Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats
Article first published online: 27 OCT 2011
© 2011 Blackwell Publishing Ltd
Diabetes, Obesity and Metabolism
Volume 13, Issue 12, pages 1123–1129, December 2011
How to Cite
Zhao, M., Li, Y., Wang, J., Ebihara, K., Rong, X., Hosoda, K., Tomita, T. and Nakao, K. (2011), Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. Diabetes, Obesity and Metabolism, 13: 1123–1129. doi: 10.1111/j.1463-1326.2011.01471.x
- Issue published online: 27 OCT 2011
- Article first published online: 27 OCT 2011
- Accepted manuscript online: 12 JUL 2011 12:00AM EST
- Date submitted 25 April 2011; date of first decision 25 May 2011; date of final acceptance 7 July 2011
- angiotensin II type 1 receptor;
- peroxisome proliferator-activated receptor
Aim: 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.