%0 Journal Article
%T Glucagon-Like Peptide-1 Induced Signaling and Insulin Secretion Do Not Drive Fuel and Energy Metabolism in Primary Rodent Pancreatic ¦Â-Cells
%A Marie-Line Peyot
%A Joshua P. Gray
%A Julien Lamontagne
%A Peter J. S. Smith
%A George G. Holz
%A S. R. Murthy Madiraju
%A Marc Prentki
%A Emma Heart
%J PLOS ONE
%D 2009
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0006221
%X 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 ¦Â-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 ¦Â-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 [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 ¦Â-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 ¦Â-cell, and that the ¦Â-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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006221