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|a Peyot, Marie-Line
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|a Gray, Joshua P
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|a Lamontagne, Julien
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|a Smith, Peter J S
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|a Holz, George G
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|a Madiraju, S R Murthy
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|a Prentki, Marc
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|a Heart, Emma
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|a Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cells
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|c 2009-07.
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|z Get fulltext
|u https://eprints.soton.ac.uk/190273/1/pone.0006221.pdf
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|a 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/principal 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
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|a Article
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