Format

Send to

Choose Destination
PLoS One. 2009 Jul 13;4(7):e6221. doi: 10.1371/journal.pone.0006221.

Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cells.

Author information

1
Molecular Nutrition Unit and Montreal Diabetes Research Center at the Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Department of Nutrition and Biochemistry, Université de Montréal, Montréal, Quebec, Canada.

Abstract

BACKGROUND:

Glucagon like peptide-1 (GLP-1) and its analogue exendin-4 (Ex-4) enhance glucose stimulated insulin secretion (GSIS) and activate various signaling pathways in pancreatic beta-cells, in particular cAMP, Ca(2+) and protein kinase-B (PKB/Akt). In many cells these signals activate intermediary metabolism. However, it is not clear whether the acute amplification of GSIS by GLP-1 involves in part metabolic alterations and the production of metabolic coupling factors.

METHODOLOGY/PRINICIPAL FINDINGS:

GLP-1 or Ex-4 at high glucose caused release (approximately 20%) of the total rat islet insulin content over 1 h. While both GLP-1 and Ex-4 markedly potentiated GSIS in isolated rat and mouse islets, neither had an effect on beta-cell fuel and energy metabolism over a 5 min to 3 h time period. GLP-1 activated PKB without changing glucose usage and oxidation, fatty acid oxidation, lipolysis or esterification into various lipids in rat islets. Ex-4 caused a rise in [Ca(2+)](i) and cAMP but did not enhance energy utilization, as neither oxygen consumption nor mitochondrial ATP levels were altered.

CONCLUSIONS/SIGNIFICANCE:

The results indicate that GLP-1 barely affects beta-cell intermediary metabolism and that metabolic signaling does not significantly contribute to GLP-1 potentiation of GSIS. The data also indicate that insulin secretion is a minor energy consuming process in the beta-cell, and that the beta-cell is different from most cell types in that its metabolic activation appears to be primarily governed by a "push" (fuel substrate driven) process, rather than a "pull" mechanism secondary to enhanced insulin release as well as to Ca(2+), cAMP and PKB signaling.

PMID:
19593440
PMCID:
PMC2704866
DOI:
10.1371/journal.pone.0006221
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center