Candesartan attenuates fatty acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic β-cells

Angiotensin II receptor blockers (ARBs) have been shown to decrease insulin resistance in obese diabetic animal models and reduce the risk of new-onset diabetes in hypertensive patients In the present study, we studied whether candesartan, an ARB, can exert a direct effect against fatty acid-induced oxidative stress in pancreatic beta-cells The effect of candesartan on lipotoxicity was evaluated using mouse insulin-secreting clonal cell, MIN6 and isolated mouse pancreatic islets. Intracellular insulin and triglyceride content, uncoupling protein-2 (UCP-2) mRNA expression, reactive oxygen species, protein kinase C (PKC) and NAD(P)H oxidase activity were examined Candesartan recovered decreased insulin content in MIN6 exposed to 25 mM glucose with 0 5 mM palmitate (P < 0 01) Candesartan tended to decrease intracellular triglyceride accumulation in cells exposed to 25 mM glucose with 0 5 mM palmitate Palmitate-induced up-regulation of UCP-2 mRNA levels was suppressed by candesartan in a dose-dependent manner Candesartan decreased palmitate-induced reactive oxygen species accumulation in MIN6 cells by 23% and in mouse islets by 59% Candesartan also decreased palmitate-induced PKC activity by 21% and NAD(P)H oxidase activity by 37% in MIN6 cells These findings indicated that candesartan attenuated fatty acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells (C) 2010 Published by Elsevier Ireland Ltd