A glucocorticoid receptor modulator (Compound A) ameliorates cytokine-induced endoplasmic reticulum stress in insulin-producing cells.

PERONE, MARCELO JAVIER; ARIOLFO, LAURA; ANDREONE, LUZ; GIMENO, MARÍA LAURA; LIBERMAN, ANA C; FUERTES, FLORENCIA

Simposio; Frontiers in Bioscience 3; 2018

IBioBA-MPSP-CONICET

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-1b+IFN-g; 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. The aim of this study was to explore the beneficial effects of CpdA on CYT-induced β-cell ER stress; the classic GR-ligand dexamethasone was used for comparison. CpdA significantly reduced CYT-induced NO secretion by the insulinoma INS-1E cells (p