An Angiotensin II (Ang II) Type 1 Receptor Blocker, Telmisartan, Improves Insulin Resistance in KK-Ay Diabetic Mice

Metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of diabetes and cardiovascular disease (CVD) in hypertensive patients. Further, recently, the interruption of the RAS has been shown to prevent the onset of diabetes in hypertensive patients. However, whether telmisartan, an angiotensin II type 1 receptor blocker (ARB) with selective peroxisome proliferator-activated receptor-γ (PPAR-γ) agonistic property could improve insulin sensitivity is not fully understood. In this study, we studied the effects of telmisartan on insulin sensitivity in KK-A(y) mice, an obese type 2 diabetic animal. Although there was no significant difference in body weight, food consumption, and glucose levels between the two groups, plasma insulin, triglycerides and non-esterified fatty acid levels were significantly decreased in telmisartan-treated KK-A(y) mice, compared with control KK-A(y) mice. The present findings suggest that telmisartan could exert a beneficial effect on insulin sensitivity in diabetic animals. Inhibition of the RAS by telmisartan, a selective agonist of PPAR-γ, may become a promising strategy for the treatment of hypertensive patients with metabolic syndrome and/or insulin resistance.