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

TitleGlucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cells
Publication TypeJournal Article
Year of Publication2009
AuthorsPeyot M.L, Gray J.P, Lamontagne J., Smith P.J, Holz G.G, Madiraju S.R, Prentki M., Heart E.
JournalPLoS OnePLoS One
Volume4
Paginatione6221
ISBN Number1932-6203 (Electronic)<br/>1932-6203 (Linking)
Accession Number19593440
KeywordsAdenine Nucleotides/metabolism, Animals, Energy Metabolism, Esterification, Glucagon-Like Peptide 1/*pharmacology, Glucose/administration & dosage, Insulin/*secretion, Islets of Langerhans/*drug effects/metabolism/secretion, Male, Mice, Oxidation-Reduction, Peptides/pharmacology, Phosphorylation, Proto-Oncogene Proteins c-akt/metabolism, Rats, Rats, Wistar, Signal Transduction/*drug effects, Venoms/pharmacology
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.