Effects of glucagon‐like peptide 1 (7–36 amide) on whole‐body protein metabolism in healthy man

Abstract

The incretin glucagon‐like peptide 1 (GLP‐1) shows glucose‐dependent insulinotropic activity and may exert anabolic effects. Whole‐body protein metabolism was assessed by measuring [1‐¹³C]‐leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin‐mediated and direct GLP‐1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole‐body protein breakdown decreased markedly after 180 min of synthetic GLP‐1 infusion (GLP‐1 vs. placebo: P < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO₂ production during GLP‐1 administration (P < 0.0005). Plasma insulin increased after 3 h of GLP‐1 infusion to 1486 ± 145 pmol L⁻¹ vs. 185 ± 12 pmol L⁻¹ for saline (P < 0.0001). When plasma insulin levels were kept constant (GLP‐1 vs. saline, NS) during pancreatic clamping, GLP‐1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP‐1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP‐1‐induced stimulation of insulin secretion.