title: Effects of telmisartan and valsartan on insulin sensitivity in obese diabetic mice.
abstract: 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-A(y) mice were treated with telmisartan (5mg/kg) and valsartan (15 mg/kg), once daily for 3 weeks. Insulin tolerance test was performed on day 14, 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.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Kentarou
authors.initials: K
authors.lastname: Ushijima
authors.forename: Masashi
authors.initials: M
authors.lastname: Takuma
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Eiko
authors.initials: E
authors.lastname: Ishikawa-Kobayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nozawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maekawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shiga
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004435:Eating / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D008820:Mice, Obese; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077333:Telmisartan; D013777:Tetrazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D052242:Adiponectin; D001562:Benzimidazoles; D001565:Benzoates; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D015850:Interleukin-6; D047495:PPAR gamma; D012333:RNA, Messenger; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000068756:Valsartan; D064429:Fatty Acid Synthases; D014633:Valine; D000077333:Telmisartan