A selective glucocorticoid receptor modulator (CpdA) attenuates cytokine-induced endoplasmic reticulum stress in β-cells.

ANDREONE, L; GIMENO, ML; BARCALA TABARROZZI, AE; ARIOLFO, L; ELÏAS, MJ; LIBERMAN, AC; GERLO, S; DE BOSSCHER, K; PERONE, MJ

Congreso; The 21st International Association of Pancreatology (IAP)/LAPSG Joint Meeting, Pancreas 2017; 2017

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that selectively destroys insulin producing β-cells. ER stress and subsequent insulin secretory deficiency in β-cells precede the onset of autoimmune diabetes. Pro-inflammatory cytokines (IL-1+IFN-; CYT) signaling leads to activation of ER stress in β-cells. We reported that Compound A (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride; CpdA), a dissociative glucocorticoid receptor (GR)-ligand, is an effective modulator of T and dendritic cells albeit in a GR-independent manner. Aim: to explore the beneficial effects of CpdA on cytokine-induced β-cell ER stress. Methods: NOD and NODscid mice; rat insulinoma INS-1E; Western blot; immune-fluorescence microscopy. Results: CpdA significantly reduced CYT-induced NO secretion by INS-1E cells (p