title: Candesartan cilexetil prevents diet-induced insulin resistance via peroxisome proliferator-activated receptor-γ activation in an obese rat model.
abstract: Angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been shown to reduce the incidence of type 2 diabetes mellitus; however, the underlying molecular mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of insulin and glucose metabolism, which improves insulin sensitivity. Whether candesartan cilexetil, as a prodrug of the AT1R blocker candesartan, has PPARγ-activating properties remains to be elucidated. The aim of the present study was to investigate the effects of oral administration of candesartan cilexetil on glucose tolerance and the actions of PPARγ on liver and adipose tissue in the insulin-resistant obese rat induced by high-fat diet. Animals treated with candesartan cilexetil showed an improved glucose tolerance after oral glucose challenge. Whole-body insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique. During high-fat feeding in high-fat diet (HF) rats, the glucose infusion rate (GIR) was 52.3% lower than that in normal chow (NC) rats. However, the GIR was significantly enhanced following candesartan cilexetil treatment. Angiotensin II receptor antagonism also resulted in significant increases in PPARγ protein expression in adipose and liver tissue. These results indicate that PPARγ activation by candesartan cilexetil may provide novel therapeutic options in the treatment of patients with metabolic syndrome.
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Yan
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Pan
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Jing-Tao
authors.initials: JT
authors.lastname: Dou
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Meng
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Mu
keywords: angiotensin II; angiotensin II type 1 receptor blockers; insulin resistance; peroxisome proliferator-activated receptor γ