Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans.
The effect of glucagon-like peptide-1 (GLP-1) on hepatic glucose production and peripheral glucose utilization was investigated with or without infusion of somatostatin to inhibit insulin and glucagon secretion in 13 healthy, non-diabetic women aged 59 years. After 120 min 3-(3)H-glucose infusion, GLP-1 was added (4.5 pmol kg(-1) bolus + 1.5 pmol kg(-1) min(-1)). Without somatostatin (n = 6), GLP-1 decreased plasma glucose (from 4.8 +/- 0.2 to 4.2 +/- 0.3 mmol L(-1), P = 0.007). Insulin levels were increased (48 +/- 3 vs. 243 +/- 67 pmol L(-1), P = 0.032), as was the insulin to glucagon ratio (P = 0.044). The rate of glucose appearance (Ra) was decreased (P = 0.003) and the metabolic clearance rate of glucose (MCR) was increased during the GLP-1 infusion (P = 0.024 vs. saline). Also, the rate of glucose disappearance (Rd) was reduced during the GLP-1 infusion (P = 0.004). Since Ra was reduced more than Rd, the net glucose flow was negative, which reduced plasma glucose. Somatostatin infusion (500 microg h(-1), n = 7) abolished the effects of GLP-1 on plasma glucose, serum insulin, insulin to glucagon ratio, Ra, Rd, MCR and net glucose flow. The results suggest that GLP-1 reduces plasma glucose levels mainly by reducing hepatic glucose production and increasing the metabolic clearance rate of glucose through indirectly increasing the insulin to glucagon ratio in healthy subjects.
Larsson
H
H
Department of Medicine, Lund University, Malmö, Sweden.
Holst
J J
JJ
Ahrén
B
B
D001786:Blood Glucose / Q000378:metabolism; D003864:Depression, Chemical; D005260:Female; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000096:biosynthesis*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007329:Insulin Antagonists / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D006727:Hormone Antagonists; D007328:Insulin; D007329:Insulin Antagonists; D010455:Peptides; D013004:Somatostatin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose