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Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes
- Source :
- JCI insight. 3(23)
- Publication Year :
- 2017
-
Abstract
- BACKGROUND. Metformin reduces plasma glucose and has been shown to increase glucagon-like peptide 1 (GLP-1) secretion. Whether this is a direct action of metformin on GLP-1 release, and whether some of the glucose-lowering effect of metformin occurs due to GLP-1 release, is unknown. The current study investigated metformin-induced GLP-1 secretion and its contribution to the overall glucose-lowering effect of metformin and underlying mechanisms in patients with type 2 diabetes. METHODS. Twelve patients with type 2 diabetes were included in this placebo-controlled, double-blinded study. On 4 separate days, the patients received metformin (1,500 mg) or placebo suspended in a liquid meal, with subsequent i.v. infusion of the GLP-1 receptor antagonist exendin9-39 (Ex9-39) or saline. During 240 minutes, blood was sampled. The direct effect of metformin on GLP-1 secretion was tested ex vivo in human ileal and colonic tissue with and without dorsomorphin-induced inhibiting of the AMPK activity. RESULTS. Metformin increased postprandial GLP-1 secretion compared with placebo (P = 0.014), and the postprandial glucose excursions were significantly smaller after metformin + saline compared with metformin + Ex9-39 (P = 0.004). Ex vivo metformin acutely increased GLP-1 secretion (colonic tissue, P < 0.01; ileal tissue, P < 0.05), but the effect was abolished by inhibition of AMPK activity. CONCLUSIONS. Metformin has a direct and AMPK-dependent effect on GLP-1–secreting L cells and increases postprandial GLP-1 secretion, which seems to contribute to metformin’s glucose-lowering effect and mode of action. TRIAL REGISTRATION. {"type":"clinical-trial","attrs":{"text":"NCT02050074","term_id":"NCT02050074"}}NCT02050074 (https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02050074","term_id":"NCT02050074"}}NCT02050074). FUNDING. This study received grants from the A.P. Moller Foundation, the Novo Nordisk Foundation, the Danish Medical Association research grant, the Australian Research Council, the National Health and Medical Research Council, and Pfizer Inc.
- Subjects :
- 0301 basic medicine
Adult
Blood Glucose
Male
medicine.medical_specialty
endocrine system
endocrine system diseases
medicine.drug_class
030209 endocrinology & metabolism
Type 2 diabetes
Placebo
03 medical and health sciences
0302 clinical medicine
Double-Blind Method
Glucagon-Like Peptide 1
Internal medicine
Diabetes mellitus
medicine
Humans
Aged
Aged, 80 and over
business.industry
digestive, oral, and skin physiology
Australia
nutritional and metabolic diseases
General Medicine
Middle Aged
medicine.disease
Receptor antagonist
Postprandial Period
Glucagon-like peptide-1
Metformin
3. Good health
030104 developmental biology
Postprandial
Endocrinology
Diabetes Mellitus, Type 2
Female
business
Ex vivo
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Research Article
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 3
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- JCI insight
- Accession number :
- edsair.doi.dedup.....33f403c322c1f4f8b716675d01e1cc4c