Beta Cell Function, Incretin Hormones and Incretin Effect in Obese Children and Adolescents with Prediabetes

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.

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Clinical characteristics and beta-cell function of Chinese children and adolescents with type 2 diabetes from 2009 to 2018

World Journal of Pediatrics ◽

10.1007/s12519-019-00243-5 ◽

2019 ◽

Vol 15 (4) ◽

pp. 405-411 ◽

Cited By ~ 3

Author(s):

Zhen-Ran Xu ◽

Miao-Ying Zhang ◽

Jin-Wen Ni ◽

Ruo-Qian Cheng ◽

Zhang-Qian Zheng ◽

...

Keyword(s):

Type 2 Diabetes ◽

Beta Cell ◽

Children And Adolescents ◽

Beta Cell Function ◽

Clinical Characteristics ◽

Cell Function ◽

Chinese Children ◽

Chinese Children And Adolescents

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Recovery of the Incretin Effect in Type 2 Diabetic Patients After Biliopancreatic Diversion

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-4042 ◽

2015 ◽

Vol 100 (5) ◽

pp. 1984-1988 ◽

Cited By ~ 8

Author(s):

Fernanda S. Novaes ◽

Ana C. J. Vasques ◽

José C. Pareja ◽

Filip K. Knop ◽

Andrea Tura ◽

...

Keyword(s):

Beta Cell ◽

Biliopancreatic Diversion ◽

Beta Cell Function ◽

Cell Function ◽

Diabetic Patients ◽

Obese Patients ◽

Incretin Effect ◽

Intravenous Glucose ◽

The Impact

Abstract Context: Bariatric surgery often results in remission of the diabetic state in obese patients. Increased incretin effect seems to play an important role in the glycemic improvements after Roux-en-Y gastric bypass, but the impact of biliopancreatic diversion (BPD) remains unexplored. Objective: The objective was to elucidate the effect of BPD on the incretin effect and its interplay with beta-cell function and insulin sensitivity (IS) in obese subjects with type 2 diabetes (T2DM). Design, Setting and Patients: Twenty-three women were studied: a control group of 13 lean, normal glucose-tolerant women (lean NGT) studied once and 10 obese patients with T2DM studied before, 1 and 12 months after BPD. Intervention: The ObeseT2DM group underwent BPD. Main Outcome Measures: The main outcome measure was the change in incretin effect as measured by the isoglycemic intravenous glucose infusion test. Secondary outcomes encompassed IS and beta-cell function. Results: At baseline, the incretin effect was lower in obese T2DM compared to lean NGT (P < .05). One month after BPD, the incretin effect was not changed, but at 12 months it reached the level of the lean NGT group (P > .05). IS improved (P < .05) 1 month after BPD and at 12 months it resembled the levels of the lean NGT group. Insulin secretory rate and beta-cell glucose sensitivity increased after BPD and achieved levels similar to lean NGT group 1 month after BPD and even higher levels at 12 months (P < .05). Conclusions: BPD has no acute impact on the reduced incretin effect, but 12 months after surgery the incretin effect normalizes alongside normalization of glucose control, IS and beta-cell function.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab151 ◽

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 <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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