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

Riccarda Granata, Fabio Settanni, Letizia Trovato, Davide Gallo, Iacopo Gesmundo, Rita Nano, Maria Pia Gallo, Loredana Bergandi, Marco Volante, Giuseppe Alloatti, Lorenzo Piemonti, Jérôme Leprince, Mauro Papotti, Hubert Vaudry, Huy Ong, Ezio Ghigo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2280-2393
Number of pages114
JournalDiabetes
Volume63
Issue number7
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Granata, R., Settanni, F., Trovato, L., Gallo, D., Gesmundo, I., Nano, R., Gallo, M. P., Bergandi, L., Volante, M., Alloatti, G., Piemonti, L., Leprince, J., Papotti, M., Vaudry, H., Ong, H., & Ghigo, E. (2014). RFamide peptides 43RFa and 26RFa both promote survival of pancreatic β-cells and human pancreatic islets but exert opposite effects on insulin secretion. Diabetes, 63(7), 2280-2393. https://doi.org/10.2337/db13-1522