Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect.

Autor: Prigeon, Ronald L., Quddusi, Shaista, Patty, Breay, D'Alessio, David A.
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Zdroj: American Journal of Physiology: Endocrinology & Metabolism; Oct2003, Vol. 48 Issue 4, pE701-E707, 7p, 1 Diagram, 2 Charts, 7 Graphs
Abstrakt: 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 m address this question. The effect of GLP-1 on glucose appearmace (R[sub a]) and glucose disposal (R[sub d]) was measured in eight men during a pancreatic clamp that was performed by infuslng 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 steadystate 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 R[sub a], from 22.6 ± 2.8 to 19.1 ± 2.8 µmol·kg[sup -1]·min[sup -1] (P < 0.04), with no significant change in R[sub d]. These findings indicate that, under fasting conditions, GLP-1 decreases endogenous glucose production independent of its actions on islet hormone secretion. [ABSTRACT FROM AUTHOR]
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