GLP-1 does not not acutely affect insulin sensitivity in healthy man

• Published in: Diabetologia 1996-10, Vol.39 (10), p.1227-1232
• Main Authors: Orskov, L, Holst, J J, Møller, J, Orskov, C, Møller, N, Alberti, K G, Schmitz, O
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid; Adult; Alanine - blood; Analysis of Variance; Blood Glucose - drug effects; Blood Glucose - metabolism; C-Peptide - blood; C-Peptide - metabolism; Calorimetry, Indirect; Fatty Acids, Nonesterified - blood; Glucagon - blood; Glucagon - metabolism; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose Clamp Technique; Humans; Hydroxybutyrates - blood; Infusions, Intravenous; Insulin - blood; Insulin - metabolism; Insulin - pharmacology; Insulin Secretion; Lactates - blood; Male; Neurotransmitter Agents - pharmacology; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Reference Values; Somatostatin - administration & dosage; Somatostatin - pharmacology; Time Factors
• ISSN: 0012-186X

Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7-36 amide) may have the direct effect of increasing insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyper insulinaemic (0.8 mU.kg-1.min-1), euglycaemic (5 mmol/l) clamp. Somatostatin (450 micrograms/h was infused to suppress endogenous insulin secretion, and growth hormone (3 ng.kg-1.min-1) and glucagon (0.8 ng.kg-1.min-1) were infused to maintain basal levels. GLP-1 (50 pmol.kg-1.h-1) or 154 mmol/l NaCl (placebo) was infused after 3 h of equilibration, i.e. from 180-360 min. GLP-1 infusion resulted in GLP-1 levels of approximately 40 pmol/l. Plasma glucose, insulin, growth hormone, and glucagon levels were similar throughout the clamps. The rate of glucose infusion required to maintain euglycaemia was similar with or without GLP-1 infusion (7.69 +/- 1.17 vs 7.76 +/- 0.95 mg kg-1.min-1 at 150-180 min and 8.56 +/- 1.13 vs 8.55 +/- 0.68 mg.kg-1.min-1 at 330-360 min) and there was no difference in isotopically determined hepatic glucose production rates (-0.30 +/- 0.23 vs -0.16 +/- 0.22 mg.kg-1.min-1 at 330-360 min). Furthermore, arteriovenous glucose differences across the forearm were similar with or without GLP-1 infusion (1.43 +/- 0.23 vs 1.8 +/- 0.29 mmol/l), (ANOVA; p > 0.60, in all instances). In conclusion, GLP-1 (7-36 amide) administered for 3 h, leading to circulating levels within the physiological range, does not affect insulin sensitivity in healthy man.