Effects of telmisartan and valsartan on insulin sensitivity in obese diabetic mice

• Published in: European Journal of Pharmacology Vol. 698; no. 1-3; pp. 505 - 510
• Main Authors: Ushijima, Kentarou, Takuma, Masashi, Ando, Hitoshi, Ishikawa-Kobayashi, Eiko, Nozawa, Masahiko, Maekawa, Tomohiro, Shiga, Tsuyoshi, Fujimura, Akio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.01.2013; Elsevier BV
• Subjects: Adiponectin; Adiponectin - blood; Adipose Tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; agonists; analogs & derivatives; angiotensin II; Angiotensin II type I receptor blocker; Animals; antagonists; Benzimidazoles; Benzimidazoles - pharmacology; Benzoates; Benzoates - pharmacology; blood; blood glucose; Body Weight; Body Weight - drug effects; Diabetes Mellitus; Diabetes Mellitus - blood; Diabetes Mellitus - genetics; Diabetes Mellitus - metabolism; Diabetes Mellitus - physiopathology; drug effects; Eating; Eating - drug effects; Fatty Acid Synthases; Fatty Acid Synthases - genetics; Fatty Acid-Binding Proteins; Fatty Acid-Binding Proteins - genetics; fatty-acid synthase; gene expression; Gene Expression Regulation; Gene Expression Regulation - drug effects; genes; genetics; Homeostasis; Homeostasis - drug effects; Inflammatory cytokine; insulin; Insulin Resistance; insulin tolerance test; Interleukin-6; Interleukin-6 - blood; Interleukin-6 - genetics; Male; messenger RNA; metabolism; Mice; Mice, Obese; Peroxisome proliferators-activator receptor-γ; pharmacology; physiopathology; PPAR gamma; PPAR gamma - agonists; PPAR gamma - metabolism; RNA, Messenger; RNA, Messenger - genetics; RNA, Messenger - metabolism; Telmisartan; Tetrazoles; Tetrazoles - pharmacology; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Valine; Valine - analogs & derivatives; Valine - pharmacology; Valsartan; Inflammatory cytokine; Peroxisome proliferators-activator receptor-γ; Adiponectin; Angiotensin II type I receptor blocker
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2012.11.022

Telmisartan and valsartan have angiotensin II receptor blocking activity. Because telmisartan has also an agonistic action for peroxisome proliferators-activator receptor (PPAR)-γ, it is speculated that an effect of telmisartan on insulin sensitivity is different from that of valsartan, which lacks of PPAR-γ agonistic activity. To address the issue, effects of telmisartan and valsartan on insulin sensitivity, adipocytokines and PPAR-γ target genes were evaluated in obese diabetic mice. KK-Ay mice were treated with telmisartan (5mg/kg) and valsartan (15mg/kg), once daily for 3 weeks. Insulin tolerance test was performed on day14, and plasma adiponectin concentration and mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in adipose tissues were measured on day 21. Time-course of plasma glucose level after the injection of insulin in mice with telmisartan was not significantly different from that of animals with valsartan. In addition, PPAR-γ antagonist did not diminished the improvement of insulin sensitivity by telmisartan. Telmisartan and valsartan elevated plasma adiponectin concentration and suppressed the mRNA expressions of TNF-α and IL-6 in adipose tissues. These variables of the telmisartan- and valsartan-treated groups did not significantly differ. Influence of telmisartan on the PPAR-γ target genes (ap2 and fatty acid synthase) mRNA expressions was not detected in adipose tissues under the present condition. These data suggest that the effect of telmisartan on insulin sensitivity is similar to that of valsartan, and a role of PPAR-γ-mediated stimuli is small in the telmisartan-induced improvement of insulin sensitivity.