Telmisartan, an angiotensin II type 1 receptor blocker, prevents the development of diabetes in male Spontaneously Diabetic Torii rats.
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.
Hasegawa
Goji
G
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan. goji@koto.kpu-m.ac.jp
Fukui
Michiaki
M
Hosoda
Hiroko
H
Asano
Mai
M
Harusato
Ichiko
I
Tanaka
Muhei
M
Shiraishi
Emi
E
Senmaru
Takashi
T
Sakabe
Kazumi
K
Yamasaki
Masahiro
M
Kitawaki
Jo
J
Fujinami
Aya
A
Ohta
Mitsuhiro
M
Obayashi
Hiroshi
H
Nakamura
Naoto
N
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
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D012333:RNA, Messenger; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D000077333:Telmisartan