Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cells
| Autor: | Joshua P. Gray, Marc Prentki, Emma Heart, George G. Holz, Peter K. Smith, S.R. Murthy Madiraju, Marie-Line Peyot, Julien Lamontagne |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_treatment lcsh:Medicine Diabetes and Endocrinology/Obesity Mice 0302 clinical medicine Glucagon-Like Peptide 1 Diabetes and Endocrinology/Endocrinology Insulin Secretion Biochemistry/Cell Signaling and Trafficking Structures Insulin Phosphorylation lcsh:Science Beta oxidation 0303 health sciences Multidisciplinary biology Adenine Nucleotides Diabetes and Endocrinology Oxidation-Reduction hormones hormone substitutes and hormone antagonists Research Article Signal Transduction medicine.medical_specialty endocrine system 030209 endocrinology & metabolism Carbohydrate metabolism Glucagon 03 medical and health sciences Islets of Langerhans Internal medicine medicine Lipolysis Animals Diabetes and Endocrinology/Type 2 Diabetes Rats Wistar Protein kinase A Protein kinase B 030304 developmental biology Esterification Venoms lcsh:R Rats Insulin receptor Endocrinology Glucose biology.protein Exenatide lcsh:Q Energy Metabolism Peptides Proto-Oncogene Proteins c-akt |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 7, p e6221 (2009) |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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