EFFECTS OF ANGIOTENSIN-II ON INSULIN SENSITIVITY AND FASTING GLUCOSE-METABOLISM IN RATS

The hypothesis that angiotensin II (AII) might play a role in glucose homeostasis was studied in eight paired male littermate rats who had f asted for 16 h and were infused with either AII (50 ng/kg/min) or sali ne for 60 min. Mean arterial pressure (MAP) and plasma glucose (PG) di d not change significantly in the saline-infused rats. In the AII-infu sed rats, however, MAP increased by 14.1 +/- 1.3 mm Hg and PG increase d within 10 min to reach a new steady state that was approximately 10 mg/dL higher than the preinfusion PG (P < .001). Mean PG over 60 min w as significantly higher during AII infusion compared to saline infusio n (80.5 +/- 1 upsilon 70.4 +/- 0.7 mg/dL, P = .0354 by repeated measur es ANOVA), and plasma insulin was approximately 20 mu U/mL higher duri ng AII infusion (66 +/- 6 upsilon 46 +/- 2, P = .0023). Glucose turnov er rate, determined isotopically from a single bolus injection of [3-H -3]-glucose given after the new steady state was established, was no d ifferent in the two groups. However, insulin sensitivity declined by 3 3% in the AII-infused rats (0.116 +/- 0.012 upsilon 0.152 +/- 0.016, P = .047). It is concluded that AII infusion at a dose that results in a physiologic increase in blood pressure acutely induces a new steady state of insulin resistance, from either reduced glucose utilization d ue to vasoconstriction or increased hepatic glucose production. The re sult of the insulin resistance is an increase in plasma glucose levels , and hyperinsulinemia, which overcomes insulin resistance, returning glucose turnover to normal despite continuing AII infusion. This effec t of AII may be physiologically significant in the context of glucose homeostasis.