Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic β-cells (HIT)

Gordon C YANEY; Vildan N CIVELEK; Ann-Marie RICHARD; Joseph S DILLON; Jude T DEENEY; James A HAMILTON; Helen M KORCHAK; Keith TORNHEIM; Barbara E CORKEY; Aubrey E BOYD

doi:10.2337/diabetes.50.1.56

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Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic β-cells (HIT)

Journal article

Peer reviewed

Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic β-cells (HIT)

Gordon C YANEY, Vildan N CIVELEK, Ann-Marie RICHARD, Joseph S DILLON, Jude T DEENEY, James A HAMILTON, Helen M KORCHAK, Keith TORNHEIM, Barbara E CORKEY and Aubrey E BOYD

Diabetes (New York, N.Y.), Vol.50(1), pp.56-62

2001

DOI: 10.2337/diabetes.50.1.56

PMID: 11147795

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Abstract

Glucagon-like peptide 1 (GLP-1) is the most potent physiological incretin for insulin secretion from the pancreatic beta-cell, but its mechanism of action has not been established. It interacts with specific cell-surface receptors, generates cAMP, and thereby activates protein kinase A (PKA). Many changes in pancreatic beta-cell function have been attributed to PKA activation, but the contribution of each one to the secretory response is unknown. We show here for the first time that GLP-1 rapidly released free fatty acids (FFAs) from cellular stores, thereby lowering intracellular pH (pHi) and stimulating FFA oxidation in clonal beta-cells (HIT). Similar changes were observed with forskolin, suggesting that stimulation of lipolysis was a function of PKA activation in beta-cells. Triacsin C, which inhibits the conversion of FFAs to long-chain acyl CoA (LC-CoA), enhanced basal FFA efflux as well as GLP-1-induced acidification and efflux of FFAs from the cell. Increasing the concentration of the lipase inhibitor orlistat progressively and largely diminished the increment in secretion caused by forskolin. However, glucose-stimulated secretion was less inhibited by orlistat and only at the highest concentration tested. Because the acute addition of FFAs also increases glucose-stimulated insulin secretion, these data suggest that the incretin function of GLP-1 may involve a major role for lipolysis in cAMP-mediated potentiation of secretion.

Fundamental and applied biological sciences. Psychology

Biological and medical sciences

Vertebrates: endocrinology

Morphology. Functional localizations

Endocrine pancreas

Details

Title: Subtitle: Glucagon-like peptide 1 stimulates lipolysis in clonal pancreatic β-cells (HIT)
Creators: Gordon C YANEY - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
Vildan N CIVELEK - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
Ann-Marie RICHARD - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
Joseph S DILLON - Division of Endocrinology, University of Iowa School of Medicine, Iowa City, Iowa, United States
Jude T DEENEY - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
James A HAMILTON - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
Helen M KORCHAK - Immunology Division, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
Keith TORNHEIM - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
Barbara E CORKEY - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
Aubrey E BOYD - Obesity Research Center, Boston Medical Center, Boston, Massachusetts, United States
Resource Type: Journal article
Publication Details: Diabetes (New York, N.Y.), Vol.50(1), pp.56-62
Publisher: American Diabetes Association
DOI: 10.2337/diabetes.50.1.56
PMID: 11147795
ISSN: 0012-1797
eISSN: 1939-327X
Language: English
Date published: 2001
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094602902771

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