Y Saitoh1, W Hongwei, H Ueno, M Mizuta, M Nakazato. 1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Abstract
AIM: Angiotensin II receptor blockers (ARB) have been shown to lower insulin resistance in obese diabetic animal models and to reduce the risk of new-onset diabetes in hypertensive patients. In the present study, we studied whether telmisartan, an ARB with partial peroxisome proliferator-activated receptor-gamma (PPARgamma) activity, can exert a direct effect against fatty-acid-induced oxidative stress in pancreatic beta-cells. METHODS: The effect of telmisartan on lipotoxicity was evaluated using mouse insulin-secreting clonal MIN6 and isolated mouse pancreatic islet cells. Reactive oxygen species, protein kinase-C (PKC) activity and NAD(P)H oxidase activity were examined to clarify the underlying mechanisms. RESULT: Telmisartan decreased the accumulation of palmitate-induced reactive oxygen species in MIN6 cells by 25% and in mouse islet cells by 55%. Telmisartan also decreased palmitate-induced PKC activity by 36% and NAD(P)H oxidase activity by 32% in MIN6 cells. CONCLUSION: These findings indicate that telmisartan attenuated fatty-acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells. Our observations pave the way to the possible use of ARB as a means of protecting beta-cell survival and preserving insulin secretion capacity in patients with diabetes mellitus.
AIM: Angiotensin II receptor blockers (ARB) have been shown to lower insulin resistance in obese diabetic animal models and to reduce the risk of new-onset diabetes in hypertensivepatients. In the present study, we studied whether telmisartan, an ARB with partial peroxisome proliferator-activated receptor-gamma (PPARgamma) activity, can exert a direct effect against fatty-acid-induced oxidative stress in pancreatic beta-cells. METHODS: The effect of telmisartan on lipotoxicity was evaluated using mouseinsulin-secreting clonal MIN6 and isolated mouse pancreatic islet cells. Reactive oxygen species, protein kinase-C (PKC) activity and NAD(P)H oxidase activity were examined to clarify the underlying mechanisms. RESULT: Telmisartan decreased the accumulation of palmitate-induced reactive oxygen species in MIN6 cells by 25% and in mouse islet cells by 55%. Telmisartan also decreased palmitate-induced PKC activity by 36% and NAD(P)H oxidase activity by 32% in MIN6 cells. CONCLUSION: These findings indicate that telmisartan attenuated fatty-acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells. Our observations pave the way to the possible use of ARB as a means of protecting beta-cell survival and preserving insulin secretion capacity in patients with diabetes mellitus.
Authors: John A D'Elia; George Bayliss; Bijan Roshan; Manish Maski; Ray E Gleason; Larry A Weinrauch Journal: Int J Nephrol Renovasc Dis Date: 2010-12-22