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

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 hyperinsulinaemic (0.8 mU . kg(-1). min(-1)), euglycaemic (5 mmol/l) clamp. Somatostatin (450 mu g/h) was infused to suppress endogenous insulin secretion, and growth hormone (3 ng . kg(-1). min(-1)) and glucagon (0.8 ngl . 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.