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Diabetes. 2014 Jul;63(7):2380-93. doi: 10.2337/db13-1522. Epub 2014 Mar 12.

RFamide peptides 43RFa and 26RFa both promote survival of pancreatic β-cells and human pancreatic islets but exert opposite effects on insulin secretion.

Author information

1
Division of Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences, University of Torino, Torino, Italy riccarda.granata@unito.it.
2
Division of Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences, University of Torino, Torino, Italy.
3
Diabetes Research Institute, Division of Immunology, Transplantation, and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
4
Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy.
5
Department of Oncology, University of Torino, Torino, Italy.
6
Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, International Associated Laboratory Samuel de Champlain, Institute for Research and Innovation in Biomedicine, INSERM U-982, University of Rouen, Rouen, France.
7
Faculty of Pharmacy, University of Montréal, Montréal, Québec, Canada.

Abstract

RFamide peptides 43RFa and 26RFa have been shown to promote food intake and to exert different peripheral actions through G-protein-coupled receptor 103 (GPR103) binding. Moreover, 26RFa was found to inhibit pancreatic insulin secretion, whereas the role of 43RFa on β-cell function is unknown, as well as the effects of both peptides on β-cell survival. Herein, we investigated the effects of 43RFa and 26RFa on survival and apoptosis of pancreatic β-cells and human pancreatic islets. In addition, we explored the role of these peptides on insulin secretion and the underlying signaling mechanisms. Our results show that in INS-1E β-cells and human pancreatic islets both 43RFa and 26RFa prevented cell death and apoptosis induced by serum starvation, cytokine synergism, and glucolipotoxicity, through phosphatidylinositol 3-kinase/Akt- and extracellular signal-related kinase 1/2-mediated signaling. Moreover, 43RFa promoted, whereas 26RFa inhibited, glucose- and exendin-4-induced insulin secretion, through Gαs and Gαi/o proteins, respectively. Inhibition of GPR103 expression by small interfering RNA blocked 43RFa insulinotropic effect, but not the insulinostatic action of 26RFa. Finally, 43RFa, but not 26RFa, induced cAMP increase and glucose uptake. In conclusion, because of their survival effects along with the effects on insulin secretion, these findings suggest potential for 43RFa and 26RFa as therapeutic targets in the treatment of diabetes.

PMID:
24622796
DOI:
10.2337/db13-1522
[Indexed for MEDLINE]
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