in a mouse model. Contrary to our initial hypothesis, short-term endotoxin treatment had no effect on insulin signaling or glycogen synthesis, however long-term treatment indeed decreased glycogen synthesis (P<.05). Interestingly, short-term endotoxin treatment resulted in significant improvements in glucose homeostasis in the mouse model (P<.01); which is believed to be at least partly attributed to an inhibitory action of LPS on liver glucose production. This research shows that low-magnitude, short-term changes in LPS

  15. Identification of the mechanism of action of a glucokinase activator from oral glucose tolerance test data in type 2 diabetic patients based on an integrated glucose-insulin model.

    PubMed

    Jauslin, Petra M; Karlsson, Mats O; Frey, Nicolas

    2012-12-01

    A mechanistic drug-disease model was developed on the basis of a previously published integrated glucose-insulin model by Jauslin et al. A glucokinase activator was used as a test compound to evaluate the model's ability to identify a drug's mechanism of action and estimate its effects on glucose and insulin profiles following oral glucose tolerance tests. A kinetic-pharmacodynamic approach was chosen to describe the drug's pharmacodynamic effects in a dose-response-time model. Four possible mechanisms of action of antidiabetic drugs were evaluated, and the corresponding affected model parameters were identified: insulin secretion, glucose production, insulin effect on glucose elimination, and insulin-independent glucose elimination. Inclusion of drug effects in the model at these sites of action was first tested one-by-one and then in combination. The results demonstrate the ability of this model to identify the dual mechanism of action of a glucokinase activator and describe and predict its effects: Estimating a stimulating drug effect on insulin secretion and an inhibiting effect on glucose output resulted in a significantly better model fit than any other combination of effect sites. The model may be used for dose finding in early clinical drug development and for gaining more insight into a drug candidate's mechanism of action.

  16. Reduction of Fasting Blood Glucose and Hemoglobin A1c Using Oral Aloe Vera: A Meta-Analysis.

    PubMed

    Dick, William R; Fletcher, Emily A; Shah, Sachin A

    2016-06-01

    Diabetes mellitus is a global epidemic and one of the leading causes of morbidity and mortality. Additional medications that are novel, affordable, and efficacious are needed to treat this rampant disease. This meta-analysis was performed to ascertain the effectiveness of oral aloe vera consumption on the reduction of fasting blood glucose (FBG) and hemoglobin A1c (HbA1c). PubMed, CINAHL, Natural Medicines Comprehensive Database, and Natural Standard databases were searched. Studies of aloe vera's effect on FBG, HbA1c, homeostasis model assessment-estimated insulin resistance (HOMA-IR), fasting serum insulin, fructosamine, and oral glucose tolerance test (OGTT) in prediabetic and diabetic populations were examined. After data extraction, the parameters of FBG and HbA1c had appropriate data for meta-analyses. Extracted data were verified and then analyzed by StatsDirect Statistical Software. Reductions of FBG and HbA1c were reported as the weighted mean differences from baseline, calculated by a random-effects model with 95% confidence intervals. Subgroup analyses to determine clinical and statistical heterogeneity were also performed. Publication bias was assessed by using the Egger bias statistic. Nine studies were included in the FBG parameter (n = 283); 5 of these studies included HbA1c data (n = 89). Aloe vera decreased FBG by 46.6 mg/dL (p < 0.0001) and HbA1c by 1.05% (p = 0.004). Significant reductions of both endpoints were maintained in all subgroup analyses. Additionally, the data suggest that patients with an FBG ≥200 mg/dL may see a greater benefit. A mean FBG reduction of 109.9 mg/dL was observed in this population (p ≤ 0.0001). The Egger statistic showed publication bias with FBG but not with HbA1c (p = 0.010 and p = 0.602, respectively). These results support the use of oral aloe vera for significantly reducing FBG (46.6 mg/dL) and HbA1c (1.05%). Further clinical studies that are more robust and better

  17. Photoacoustic signals denoising of the glucose aqueous solutions using an improved wavelet threshold method

    NASA Astrophysics Data System (ADS)

    Ren, Zhong; Liu, Guodong; Xiong, Zhihua

    2016-10-01

    The photoacoustic signals denoising of glucose is one of most important steps in the quality identification of the fruit because the real-time photoacoustic singals of glucose are easily interfered by all kinds of noises. To remove the noises and some useless information, an improved wavelet threshld function were proposed. Compared with the traditional wavelet hard and soft threshold functions, the improved wavelet threshold function can overcome the pseudo-oscillation effect of the denoised photoacoustic signals due to the continuity of the improved wavelet threshold function, and the error between the denoised signals and the original signals can be decreased. To validate the feasibility of the improved wavelet threshold function denoising, the denoising simulation experiments based on MATLAB programmimg were performed. In the simulation experiments, the standard test signal was used, and three different denoising methods were used and compared with the improved wavelet threshold function. The signal-to-noise ratio (SNR) and the root-mean-square error (RMSE) values were used to evaluate the performance of the improved wavelet threshold function denoising. The experimental results demonstrate that the SNR value of the improved wavelet threshold function is largest and the RMSE value is lest, which fully verifies that the improved wavelet threshold function denoising is feasible. Finally, the improved wavelet threshold function denoising was used to remove the noises of the photoacoustic signals of the glucose solutions. The denoising effect is also very good. Therefore, the improved wavelet threshold function denoising proposed by this paper, has a potential value in the field of denoising for the photoacoustic singals.

  18. Improving the safety of oral immunotherapy for food allergy.

    PubMed

    Vazquez-Ortiz, Marta; Turner, Paul J

    2016-03-01

    Food allergy is a major public health problem in children, impacting upon the affected individual, their families and others charged with their care, for example educational establishments, and the food industry. In contrast to most other paediatric diseases, there is no established cure: current management is based upon dietary avoidance and the provision of rescue medication in the event of accidental reactions, which are common. This strategy has significant limitations and impacts adversely on health-related quality of life. In the last decade, research into disease-modifying treatments for food allergy has emerged, predominantly for peanut, egg and cow's milk. Most studies have used the oral route (oral immunotherapy, OIT), in which increasing amounts of allergen are given over weeks-months. OIT has proven effective to induce immune modulation and 'desensitization' - that is, an increase in the amount of food allergen that can be consumed, so long as regular (typically daily) doses are continued. However, its ability to induce permanent tolerance once ongoing exposure has stopped seems limited. Additionally, the short- and long-term safety of OIT is often poorly reported, raising concerns about its implementation in routine practice. Most patients experience allergic reactions and, although generally mild, severe reactions have occurred. Long-term adherence is unclear, which rises concerns given the low rates of long-term tolerance induction. Current research focuses on improving current limitations, especially safety. Strategies include alternative routes (sublingual, epicutaneous), modified hypoallergenic products and adjuvants (anti-IgE, pre-/probiotics). Biomarkers of safe/successful OIT are also under investigation.

  19. Ileal Interposition in Rats with Experimental Type 2 Like Diabetes Improves Glycemic Control Independently of Glucose Absorption

    PubMed Central

    Jurowich, Christian Ferdinand; Otto, Christoph; Wagner, Nicole; Vrhovac, Ivana; Sabolić, Ivan; Germer, Christoph-Thomas; Koepsell, Hermann

    2015-01-01

    Bariatric operations in obese patients with type 2 diabetes often improve diabetes before weight loss is observed. In patients mainly Roux-en-Y-gastric bypass with partial stomach resection is performed. Duodenojejunal bypass (DJB) and ileal interposition (IIP) are employed in animal experiments. Due to increased glucose exposition of L-cells located in distal ileum, all bariatric surgery procedures lead to higher secretion of antidiabetic glucagon like peptide-1 (GLP-1) after glucose gavage. After DJB also downregulation of Na+-d-glucose cotransporter SGLT1 was observed. This suggested a direct contribution of decreased glucose absorption to the antidiabetic effect of bariatric surgery. To investigate whether glucose absorption is also decreased after IIP, we induced diabetes with decreased glucose tolerance and insulin sensitivity in male rats and investigated effects of IIP on diabetes and SGLT1. After IIP, we observed weight-independent improvement of glucose tolerance, increased insulin sensitivity, and increased plasma GLP-1 after glucose gavage. The interposed ileum was increased in diameter and showed increased length of villi, hyperplasia of the epithelial layer, and increased number of L-cells. The amount of SGLT1-mediated glucose uptake in interposed ileum was increased 2-fold reaching the same level as in jejunum. Thus, improvement of glycemic control by bariatric surgery does not require decreased glucose absorption. PMID:26185767

  20. Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

    PubMed

    Hirata, Ayumu; Funato, Hiroki; Nakai, Megumi; Iizuka, Michiro; Abe, Noriaki; Yagi, Yusuke; Shiraishi, Hisashi; Jobu, Kohei; Yokota, Junko; Hirose, Kahori; Hyodo, Masamitsu; Miyamura, Mitsuhiko

    2016-01-01

    We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

  1. Higher incremental insulin area under the curve during oral glucose tolerance test predicts less food intake and weight gain.

    PubMed

    He, J; Votruba, S; Venti, C; Krakoff, J

    2011-12-01

    To investigate the correlation of peripheral insulin concentrations with food intake and body weight. Cross sectional and longitudinal clinical study: we investigated the association of peripheral insulin concentrations in response to an oral glucose tolerance test (OGTT) with subsequent measures of ad libitum food intake and body weight change. Food intake analysis: Pima Indians (n=67, 63% male; body mass index (mean ± s.d.) 34.2 ± 9.4 kg m(-2)) with normal glucose regulation (NGR; fasting glucose <5.6 mmol l(-1) and 2-h glucose <7.8 mmol l(-1)) participated in a study of ad libitum food intake measured over 3 days by an automated vending machine system. Weight change analysis: Pima Indians with NGR (n=339) who also participated in a longitudinal study of risks for type 2 diabetes and had follow-up weights. Food intake analysis: incremental area under the curve (iAUC) for insulin during the OGTT was negatively associated with mean daily ad libitum energy intake (DEI) (r=-0.26, P=0.04), calories consumed as percent weight-maintenance energy needs (%WMEN) (r=-0.38, P=0.002) and carbohydrate intake (gram per day) (r=-0.35, P=0.005). Adjustment for age and sex attenuated the association of iAUC with DEI (P=0.06) not with %WMEN and carbohydrate intake (P=0.005, P=0.008). Weight change analysis: after adjustment for age, sex, follow-up time and initial body weight, higher insulin iAUC predicted less absolute and percent weight change (β=-6.9, P=0.02; β=-0.08, P=0.008, respectively). In healthy Pima Indians with NGR, higher plasma iAUC during an OGTT predicted lower food intake and carbohydrate consumption and less weight gain. These data indicated a role for peripheral insulin as a negative feedback signal in the regulation of energy intake and body weight.

  2. Reduction of hepatic insulin clearance after oral glucose ingestion is not mediated by glucagon-like peptide 1 or gastric inhibitory polypeptide in humans.

    PubMed

    Meier, Juris J; Holst, Jens J; Schmidt, Wolfgang E; Nauck, Michael A

    2007-09-01

    Changes in hepatic insulin clearance can occur after oral glucose or meal ingestion. This has been attributed to the secretion and action of gastric inhibitory polypeptide (GIP) and glucagon-like peptide (GLP)-1. Given the recent availability of drugs based on incretin hormones, such clearance effects may be important for the future treatment of type 2 diabetes. Therefore, we determined insulin clearance in response to endogenously secreted and exogenously administered GIP and GLP-1. Insulin clearance was estimated from the molar C-peptide-to-insulin ratio calculated at basal conditions and from the respective areas under the curve after glucose, GIP, or GLP-1 administration. Oral glucose administration led to an approximately 60% reduction in the C-peptide-to-insulin ratio (P < 0.0001), whereas intravenous glucose administration had no effect (P = 0.09). The endogenous secretion of GIP or GLP-1 was unrelated to the changes in insulin clearance. The C-peptide-to-insulin ratio was unchanged after the intravenous administration of GIP or GLP-1 in the fasting state (P = 0.27 and P = 0.35, respectively). Likewise, infusing GLP-1 during a meal course did not alter insulin clearance (P = 0.87). An inverse nonlinear relationship was found between the C-peptide-to-insulin ratio and the integrated insulin levels after oral and during intravenous glucose administration. Insulin clearance is reduced by oral but not by intravenous glucose administration. Neither GIP nor GLP-1 has significant effects on insulin extraction. An inverse relationship between insulin concentrations and insulin clearance suggests that the secretion of insulin itself determines the rate of hepatic insulin clearance.

  3. Exaggerated glucagon-like peptide 1 response is important for improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes.

    PubMed

    Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N; Jacobsen, Siv H; Worm, Dorte; Hansen, Dorte L; Kristiansen, Viggo B; Naver, Lars; Madsbad, Sten; Holst, Jens J

    2013-09-01

    β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)-specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

  4. Exercise training is an effective alternative to estrogen supplementation for improving glucose homeostasis in ovariectomized rats

    PubMed Central

    MacDonald, Tara L; Ritchie, Kerry L; Davies, Sarah; Hamilton, Melissa J; Cervone, Daniel T; Dyck, David J

    2015-01-01

    The irreversible loss of estrogen (specifically 17-β-estradiol; E2) compromises whole-body glucose tolerance in women. Hormone replacement therapy (HRT) is frequently prescribed to treat estrogen deficiency, but has several deleterious side effects. Exercise has been proposed as an HRT substitute, however, their relative abilities to treat glucose intolerance are unknown. Thirty ovariectomized (OVX) and 20 SHAM (control) rats underwent glucose tolerance tests (GTT) 10 weeks post surgery. Area under the curve (AUC) for OVX rats was 60% greater than SHAM controls (P = 0.0005). Rats were then randomly assigned to the following treatment groups: SHAM sedentary (sed) or exercise (ex; 60 min, 5×/weeks), OVX sed, ex, or E2 (28 μg/kg bw/day) for 4 weeks. OVX ex rats experienced a ∼45% improvement in AUC relative to OVX sed rats, whereas OVX E2 underwent a partial reduction (17%; P = 0.08). Maximal insulin-stimulated glucose uptake in soleus and EDL was not impaired in OVX rats, or augmented with exercise or E2. Akt phosphorylation did not differ in soleus, EDL, or liver of any group. However, OVX ex and OVX E2 experienced greater increases in p-Akt Ser473 in VAT and SQ tissues compared with SHAM and OVX sed groups. Mitochondrial markers CS, COXIV, and core1 were increased in soleus posttraining in OVX ex rats. The content of COXIV was reduced by 52% and 61% in SQ of OVX sed and E2 rats, compared to SHAM controls, but fully restored in OVX ex rats. In summary, exercise restores glucose tolerance in OVX rats more effectively than E2. This is not reflected by alterations in muscle maximal insulin response, but increased insulin signaling in adipose depots may underlie whole-body improvements. PMID:26603453

  5. Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults.

    PubMed

    Pollack, Rena M; Barzilai, Nir; Anghel, Valentin; Kulkarni, Ameya S; Golden, Aaron; O'Broin, Pilib; Sinclair, David A; Bonkowski, Michael S; Coleville, Alexander J; Powell, Danielle; Kim, Sharon; Moaddel, Ruin; Stein, Daniel; Zhang, Kehao; Hawkins, Meredith; Crandall, Jill P

    2017-03-16

    Resveratrol, a plant-derived polyphenol, has been reported to improve glucose metabolism and vascular function and to extend life span in animal models, but studies in humans have been inconclusive. In a randomized, double-blind crossover study, we treated older glucose-intolerant adults (n = 30) with resveratrol (2-3 g/daily) or placebo, each for 6 weeks. A standard mixed-meal test was used to assess insulin sensitivity (Matsuda index) and secretion (C-peptide deconvolution) and vascular function by reactive hyperemia peripheral arterial tonometry. Skeletal muscle samples were obtained for gene expression using RNA-Seq analysis and to assess mitochondrial morphology. There were no changes in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipid profile following resveratrol treatment. Fasting reactive hyperemia index improved with resveratrol (2.02 ± 0.2 vs 1.76 ± 0.02, p = .002). RNA-Seq analysis yielded 140 differentially expressed transcripts (corrected p-value ≤ .05), predominantly associated with mitochondrial genes and noncoding RNA. Ingenuity Pathway Analysis confirmed that mitochondrial dysfunction (p = 2.77 × 10-12) and oxidative phosphorylation (p = 1.41 × 10-11) were the most significantly perturbed pathways. Mitochondrial number, but not size, was increased. Resveratrol treatment of older adults with impaired glucose regulation may have beneficial effects on vascular function, but not glucose metabolism or insulin sensitivity. Changes in gene expression suggest effects similar to those observed with caloric restriction, which has been shown to increase life and health span in animal models, although its significance for humans is uncertain. Future human studies should address the appropriate dose range and low bioavailability of resveratrol.

  6. Isolated duodenal exclusion increases energy expenditure and improves glucose homeostasis in diet-induced obese rats

    PubMed Central

    Muñoz, Rodrigo; Carmody, Jill S.; Stylopoulos, Nicholas; Davis, Philip

    2012-01-01

    Roux-en-Y gastric bypass (RYGB) in rodent models reduces food intake (FI), increases resting energy expenditure (EE), and improves glycemic control. We have shown that mimicking the duodenal component of RYGB by implantation of a 10-cm endoluminal sleeve device (ELS-10) induces weight loss and improves glycemic control in diet-induced obese (DIO) rats. We sought to determine the mechanisms and structural requirements of these effects. We examined the effects of ELS-10 devices implanted in male DIO rats on body weight, food intake (FI), meal patterns, total and resting EE, and multiple parameters of glucose homeostasis, comparing them with sham-operated (SO) rats and with SO rats weight matched to the ELS-10-treated group. To determine the extent of duodenal exclusion required to influence metabolic outcomes, we compared the effects of implanting 10-, 4-, or 1-cm ELS devices. ELS-10 rats exhibited 13% higher total and 9% higher resting EE than SO controls. ELS-10 rats also exhibited enhanced postprandial GLP-1 secretion and improved glucose tolerance and insulin sensitivity out of proportion to the effects of weight loss alone. Implantation of 4- or 1-cm ELS devices had no effect on EE and limited effects on glucose homeostasis. Complete duodenal exclusion with ELS-10 induces weight loss by decreasing FI and increasing EE and improves glycemic control through weight loss-independent mechanisms. Thus signals originating in the proximal small intestine appear to exert a direct influence on the physiological regulation of EE and glucose homeostasis. Their selective manipulation could provide effective new therapies for obesity and diabetes that mimic the benefits of RYGB. PMID:22972837

  7. The interleukin-1 receptor antagonist anakinra improves first-phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance.

    PubMed

    van Poppel, P C M; van Asseldonk, E J P; Holst, J J; Vilsbøll, T; Netea, M G; Tack, C J

    2014-12-01

    Inflammation at the level of the β cell appears to be involved in progressive β-cell dysfunction in type 2 diabetes. We assessed the effect of blocking interleukin-1 (IL-1) by anakinra [recombinant human interleukin-1 receptor antagonist (IL-1Ra)] on β-cell function. Sixteen participants with impaired glucose tolerance were treated with 150 mg anakinra daily for 4 weeks in a double blind, randomized, placebo-controlled cross-over study with a wash-out period of 4 weeks. At the end of each treatment period, oral glucose tolerance tests (OGTTs) and hyperglycaemic clamps were performed. First-phase insulin secretion improved after anakinra treatment compared with placebo, 148 ± 20 versus 123 ± 14 mU/l, respectively (p = 0.03), and the insulinogenic index was higher after anakinra treatment. These results support the concept of involvement of IL-1β in the (progressive) decrease of insulin secretion capacity associated with type 2 diabetes.

  8. Leptin Rapidly Improves Glucose Homeostasis in Obese Mice by Increasing Hypothalamic Insulin Sensitivity

    PubMed Central

    Koch, Christiane; Augustine, Rachael A.; Steger, Juliane; Ganjam, Goutham K.; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W.; Shepherd, Peter R.; Anderson, Greg M.; Grattan, David R.; Tups, Alexander

    2013-01-01

    Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lepob/ob mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes. PMID:21123564

  9. Using skin impedance to improve prediction accuracy of continuous glucose monitoring system

    NASA Astrophysics Data System (ADS)

    Yu, Haixia; Liu, Jin; Shi, Ting; Li, Dachao; Du, Zhenhui; Xu, Kexin

    2008-02-01

    The continuous blood glucose monitoring system using interstitial fluid (ISF) extracted by ultrasound and vacuum is proposed in this paper. The skin impedance measurement is introduced into the system to monitor the skin permeability variation. Low-frequency ultrasound is applied on skin surface to enhance the skin permeability by disrupting the lipid bilayers of the stratum corneum (SC), and then ISF is extracted out of skin continuously by vacuum. The extracted ISF is diluted and the concentration of glucose in it is detected by a biosensor and used to predict the blood glucose concentration. The skin permeability is variable during the extraction, and its variation affects the prediction accuracy. The skin impedance is an excellent indicator of skin permeability in that the lipid bilayers of the SC, which offer electrical resistance to the skin, retard transdermal transport of molecules. So the skin impedance measured during the extraction is transformed to skin conductivity to estimate correlation coefficient between skin conductivity and permeability. Skin conductivity correlates well with skin permeability. The method and experiment system mentioned above may be significative for improving the prediction accuracy of continuous blood glucose monitoring system.

  10. Improved Properties of Baker's Yeast Mutants Resistant to 2-Deoxy-d-Glucose

    PubMed Central

    Rincón, Ana M.; Codón, Antonio C.; Castrejón, Francisco; Benítez, Tahía

    2001-01-01

    We isolated spontaneous mutants from Saccharomyces cerevisiae (baker's yeast V1) that were resistant to 2-deoxy-d-glucose and had improved fermentative capacity on sweet doughs. Three mutants could grow at the same rate as the wild type in minimal SD medium (0.17% Difco yeast nitrogen base without amino acids and ammonium sulfate, 0.5% ammonium sulfate, 2% glucose) and had stable elevated levels of maltase and/or invertase under repression conditions but lower levels in maltose-supplemented media. Two of the mutants also had high levels of phosphatase active on 2-deoxy-d-glucose-6-phosphate. Dough fermentation (CO2 liberation) by two of the mutants was faster and/or produced higher final volumes than that by the wild type, both under laboratory and industrial conditions, when the doughs were supplemented with glucose or sucrose. However, the three mutants were slower when fermenting plain doughs. Fermented sweet bakery products obtained with these mutants were of better quality than those produced by the wild type, with regard to their texture and their organoleptic properties. PMID:11526034

  11. Improvement of embryonic stem cell line derivation efficiency with novel medium, glucose concentration, and epigenetic modifications.

    PubMed

    Kim, Chul; Amano, Tomokazu; Park, Joonghoon; Carter, Mark G; Tian, Xiuchun; Yang, Xiangzhong

    2009-03-01

    Although the first mouse embryonic stem (ES) cell lines were derived 2 decades ago, and standard protocols for ES cell derivation are widely used today, the technical difficulty of these protocols still pose a challenge for many investigators attempting to produce large numbers of ES cell lines, and are limited to only a few mouse strains. Recently, glucose concentration was shown to have a significant effect on the efficiency of ES cell derivation, but the mechanism(s) mediating this effect are still the subject of debate. In this report, we investigated the effect of glucose concentration on ES cell derivation efficiency from blastocysts in the context of a new medium, Minimum Essential Medium alpha (MEMalpha). Furthermore, we propose novel methods to improve mouse ES cell derivation efficiency using in vitro epigenetic modifications during early passages, combined with detection of Oct4-expressing cells. Based on the results reported here, modified MEMalpha containing high glucose improves the efficiency of ES cell derivation remarkably, compared with Knockout Dulbecco's-Modified Eagle Media (KDMEM). Epigenetic modifications are able to improve the efficiency even further.

  12. Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats

    PubMed Central

    Niu, Ho-Shan; Liu, I-Min; Niu, Chiang-Shan; Ku, Po-Ming; Hsu, Chao-Tien; Cheng, Juei-Tang

    2016-01-01

    Background Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin), is an herb used for renal dysfunction in Chinese traditional medicine. In an attempt to develop this herb as a treatment for diabetic nephropathy (DN), we investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic rats. Methods Streptozotocin (STZ) was used to induce type 1-like diabetes in rats (STZ-diabetic rats). In addition to hyperglycemia, STZ-diabetic rats showed significant nephropathy, including higher plasma levels of blood urea nitrogen, creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue was applied to characterize the changes in potential signals related to nephropathy. Results Oral administration of Du-Zhong (1 g/kg/day) to STZ-diabetic rats for 20 days not only decreased the plasma levels of blood urea nitrogen and creatinine but also improved renal fibrosis, whereas the plasma glucose level was not changed. The higher expressions of protein levels of transforming growth factor-beta (TGF-β) and connective tissue growth factor in diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong cannot reverse the hyperglycemia-induced overproduction of signal transducers and activators of transcription 3 in the diabetic kidney. Conclusion Oral administration of Du-Zhong improves STZ-induced DN in rats by inhibiting TGF-β/Smad signaling and suppressing TGF-β/connective tissue growth factor expression. Therefore, active principle from Du-Zhong is suitable to develop as new agent for DN in the future. PMID:27041999

  13. The sweet taste of success: the presence of glucose in the oral cavity moderates the depletion of self-control resources.

    PubMed

    Hagger, Martin S; Chatzisarantis, Nikos L D

    2013-01-01

    According to the resource-depletion model, self-control is a limited resource that is depleted after a period of exertion. Evidence consistent with this model indicates that self-control relies on glucose metabolism and glucose supplementation to depleted individuals replenishes self-control resources. In five experiments, we tested an alternative hypothesis that glucose in the oral cavity counteracts the deleterious effects of self-control depletion. We predicted a glucose mouth rinse, as opposed to an artificially sweetened placebo rinse, would lead to better self-control after depletion. In Studies 1 to 3, participants engaging in a depleting task performed significantly better on a subsequent self-control task after receiving a glucose mouth rinse, as opposed to participants rinsing with a placebo. Studies 4 and 5 replicated these findings and demonstrated that the glucose mouth rinse had no effect on self-control in nondepleted participants. Results are consistent with a neural rather than metabolic mechanism for the effect of glucose supplementation on self-control.

  14. The effect of kind of carbohydrate in the diet and use of oral contraceptives on metabolism of young women. III. Serum glucose, insulin, and glucagon.

    PubMed

    Behall, K M; Moser, P B; Kelsay, J L; Prather, E S

    1980-05-01

    Responses of glucose, insulin, and glucagon in serum to a sucrose load dose of young women taking oral contraceptives (OC) were compared to responses to the load dose of women who had never taken OC. Two experimental diets contained about 13% of the calories from protein, 36% from fat, and 51% from carbohydrate. Of the carbohydrate 84% was either sucrose of wheat starch. The diets were fed in a crossover design. Subjects were fed a sucrose load (1 g/kg) before and after weeks 1 and 3 of each dietary period. Parameters were measured in blood drawn before and 30, 60, 120, and 180 min after the meal. Levels of serum glucagon and responses of serum glucose and insulin to sucrose load were significantly higher in OC users than in controls. Glucose and insulin rose significantly after the sucrose load. Time significantly affected glucose and insulin. The OC-time interaction also was significant for glucose and insulin levels. The OC users generally had higher peak levels of glucose and insulin and took longer to return to fasting levels than did the controls. After 3 weeks on the diet, the glucose and insulin responses of the OC users, but not of the controls, were significantly greater on the sucrose than on the starch diet. The response of the insulin/glucagon ratio to the sucrose load was not significantly affected by the OC use.

  15. Simulation on how to customize glucose adjustment method for non-invasive blood glucose sensing by NIRS

    NASA Astrophysics Data System (ADS)

    Min, Xiaolin; Jiang, Jingying; Zou, Da; Liu, Rong; Xu, Kexin

    2013-02-01

    Previous studies have shown the limitations of taking OGTT (Oral Glucose Tolerance Test) as the glucose adjustment protocol for non-invasive blood glucose sensing. Previous studies built a mathematical model of glucose metabolism system-IMM (the Integrated Minimal Model) to probe other available adjustment methods. In this talk, a further study would be focused on more detailed combination options of different glucose input types for glucose adjustment projects in non-invasive blood glucose sensing. And predictive models of blood glucose concentration have been established by means of partial least squares (PLS) method, which could be used to evaluate the quality of different glucose adjustment options. Results of PLS modeling suggested that predictive models under combined glucose input types, compared with OGTT, show a great enhancement in the stability. This would finally improve the precision of non-invasive blood glucose sensing.

  16. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease.

    PubMed

    Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne

    2010-01-01

    Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.

  17. Improving Students with Rubric-Based Self-Assessment and Oral Feedback

    ERIC Educational Resources Information Center

    Barney, S.; Khurum, M.; Petersen, K.; Unterkalmsteiner, M.; Jabangwe, R.

    2012-01-01

    Rubrics and oral feedback are approaches to help students improve performance and meet learning outcomes. However, their effect on the actual improvement achieved is inconclusive. This paper evaluates the effect of rubrics and oral feedback on student learning outcomes. An experiment was conducted in a software engineering course on requirements…

  18. Evaluation of Student Reflection as a Route to Improve Oral Communication

    ERIC Educational Resources Information Center

    Mineart, Kenneth P.; Cooper, Matthew E.

    2016-01-01

    This study describes the use of guided self-reflection and peer feedback activities to improve student oral communication in a large ChE class (n ~ 100) setting. Student performance tracked throughout an experimental semester indicated both reflection activities accelerated improvement in oral communication over control; student perception of the…

  19. Improving Students with Rubric-Based Self-Assessment and Oral Feedback

    ERIC Educational Resources Information Center

    Barney, S.; Khurum, M.; Petersen, K.; Unterkalmsteiner, M.; Jabangwe, R.

    2012-01-01

    Rubrics and oral feedback are approaches to help students improve performance and meet learning outcomes. However, their effect on the actual improvement achieved is inconclusive. This paper evaluates the effect of rubrics and oral feedback on student learning outcomes. An experiment was conducted in a software engineering course on requirements…

  20. Evaluation of Student Reflection as a Route to Improve Oral Communication

    ERIC Educational Resources Information Center

    Mineart, Kenneth P.; Cooper, Matthew E.

    2016-01-01

    This study describes the use of guided self-reflection and peer feedback activities to improve student oral communication in a large ChE class (n ~ 100) setting. Student performance tracked throughout an experimental semester indicated both reflection activities accelerated improvement in oral communication over control; student perception of the…

  1. Improving the oral health of frail and functionally dependent elderly.

    PubMed

    Lewis, A; Wallace, J; Deutsch, A; King, P

    2015-03-01

    The Australian Government endorsed a national evidence based oral health model when it introduced the first Nursing Home Oral and Dental Health Plan in 2010. Called Better Oral Health in Residential Care, it promotes a multidisciplinary approach with doctors, nurses, care workers and dental professionals sharing responsibility for the four key processes of oral health screening, oral health care planning, daily oral hygiene and access to dental treatment. Frail and dependent residents are most conveniently treated on-site, hence an aged care/dental partnership is encouraged to facilitate the use of portable dental equipment in the delivery of dental care. Currently, few dentists provide services to residential aged care facilities (RACFs), with loss of clinical time in practice, difficulty in providing clinical care in a non-dental environment and lack of referral pathways from the RACFs to the dentists contributing to the problem. The need to establish a model of care involving dental hygienists/oral health therapists in RACFs has merit. Minimal intervention treatment using glass ionomer cement (GIC) and silver fluoride is ideal in aged care. However, GIC has limitation in dry mouths with low pH caused by polypharmacy or disease. Palliative and definitive treatment techniques need to be individualized with consideration of a patient's ability to maintain their own mouths as well as their mental and physical competence. The range of products available to address the oral diseases common to the frail elderly is growing. The oral health care provider is required to establish a preventive regime that is tailored to the patient's needs, is realistic and under revision as the patient's needs change. © 2015 Australian Dental Association.

  2. Endothelin A-receptor blockade in experimental diabetes improves glucose balance and gastrointestinal function.

    PubMed

    Balsiger, Bruno; Rickenbacher, Andreas; Boden, Penelope Jane; Biecker, Erwin; Tsui, Janice; Dashwood, Michael; Reichen, Jürg; Shaw, Sidney George

    2002-08-01

    Secondary complications of diabetes mellitus often involve gastrointestinal dysfunction. In the experimental Goto Kakizaki rat, a model of Type II diabetes, hyperglycaemia and reduced glucose clearance is associated with elevated plasma endothelin (ET)-1 levels and selective decreases in nitric oxide synthase in circular muscle, longitudinal muscle and neuronal elements of the gastrointestinal tract. Functionally, this is accompanied by decreased nitrergic relaxatory responses of jejunal longitudinal muscle to tetrodotoxin-sensitive electrical field stimulation. Long-term treatment with a selective ET A-type receptor antagonist, markedly reduced hyperglycaemia and restored plasma glucose clearance rates towards normal. This was associated with a restoration of N(G)-nitro-L-arginine methyl ester-sensitive relaxatory responses of jejunal longitudinal muscle to electrical field stimulation. The results indicate that beneficial effects of ETA receptor blockade on gastrointestinal function may result from an improvement in insulin sensitivity with concomitant reduction of the severity of hyperglycaemia. ETA receptor blockade may represent a new therapeutic principle for improving glucose tolerance in Type II diabetes and could be beneficial in alleviating or preventing hyperglycaemia-related secondary complications in this condition.

  3. Exogenous administration of spermine improves glucose utilization and decreases bodyweight in mice.

    PubMed

    Sadasivan, Satish Kumar; Vasamsetti, Balamuralikrishna; Singh, Jaideep; Marikunte, Venkataranganna V; Oommen, Anup Mammen; Jagannath, M R; Pralhada Rao, Raghavendra

    2014-04-15

    Polyamines are highly charged low molecular weight aliphatic polycations and are ubiquitously present in all living cells. In addition to their previously reported role in cell proliferation and cancer, recent studies support their role in energy homeostasis and glucose metabolism. In the present study we have evaluated a polyamine-spermine for its effect on glycemic, lipid and body weight parameters. High fat diet induced obese mice (6 week old male C57B6/J mice fed on high fat diet for 22 weeks) were dosed with spermine intraperitoneally at two different doses (5mg/kg and 10mg/kg body weight) for 4 weeks and its effect on body weight, glycemic and lipid parameters was monitored. We found that at a dose of 10mg/kg bodyweight, spermine treatment resulted in a 24% reduction in the body weight and 18% reduction in the fasting glucose compared to untreated controls. Besides, spermine treated mice exhibited improved glucose utilization associated with improved fat oxidation and loss of white adipose mass. Our study is promising in the direction of exploring the spermine and their analogs for treatment of metabolic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    PubMed

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  5. Gastrointestinal Microbiome Modulator Improves Glucose Tolerance in Overweight and Obese Subjects: A Randomized Controlled Pilot Trial

    PubMed Central

    Rebello, Candida J.; Burton, Jeffrey; Heiman, Mark; Greenway, Frank L.

    2015-01-01

    Objective The objective of this study was to examine the effects of a gastrointestinal microbiome modulator (GIMM) containing inulin, β-glucan, blueberry anthocyanins, and blueberry polyphenols on metabolic parameters, fecal markers of gut microbiota, and satiety. Design and Methods Thirty overweight or obese individuals aged 18 to 70 years, were enrolled in a randomized controlled trial. Participants consumed the test product or placebo daily for four weeks. Stool samples were collected and blood was drawn at baseline and week four for assessments of gut microbiota, satiety hormones, glucose control, and lipid measures. Subjective satiety was assessed weekly. Linear models were used to compare differences from baseline to week four. Results GIMM consumption improved blood glucose tolerance (p = 0.008), and increased satiety (p = 0.03). There were no statistically significant differences in insulin sensitivity, fecal markers of gut microbiota, plasma satiety hormones, or serum lipid concentrations between the groups. However, plasma satiety hormones and fecal short chain fatty acid concentrations increased in the test group compared to the placebo. Conclusions GIMM consumption for four weeks, increases satiety, and improves glucose tolerance possibly through insulin-independent pathways. PMID:26424589

  6. Improvement of hydrogen production from glucose by ferrous iron and biochar.

    PubMed

    Zhang, Jishi; Fan, Chuanfang; Zang, Lihua

    2017-09-01

    Effects of biochar (BC) and ferrous iron (Fe(2+)) additions on hydrogen (H2) production from glucose were investigated using batch experiment. The glucose with both BC and Fe(2+) additions were incubated at 37°C for H2 production. As compared with the control group (without BC and Fe(2+) additions), the synergic effects of BC and Fe(2+) make the lag phase time decease from 4.25 to 2.12h, and H2 yield increase from 158.0 to 234.4ml/g glucose. Moreover, suitable concentrations of BC and Fe(2+) serve to enhance volatile fatty acid generation during H2 evolution. These results indicate that H2 production is improved by BC and Fe(2+) regulations, where synergic mechanisms are described as follows: BC acts as support carriers of anaerobes and system pH buffers, which promotes the biofilm formation and maintains suitable pH environment; Appropriate Fe(2+) concentration can improve hydrogenase activity in H2 production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Opioid blockade effect on insulin beta-cells secretory patterns in polycystic ovary syndrome. Oral glucose load versus intravenous glucagon bolus.

    PubMed

    Ciampelli, M; Fulghesu, A M; Guido, M; Murgia, F; Muzj, G; Belosi, C; Fortini, A; Cento, R; Lanzone, A

    1998-01-01

    In order to evaluate the involvement of endogenous opiates in the insulin disorders of polycystic ovary syndrome (PCOs) a total of 25 PCOs women and 11 normo-ovulatory controls were studied by comparing the effect of a chronic opioid blockade on beta-cells responsiveness to oral glucose load and to intravenous glucagon bolus. Each patient, studied on follicular phase, underwent to oral glucose tolerance test (OGTT), and, 2 days later, to a glucagon intravenous bolus (1 mg); these tests were then repeated after 6 weeks of naltrexone treatment (50 mg orally). Naltrexone treatment did not modify the insulin secretory patterns of control subjects, whereas the same therapy significantly reduced, in hyperinsulinemic PCOs women, the beta-cell hyperresponsiveness both to oral glucose load and to intravenous glucagon (p < 0.05 and p < 0.01, respectively), even if with different mean percent decrease (32% OGTT vs. 45% glucagon, p < 0.05). Moreover, normoinsulinemic PCOs patients showed a slight, but not significantly increase in the beta-cells response to OGTT after opioid blockade, whereas, in the same situation, the insulin release after glucagon bolus was significantly reduced (p < 0.01). Chronic opioid blockade did not modify gonadotropins, steroids and SHBG levels in either group. Our data show that naltrexone treatment is able to reduce the beta-cell response to a direct intravenous secretagogue stimulus in all PCOs patients, while only in hyperinsulinemic PCOs subjects the same treatment is effective in reducing the exaggerated insulin secretion after oral glucose load. The reason for such a discrepancy could be ascribed to a different effect of opioids on first- and second-phase insulin secretion, or, alternatively, to an involvement of other secretagogue factors, such as glucoincretins.

  8. Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes.

    PubMed

    Khalili, Azadeh; Nekooeian, Ali Akbar; Khosravi, Mohammad Bagher

    2017-10-01

    Oleuropein mediates most of the beneficial effects of olive products. This study examined the role of oxidative stress in the effects of oleuropein on lipid profile and blood glucose in rats with simultaneous renovascular hypertension and type 2 diabetes. Eight groups (n = 7-9 each) of male Sprague-Dawley rats including a control, a type 2 diabetic, a renovascular hypertensive, a sham, a simultaneously hypertensive diabetic receiving vehicle, and 3 simultaneously hypertensive-diabetic receiving 20, 40, or 60 mg/kg/day oleuropein were used. Four weeks after treatment, blood glucose, lipid profile, and biomarkers of oxidative stress were measured, and glucose tolerance test (GTT) was performed. Simultaneously hypertensive diabetic rats had significantly higher blood pressure, blood glucose, and serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride and malondialdehyde. They also had lower serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and impaired glucose tolerance. Oleuropein significantly reduced blood pressure, blood glucose, and serum total cholesterol, LDL-C, triglyceride and malondoaldehyde. It also increased serum high-density lipoprotein cholesterol, erythrocyte superoxide dismutase, and improved glucose tolerance. The findings show that the model is associated with impaired glucose tolerance, and adverse lipid profile. They also show that oleuropein, partly by an antioxidant mechanism, improves glucose tolerance and changed lipid profile favorably.

  9. Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats.

    PubMed

    Ptilovanciv, Ellen On; Fernandes, Gabryelle S; Teixeira, Luciana C; Reis, Luciana A; Pessoa, Edson A; Convento, Marcia B; Simões, Manuel J; Albertoni, Guilherme A; Schor, Nestor; Borges, Fernanda T

    2013-01-16

    One important concern in the treatment of diabetes is the maintenance of glycemic levels and the prevention of diabetic nephropathy. Inducible heme oxygenase 1 (HO-1) is a rate-limiting enzyme thought to have antioxidant and cytoprotective roles. The goal of the present study was to analyze the effect of HO-1 induction in chronically hyperglycemic rats. The hyperglycemic rats were divided into two groups: one group, called STZ, was given a single injection of streptozotocin; and the other group was given a single streptozotocin injection as well as daily injections of hemin, an HO-1 inducer, over 60 days (STZ + HEME). A group of normoglycemic, untreated rats was used as the control (CTL).Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS) were assessed. After 60 days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. In the STZ + HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group.There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. In the STZ + HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. In conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant activity of HO-1.

  10. Genome shuffling enhanced ε-poly-L-lysine production by improving glucose tolerance of Streptomyces graminearus.

    PubMed

    Li, Shu; Li, Feng; Chen, Xu-S