SUMOylation protects against IL-1{beta}-induced apoptosis in INS-1 832/13 cells and human islets

We examined insulin secretion, intracellular Ca2+ responses, induction of endoplasmic reticulum stress markers and inducible nitric oxide synthase (iNOS) expression, and apoptosis by TUNEL and caspase 3 cleavage. Surprisingly, upregulation of SENP1 reduces insulin secretion and impairs intracellular Ca2+ handling. This secretory dysfunction is due to SENP1-induced cell death. Indeed, the detrimental effect of SENP1 on secretory function is diminished when two mediators of β-cell death, iNOS and NF-B, are pharmacologically inhibited. Conversely, enhanced SUMOylation protects against IL-1β-induced cell death. This is associated with reduced iNOS expression, cleavage of caspase 3, and nuclear translocation of NF-B. Taken together, these findings identify SUMO1 as a novel antiapoptotic protein in islets and demonstrate that reduced viability accounts for impaired islet function following SENP1 up-regulation.

Source: AJP: Endocrinology and Metabolism - October 15, 2014 Category: Endocrinology Authors: Hajmrle, C., Ferdaoussi, M., Plummer, G., Spigelman, A. F., Lai, K., Manning Fox, J. E., MacDonald, P. E. Tags: Articles Source Type: research