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

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Abstract
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 µg/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.