Stromal Derived Factor 1 alpha (SDF-1a) in a Dual Therapy with the DPP-4 Inhibitor 1 Vildagliptin does not Enhance Beta Cell Function but Improves Glucose Clearance after Oral Glucose in Streptozotocin Diabetic Mice

2016 ◽  
Vol 01 (02) ◽  
Author(s):  
Omara B ◽  
Liehuaa L ◽  
Ahren B
Keyword(s):  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Dual Therapy ◽  
Oral Glucose ◽  
Diabetic Mice ◽  
Glucose Clearance

Nr4a1 and Nr4a3 Knock Out Mice Have Impaired Glucose Clearance and Beta-Cell Function under High-Fat Feeding

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2040-P
Author(s):  
COURTNEY J. SMITH ◽  
KYLE B. KENER ◽  
JEFFERY S. TESSEM
Keyword(s):  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
High Fat ◽  
Knock Out ◽  
Glucose Clearance ◽  
Knock Out Mice ◽  
Fat Feeding

scholarly journals Dipeptidyl-Peptidase-IV Inhibitors, Imigliptin and Alogliptin, Improve Beta-Cell Function in Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Xu Liu ◽  
Yang Liu ◽  
Hongzhong Liu ◽  
Haiyan Li ◽  
Jianhong Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Dipeptidyl Peptidase ◽  
Chinese Patients ◽  
Oral Glucose ◽  
Model Assessment

ObjectsImigliptin is a novel dipeptidyl peptidase-4 inhibitor. In the present study, we aimed to evaluate the effects of imigliptin and alogliptin on insulin resistance and beta-cell function in Chinese patients with type-2 diabetes mellitus (T2DM).MethodsA total of 37 Chinese T2DM patients were randomized to receive 25 mg imigliptin, 50 mg imigliptin, placebo, and 25 mg alogliptin (positive drug) for 13 days. Oral glucose tolerance tests were conducted at baseline and on day 13, followed by the oral minimal model (OMM).ResultsImigliptin or alogliptin treatment, compared with their baseline or placebo, was associated with higher beta-cell function parameters (φs and φtot) and lower glucose area under the curve (AUC) and postprandial glucose levels. The changes in the AUC for the glucose appearance rate between 0 and 120 min also showed a decrease in imigliptin or alogliptin groups. However, the insulin resistance parameter, fasting glucose, was not changed. For the homeostatic model assessment (HOMA-β and HOMA-IR) parameters or secretory units of islets in transplantation index (SUIT), no statistically significant changes were found both within treatments and between treatments.ConclusionsAfter 13 days of treatment, imigliptin and alogliptin could decrease glycemic levels by improving beta-cell function. By comparing OMM with HOMA or SUIT results, glucose stimulation might be more sensitive for detecting changes in beta-cell function.

scholarly journals Advancing Dinner Timing Is an Effective Strategy in Improving Glucose Tolerance in Free-Living Adults: A Randomized Cross-Over Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 585-585
Author(s):  
Hassan Dashti ◽  
Jesus Lopez ◽  
Céline Vetter ◽  
Millán Pérez-Ayala ◽  
Juan Carlos Baraza ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Disease Risk ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Effective Strategy ◽  
Free Living

Abstract Objectives Eating at times that conflict with our physiology and coincide with the biological evening has been associated with increased disease risk. In free-living adults from the ONTIME-MT study (#NCT03036592) study, we tested the hypothesis that advancing the timing of dinner relative to bedtime, simulated by advancing an evening oral glucose tolerance test (OGTT), will result in improved glucose control. Methods In a randomized, cross-over study design, following an 8h fast, each participant underwent two evening 2-hour 75-gram oral OGTT: early and late (4h vs. 1h prior to habitual bedtime), simulating early and late dinner timing. Habitual bedtime was determined using one-week of electronic sleep logs via smartphone application. The OGTT order was randomized and separated by 1-week washout period. Light intensity was kept bright (≥450 lux) and dim (0–25 lux) in the early and late conditions, respectively. Melatonin was assessed at the start and end of each OGTT by radioimmunoassay. Postprandial glucose and insulin were determined using incremental area under the curve (AUC). Insulin sensitivity and beta-cell function were evaluated using standard metrices: insulin sensitivity index (ISI), corrected insulin response (CIR), and disposition index (DI). Values were compared using paired t-tests and differences were considered significant at P < 0.05. Results A total of 750 participants (mean age = 37 ± 14; 70% female; mean BMI = 26.12 ± 5.66) underwent OGTTs in two evening timing conditions. As expected, melatonin levels were higher in the late vs. early condition (4.49 ± 4.15-fold lower in the early vs. late meal condition. In the early condition, there was an 8.68% lower AUC for glucose (P = .0001) and 4.4% higher insulin AUC (P = 0.059), relative to the late condition. In addition, the CIR was 16% (P = .0001) higher and the DI was higher by 20% (P = .014) in the early compared to the late condition. The ISI was similar in both conditions (P = 0.66). Conclusions In this large study, glucose tolerance was better during early vs. late evening OGTT. Better glucose tolerance was primarily attributed to improved insulin secretion and beta-cell function. These results indicate that for the general population, advancing dinner relative to bedtime may be a novel and an effective strategy to improve glucose tolerance. Funding Sources ONTIME-MT was funded by the NIH R01 grant R01DK105072.

scholarly journals HbA1c during early pregnancy reflects beta-cell dysfunction in women developing GDM

2020 ◽  
Vol 8 (2) ◽  
pp. e001751
Author(s):  
Latife Bozkurt ◽  
Christian S Göbl ◽  
Karoline Leitner ◽  
Giovanni Pacini ◽  
Alexandra Kautzky-Willer
Keyword(s):  
Beta Cell ◽  
Early Pregnancy ◽  
Beta Cell Function ◽  
Cell Function ◽  
Predictive Accuracy ◽  
High Specificity ◽  
Glucose Disposal ◽  
Large For Gestational Age ◽  
Oral Glucose ◽  
Altered Glucose

IntroductionIt is of current interest to assess eligibility of hemoglobin A1c (HbA1c) as a screening tool for earlier identification of women with risk for more severe hyperglycemia in pregnancy but data regarding accuracy are controversial. We aimed to evaluate if HbA1c mirrors pathophysiological precursors of glucose intolerance in early pregnancy that characterize women who develop gestational diabetes mellitus (GDM).Research design and methods220 pregnant women underwent an HbA1c measurement as well as an oral glucose tolerance test (OGTT) with multiple measurements of glucose, insulin and C-peptide for evaluation of insulin sensitivity and beta-cell function at 16th gestational week (IQR: 14–18). Clinical follow-ups were performed until end of pregnancy.ResultsIncreased maternal HbA1c ≥5.7% (39 mmol/mol) corresponding to pre-diabetes outside of pregnancy was associated with altered glucose dynamics during the OGTT. Pregnancies with early HbA1c ≥5.7% showed higher fasting (90.4±13.2 vs 79.7±7.2 mg/dL, p<0.001), mean (145.6±31.4 vs 116.2±21.4 mg/dL, p<0.001) as well as maximum glucose concentrations and tended to a delay in reaching the maximum glucose level compared with those with normal-range HbA1c (186.5±42.6 vs 147.8±30.1 mg/dL, p<0.001). Women with increased HbA1c showed impaired beta-cell function and differences in disposition index independent of body mass index status. We observed a high specificity for the HbA1c cut-off of 5.7% for GDM manifestation (0.96, 95% CI 0.91 to 0.98) or need of glucose-lowering medication (0.95, 95% CI 0.90 to 0.98) although overall predictive accuracy was moderate to fair. Further, elevated HbA1c was associated with higher risk for delivering large-for-gestational-age infants, also after adjustment for GDM status (OR 4.4, 95% CI 1.2 to 15.0, p=0.018).ConclusionsHbA1c measured before recommended routine screening period reflects early pathophysiological derangements in beta-cell function and glucose disposal that are characteristic of GDM development and may be useful in early risk stratification.

scholarly journals The Incretin Effect in Female Mice With Double Deletion of GLP-1 and GIP Receptors

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Bo Ahrén ◽  
Yuichiro Yamada ◽  
Yutaka Seino
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Insulin Response ◽  
Oral Glucose ◽  
Incretin Effect ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Female Mice

Abstract To establish the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) for the incretin effect after oral glucose, studies were undertaken in female mice with genetic deletion of receptors for GIP and GLP-1 (double incretin receptor knockout [DIRKO] mice) and their wild-type (WT) counterparts. Insulin secretion was explored after oral glucose (doses ranging from 0 to 100 mg), after intravenous glucose (doses ranging from 0 to 0.75 g/kg), and after oral and intravenous glucose at matching circulating glucose. DIRKO mice had glucose intolerance after oral glucose challenges in association with impaired beta-cell function. Suprabasal area under the curve for C-peptide (AUCC-peptide) correlated linearly with suprabasal AUCglucose both in WT (r = 0.942, P = .017) and DIRKO mice (r = 0.972, P = .006). The slope of this regression was lower in DIRKO than in WT mice (0.012 ± 0.006 vs 0.031 ± 0.006 nmol C-peptide/mmol glucose, P = .042). In contrast, there was no difference in the insulin response to intravenous glucose between WT and DIRKO mice. Furthermore, oral and intravenous glucose administration at matching glucose levels showed that the augmentation of insulin secretion after oral glucose (the incretin effect) in WT mice (11.8 ± 2.3 nmol/L min) was entirely absent in DIRKO mice (3.3 ± 1.2 nmol/L min). We conclude that GIP and GLP-1 are required for normal glucose tolerance and beta-cell function after oral glucose in mice, that they are the sole incretin hormones after oral glucose at higher dose levels, and that they contribute by 65% to insulin secretion after oral glucose.

scholarly journals The impact of low dose gliclazide on the incretin effect and indices of beta cell function

2021 ◽  
Author(s):  
Ruth L M Cordiner ◽  
Andrea Mari ◽  
Andrea Tura ◽  
Ewan R Pearson
Keyword(s):  
Beta Cell ◽  
Beta Cell Function ◽  
Low Dose ◽  
Cell Function ◽  
Late Phase ◽  
Oral Glucose ◽  
Incretin Effect ◽  
Lower Blood ◽  
Glucose Sensitivity ◽  
The Impact

Abstract Aims/Hypothesis Studies in permanent neonatal diabetes suggest that sulphonylureas lower blood glucose without causing hypoglycaemia, in part by augmenting the incretin effect. This mechanism has not previously been attributed to sulphonylureas in patients with type 2 diabetes (T2DM). We therefore aimed to evaluate the impact of low dose gliclazide on beta-cell function and incretin action in patients with T2DM. Methods Paired oral glucose tolerance tests and isoglycaemic infusions were performed to evaluate the difference in the classical incretin effect in the presence and absence of low dose gliclazide in 16 subjects with T2DM (HbA1c &lt;64mmol/mol, 8.0%) treated with diet or metformin monotherapy. Beta-cell function modelling was undertaken to describe the relationship between insulin secretion and glucose concentration. Results A single dose of 20mg gliclazide reduced mean glucose during the OGTT from 12.01 ± 0.56 to 10.82 ± 0.5 mmol/l (p=0.0006) (mean ± SEM). The classical incretin effect was augmented by 20mg gliclazide, from 35.5% (LQ 27.3, UQ 61.2) to 54.99% (34.8, 72.8) (p=0.049). Gliclazide increased beta-cell glucose sensitivity by 46% (Control 22.61 ± 3.94, Gliclazide 33.11 ± 7.83 (p=0.01)) as well as late-phase incretin potentiation (Control 0.92 ± 0.05, Gliclazide 1.285 ± 0.14 (p=0.038). Conclusions/Interpretation Low dose gliclazide reduces plasma glucose in response to oral glucose load, with concomitant augmentation of the classical incretin effect. Beta-cell modelling shows that low plasma concentrations of gliclazide potentiate late phase insulin secretion and increase glucose sensitivity by 50%. Further studies are merited to explore whether low dose gliclazide, by enhancing incretin action, could effectively lower blood glucose without risk of hypoglycaemia.

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