title: Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats.
abstract: OBJECTIVE
  Hypertension often coexists with insulin resistance. However, most metabolic effects of the antihypertensive agents have been investigated in nomotensive animals, in which different conclusions may arise. We investigated the metabolic effects of the new angiotensin II type 1 receptor blocker azilsartan using the obese Koletsky rats superimposed on the background of the spontaneously hypertensive rats.
  
  
  METHODS
  Male Koletsky rats were treated with azilsartan (2 mg/kg/day) over 3 weeks. Blood pressure was measured by tail-cuff. Blood biochemical and hormonal parameters were determined by enzymatic or ELISA methods. Gene expression was assessed by RT-PCR.
  
  
  RESULTS
  In Koletsky rats, azilsartan treatment lowered blood pressure, basal plasma insulin concentration and the homeostasis model assessment of insulin resistance index, and inhibited over-increase of plasma glucose and insulin concentrations during oral glucose tolerance test. These effects were accompanied by decreases in both food intake and body weight (BW) increase. Although two treatments showed the same effect on BW gain, insulin sensitivity was higher after azilsartan treatment than pair-feeding. Azilsartan neither affected plasma concentrations of triglyceride and free fatty acids, nor increased adipose mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and its target genes such as adiponectin, aP2. In addition, azilsartan downregulated 11β-hydroxysteroid dehydrogenase type 1 expression.
  
  
  CONCLUSIONS
  These results show the insulin-sensitizing effect of azilsartan in obese Koletsky rats. This effect is independent of decreases in food intake and BW increase or of the activation of adipose PPARγ. Our findings indicate the possible usefulness of azilsartan in the treatment of metabolic syndrome.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Ebihara
authors.forename: X
authors.initials: X
authors.lastname: Rong
authors.forename: K
authors.initials: K
authors.lastname: Hosoda
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D001794:Blood Pressure; D004797:Enzyme-Linked Immunosorbent Assay; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001786:Blood Glucose; D007328:Insulin; D010069:Oxadiazoles; D047495:PPAR gamma; C521273:azilsartan