期刊
DIABETES & METABOLISM
卷 35, 期 5, 页码 392-397出版社
MASSON EDITEUR
DOI: 10.1016/j.diabet.2009.04.005
关键词
Angiotensin II receptor blockers; Pancreatic beta cells; Oxidative stress; PKC; NAD(P)H oxidase activity
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 (PPAR-gamma) 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. (C) 2009 Elsevier Masson SAS. All rights reserved.
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