Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes

• DOI: 10.1172/jci.insight.93936
• Publication Date: 2018-12-05T16:01:32Z
• Authors: Emilie Bahne; Emily W. L. Sun; Richard L. Young; Morten Hansen; David P. Sonne; Jakob S. Hansen; Ulrich Rohde; Alice P. Liou; Margaret L. Jackson; Dayan de Fontgalland; Philippa Rabbitt; Paul Hollington; Luigi Sposato; Steven Due; David A. Wattchow; Jens F. Rehfeld; Jens J. Holst; Damien J. Keating; Tina Vilsbøll; Filip K. Knop
• Keywords: Adult; Aged, 80 and over; Blood Glucose; Male; 0301 basic medicine; 0303 health sciences; 571; 4. Education; Diabetes; Australia; 610; Middle Aged; Postprandial Period; Metformin; 3. Good health; 03 medical and health sciences; Diabetes Mellitus, Type 2; Double-Blind Method; Glucagon-Like Peptide 1; Humans; Female; metabolism; Aged

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, whether some the glucose-lowering effect occurs due unknown. The current study investigated metformin-induced secretion its contribution overall underlying mechanisms in patients with type 2 diabetes.Twelve diabetes were included placebo-controlled, double-blinded study. On 4 separate days, received (1,500 mg) or placebo suspended liquid meal, subsequent i.v. infusion receptor antagonist exendin9-39 (Ex9-39) saline. During 240 minutes, blood was sampled. tested ex vivo human ileal colonic tissue without dorsomorphin-induced inhibiting AMPK activity.Metformin increased postprandial compared (P = 0.014), excursions significantly smaller after + saline Ex9-39 0.004). Ex acutely (colonic tissue, P < 0.01; 0.05), but abolished by inhibition AMPK-dependent GLP-1-secreting L cells increases secretion, which seems contribute metformin's mode action.NCT02050074 (https://clinicaltrials.gov/ct2/show/NCT02050074).This grants from A.P. Møller Foundation, Novo Nordisk Danish Medical Association research grant, Australian Research Council, National Health Pfizer Inc.