Effects of glucagon-like peptide 1 (7-36 amide) on whole-body protein metabolism in healthy man.
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 3h 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.
Shalev
A
A
Department of Medicine, University Hospital, Basle, Switzerland.
Holst
J J
JJ
Keller
U
U
D000328:Adult; D001786:Blood Glucose / Q000737:chemistry; D002096:C-Peptide / Q000097:blood; D002153:Calorimetry, Indirect; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007930:Leucine / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D010179:Pancreas / Q000502:physiology; D010446:Peptide Fragments; D010455:Peptides / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D007930:Leucine; D005990:Glycerol; C051322:glucagon-like peptide 1 (7-37)