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

Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic... 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 (R a ) and glucose disposal (R d ) 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 3 Hglucose 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 R a , from 22.6 ± 2.8 to 19.1 ± 2.8 µmol · kg – 1 · min – 1 ( P < 0.04), with no significant change in R d . These findings indicate that, under fasting conditions, GLP-1 decreases endogenous glucose production independent of its actions on islet hormone secretion. incretin; glucose production; pancreatic clamp; gastrointestinal hormone; glucose tolerance Address for reprint requests and other correspondence: D. D'Alessio, Univ. of Cincinnati, Division of Endocrinology, Box 670547, Cincinnati, OH 45267-0547 (E-mail: david.'alessio@uc.edu ). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Endocrinology and Metabolism The American Physiological Society

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

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References (50)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1849
eISSN
1522-1555
DOI
10.1152/ajpendo.00024.2003
pmid
12773303
Publisher site
See Article on Publisher Site

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 (R a ) and glucose disposal (R d ) 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 3 Hglucose 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 R a , from 22.6 ± 2.8 to 19.1 ± 2.8 µmol · kg – 1 · min – 1 ( P < 0.04), with no significant change in R d . These findings indicate that, under fasting conditions, GLP-1 decreases endogenous glucose production independent of its actions on islet hormone secretion. incretin; glucose production; pancreatic clamp; gastrointestinal hormone; glucose tolerance Address for reprint requests and other correspondence: D. D'Alessio, Univ. of Cincinnati, Division of Endocrinology, Box 670547, Cincinnati, OH 45267-0547 (E-mail: david.'alessio@uc.edu ).

Journal

AJP - Endocrinology and MetabolismThe American Physiological Society

Published: Oct 1, 2003

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