title: Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect.
abstract: Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that stimulates insulin secretion and decreases glucagon release. It has been hypothesized that GLP-1 also reduces glycemia independent of its effect on islet hormones. Based on preliminary evidence that GLP-1 has independent actions on endogenous glucose production, we undertook a series of experiments that were optimized to address this question. The effect of GLP-1 on glucose appearance (Ra) and glucose disposal (Rd) was measured in eight men during a pancreatic clamp that was performed by infusing octreotide to suppress secretion of islet hormones, while insulin and glucagon were infused at rates adjusted to maintain blood glucose near fasting levels. After stabilization of plasma glucose and equilibration of [3H]glucose tracer, GLP-1 was given intravenously for 60 min. Concentrations of insulin, C-peptide, and glucagon were similar before and during the GLP-1 infusion (115 +/- 14 vs. 113 +/- 11 pM; 0.153 +/- 0.029 vs. 0.156 +/- 0.026 nM; and 64.7 +/- 11.5 vs. 65.8 +/- 13.8 ng/l, respectively). With the initiation of GLP-1, plasma glucose decreased in all eight subjects from steady-state levels of 4.8 +/- 0.2 to a nadir of 4.1 +/- 0.2 mM. This decrease in plasma glucose was accounted for by a significant 17% decrease in Ra, from 22.6 +/- 2.8 to 19.1 +/- 2.8 micromol. kg-1. min-1 (P < 0.04), with no significant change in Rd. These findings indicate that, under fasting conditions, GLP-1 decreases endogenous glucose production independent of its actions on islet hormone secretion.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Clinical Research Center, University of Washington, Baltimore, MD 21201, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Prigeon
authors.forename: Shaista
authors.initials: S
authors.lastname: Quddusi
authors.forename: Breay
authors.initials: B
authors.lastname: Paty
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D005934:Glucagon / Q000097:blood* / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015309:Glucose Clamp Technique / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood* / Q000494:pharmacology*; D011498:Protein Precursors / Q000097:blood* / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010187:Pancreatic Hormones; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose