title: [Candesartan improves insulin resistance induced by high-fat diet in rats].
abstract: OBJECTIVE
  To investigate the effects of candesartan, an angiotension II type I receptor antagonist, in improvement of insulin resistance (IR) induced by high-fat diet and the possible mechanism thereof.
  
  
  METHODS
  45 male Wistar rats were randomly divided into 3 groups: normal chow group (NC, n = 15) fed with normal diet, high fat diet group (HF, n = 15) fed with high fat diet, and high-fat diet with daily candesartan treatment group (HF + C, n = 15) fed with high fat diet and given orally with candesartan 8 mg/kg per day. Body weight was measured regularly. Four weeks later, oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp technique were performed to estimate the insulin sensitivity. After 12 h fasting blood samples were collected from the abdominal aorta to test the contents of blood glucose, and serum triglyceride (TG), total cholesterol (TC), LDL, HDL, and free fatty acid (FFA). Radioimmunoassay was used to detect the serum insulin. Viscera were taken out. Immunohistochemistry was used to examine the expression of peroxisome proliferation activated receptor (PPAR)-gamma in hepatic and adipose tissues.
  
  
  RESULTS
  The body weight 16 weeks later of the HF group was significantly higher than that of the HF + C group (P < 0.01). The liver weight and epididymal and peri-renal fat weights of the HF group were all significantly higher than those of the HF + C group and NC group (all P < 0.01). There was no significant difference in fasting blood sugar among these 3 groups (P > 0.05). The glucose levels 2 h after OGTT in the HF + C group was (6.3 +/- 0.5) mmol/L, significantly lower than that of the HF group [(7.3 +/- 1.2) mmol/L, P < 0.01]. The glucose infusion rate (GIR) of the HF + C group was (22 +/- 5) mmol/L, significantly higher than that of the HF group [(14 +/- 4) mmol/L, P < 0.01]. The PPARgamma expression levels in liver and adipose tissue of the HF + C group were up-regulated significantly compared with those of the HF group.
  
  
  CONCLUSIONS
  Candesartan may improve insulin resistance through promoting the expression of PPARgamma in liver and adipose tissue.
authors.affiliation: Department of Endocrinology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Yan
authors.forename: Jing-tao
authors.initials: JT
authors.lastname: Dou
authors.forename: Chang-yu
authors.initials: CY
authors.lastname: Pan
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Xue-min
authors.initials: XM
authors.lastname: Wang
authors.forename: Fang-ling
authors.initials: FL
authors.lastname: Ma
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Yang
authors.forename: Xian-ling
authors.initials: XL
authors.lastname: Wang
authors.forename: Yi-ming
authors.initials: YM
authors.lastname: Mu
authors.forename: Ju-ming
authors.initials: JM
authors.lastname: Lu
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004041:Dietary Fats; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004041:Dietary Fats; D007328:Insulin; D013777:Tetrazoles; C081643:candesartan