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Glucagon-like peptide 1 potentiates glucotoxicity-diminished insulin secretion via stimulation of cAMP-PKA signaling in INS-1E cells and mouse islets
- Source :
-
International Journal of Biochemistry & Cell Biology . Feb2013, Vol. 45 Issue 2, p483-490. 8p. - Publication Year :
- 2013
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Abstract
- Abstract: Glucagon-like peptide-1 (GLP-1)-enhanced insulin secretion is mainly mediated by cAMP-PKA and cAMP-Epac2 signaling pathways at physiological glucose concentrations. However the cellular mechanisms underlying the insulinotropic action of GLP-1 at glucotoxicity remain largely unknown. In the present study, we examined the effects of GLP-1 on glucotoxicity-diminished insulin secretion and explored the roles of these two cAMP-linked pathways in mediating the effects of GLP-1 under glucotoxic conditions. Consistent with the previous reports, exposure of INS-1E cells and mouse islets to 30mM glucose for 72h almost abolished glucose-stimulated insulin secretion. Addition of 10nM GLP-1 significantly increased glucose-stimulated insulin secretion. This was not due to a protective effect of GLP-1 against glucotoxicity-induced apoptosis but instead improvement of the secretory capacity of the insulin-secreting β-cells. It is of note that GLP-1 preferentially increased the expression and activity of PKA, whereas had no effects on Epac2 at high glucose. In correlation with the observations, treatment of INS-1E cells with the specific PKA inhibitor Rp-cAMPS completely abolished the insulinotropic action of GLP-1, whereas knock-down of Epac2 did not interfere the effects of GLP-1. Moreover, GLP-1 did not increase further insulin secretion in the presence of the PKA agonist 6-Bnz-cAMP-AM. By contrast, it produced additional enhancement of insulin secretion when Epac2 was maximally stimulated by its selective agonist 8-pCPT-2′-O-Me-cAMP-AM. Taken together, our results suggest that GLP-1 potentiates glucotoxicity-diminished insulin secretion mainly through cAMP-PKA signaling pathway. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 13572725
- Volume :
- 45
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- International Journal of Biochemistry & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 85009936
- Full Text :
- https://doi.org/10.1016/j.biocel.2012.11.016