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

• Published in: Diabetes & metabolism 2009-11, Vol.35 (5), p.392-397
• Main Authors: Saitoh, Y, Hongwei, W, Ueno, H, Mizuta, M, Nakazato, M
• Format: Article
• Language: English
• Subjects: Angiotensin II receptor blockers; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Benzimidazoles - pharmacology; Benzoates - pharmacology; Biological and medical sciences; Cellules β pancréatiques; Clone Cells; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose - administration & dosage; Glucose - metabolism; In Vitro Techniques; Inhibiteurs des récepteurs de l’angiotensine II; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - ultrastructure; Internal Medicine; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans - ultrastructure; Lipotoxicité; Medical sciences; Mice; Mice, Inbred C57BL; Microscopy, Confocal; NAD (P) H oxydase; NAD(P)H oxidase activity; NADPH Oxidases - metabolism; Oxidative stress; Oxidative Stress - drug effects; Palmitic Acid - toxicity; Pancreatic β cells; PKC; Protein Kinase C - metabolism; Reactive Oxygen Species - metabolism; Stress oxydant
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2009.04.005

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-γ (PPARγ) activity, can exert a direct effect against fatty-acid-induced oxidative stress in pancreatic β-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 β-cells. Our observations pave the way to the possible use of ARB as a means of protecting β-cell survival and preserving insulin secretion capacity in patients with diabetes mellitus.