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Diabetes Obes Metab. 2019 Nov 6. doi: 10.1111/dom.13906. [Epub ahead of print]

Role of endogenous glucagon-like peptide-1 enhanced by vildagliptin in the glycaemic and energy expenditure responses to intraduodenal fat infusion in type 2 diabetes.

Author information

1
Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia.
2
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.
3
Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
4
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Abstract

AIM:

To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin on glycaemic and energy expenditure responses during intraduodenal fat infusion, as well as the contribution of endogenous glucagon-like peptide-1 (GLP-1) signalling, in people with type 2 diabetes (T2DM).

METHODS:

A total of 15 people with T2DM managed by diet and/or metformin (glycated haemoglobin 49.3 ± 2.1 mmol/mol) were studied on three occasions (two with vildagliptin and one with placebo) in a double-blind, randomized, crossover fashion. On each day, vildagliptin 50 mg or placebo was given orally, followed by intravenous exendin (9-39) 600 pmol/kg/min, on one of the two vildagliptin treatment days, or 0.9% saline over 180 minutes. At between 0 and 120 minutes, a fat emulsion was infused intraduodenally at 2 kcal/min. Energy expenditure, plasma glucose and glucose-regulatory hormones were evaluated.

RESULTS:

Intraduodenal fat increased plasma GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and energy expenditure, and decreased plasma glucose (all P < 0.05). On the two intravenous saline days, plasma glucose and glucagon were lower, plasma intact GLP-1 was higher (all P < 0.05), and energy expenditure tended to be lower after vildagliptin (P = 0.08) than placebo. On the two vildagliptin days, plasma glucose, glucagon and GLP-1 (both total and intact), and energy expenditure were higher during intravenous exendin (9-39) than saline (all P < 0.05).

CONCLUSIONS:

In well-controlled T2DM during intraduodenal fat infusion, vildagliptin lowered plasma glucose and glucagon, and tended to decrease energy expenditure, effects that were mediated by endogenous GLP-1.

KEYWORDS:

DPP-4 inhibitor; GLP-1; energy regulation; glucagon; glycaemic control; type 2 diabetes

PMID:
31693275
DOI:
10.1111/dom.13906

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