Chronic Blockade of the Renin‐Angiotensin System Improves Glucose Tolerance in Insulin Resistant Rats

Blockade of the renin‐angiotensin‐system (RAS) has been shown to improve insulin resistance and prevent the onset of type 2 diabetes. However, the timing of the onset of the beneficial effects of angiotensin receptor blocker (ARB) is not clear. Therefore, we examined the effects of a 2 and an 11 week treatment with an ARB on fasting blood glucose (FBG) and glucose tolerance in pre‐diabetic, obese (OLETF) rats. An oral glucose tolerance test (oGTT) was used to evaluate the impairment of glucose tolerance in the following groups of rats: 1) untreated LETO (lean control strain), 2) untreated OLETF, 3) OLETF + ARB (ARB; 10 mg olmesartan/kg/d). Blood glucose was measured before and after 15, 30, 60 and 120 min of glucose administration. Before the start of ARB treatment OLETFs had a 50% increase in FBG compared to LETO. After 2 weeks of ARB there was no difference in FBG between OLETF and OLETF + ARB; however, after 11 weeks of treatment there was a 23% reduction in FBG between OLETF and OLETF + ARB. The response of oGTT increased 71% in OLETF compared to LETO. Two weeks after the start of ARB treatment, there was no difference in response between OLETF and OLETF + ARB; however, after 11 weeks of treatment there was a 30% reduction in the response of oGTT. These data suggest that chronic treatment with ARB is effective in alleviating the glucose intolerance associated with insulin resistance. Funded in part by NIH NCMHD 9T37MD001480.