title: Telmisartan, an angiotensin II type 1 receptor blocker, prevents the development of diabetes in male Spontaneously Diabetic Torii rats.
abstract: To assess the beneficial effects of the angiotensin II type 1 receptor blocker telmisartan on a non-obese animal model of reduced function and mass of islet beta-cells prior to the development of diabetes, Spontaneously Diabetic Torii (SDT) rats were treated with telmisartan at 8 weeks of age. At 24 weeks of age, the treatment with telmisartan dose-dependently ameliorated hyperglycemia and hypoinsulinemia, and high-dose (5 mg/kg/day) treated SDT rats did not developed diabetes. Real-time RT-PCR analysis revealed that treatment with high-dose telmisartan reduced mRNA expression of local renin-angiotensin system (RAS) components, components of NAD(P)H oxidase, transforming growth factor-beta1 and vascular endothelial growth factor in the pancreas of male SDT rats. Immunohistochemical and Western blot analyses revealed that treatment with telmisartan also reduced expression of p47(phox). These results suggest that treatment with telmisartan reduces oxidative stress by local RAS activation and protects against islet beta-cell damage and dysfunction. These findings provide at least a partial explanation for the reduced incidence of new-onset diabetes that has been observed in several clinical trials involving angiotensin II type 1 receptor blockers and ACE inhibitors.
authors.affiliation: Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan. goji@koto.kpu-m.ac.jp
authors.forename: Goji
authors.initials: G
authors.lastname: Hasegawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Fukui
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hosoda
authors.forename: Mai
authors.initials: M
authors.lastname: Asano
authors.forename: Ichiko
authors.initials: I
authors.lastname: Harusato
authors.forename: Muhei
authors.initials: M
authors.lastname: Tanaka
authors.forename: Emi
authors.initials: E
authors.lastname: Shiraishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Senmaru
authors.forename: Kazumi
authors.initials: K
authors.lastname: Sakabe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Jo
authors.initials: J
authors.lastname: Kitawaki
authors.forename: Aya
authors.initials: A
authors.lastname: Fujinami
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000187:drug effects / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D012333:RNA, Messenger; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D000077333:Telmisartan