TITLE

Glucagon-Like Peptide-1 Induced Signaling and Insulin Secretion Do Not Drive Fuel and Energy MetaBolism in Primary Rodent Pancreatic β-Cells

AUTHOR(S)
Peyot, Marie-Line; Gray, Joshua P.; Lamontagne, Julien; Smith, Peter J. S.; Holz, George G.; Madiraju, S. R. Murthy; Prentki, Marc; Heart, Emma
PUB. DATE
July 2009
SOURCE
PLoS ONE;2009, Vol. 4 Issue 7, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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 b-cells, in particular cAMP, Ca2+ 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 (∼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 bcell 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 [Ca2+]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 b-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 b-cell, and that the b-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 Ca2+, cAMP and PKB signaling.
ACCESSION #
58518866

 

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