Acute Treatment with Candesartan Cilexetil, an Angiotensin II Type 1 Receptor Blocker, Improves Insulin Sensitivity in High-Fructose-Diet-fed Rats

Abstract

We aimed to determine whether acute treatment with candesartan cilexetil (CV-11974), an angiotensin II type 1 receptor blocker (ARB) can improve insulin sensitivity in high-fructose-diet (HFD)-fed rats. In vivo glucose utilization was measured by applying the euglycemic clamp technique and the expression levels of insulin-signaling molecules in skeletal muscles were examined by western blotting. A bolus injection of CV-11974 improved the glucose infusion rate (GIR) of HFD-fed rats to the level of the control rats. Furthermore, restoration of impaired tyrosine phosphorylation of insulin receptor (IR) β, Akt phosphorylation at Ser⁴⁷³ and Thr³⁰⁸, and phosphorylation of the 160-kDa Akt substrate (AS160) in the skeletal muscles of HFD-fed rats were achieved by this treatment. These results suggest that acute administration of candesartan cilexetil can increase insulin sensitivity of HFD-fed rats, which is associated with improved insulin signaling in skeletal muscles.

Key words

insulin sensitivity - angiotensin II type 1 receptor blocker - high-fructose diet - euglycemic clamp - insulin signaling

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