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 fasted for 16 h and were infused with either AII (50 ng/kg/min) or saline for 60 min. Mean arterial pressure (MAP) and plasma glucose (PG) did not change significantly in the saline-infused rats. In the AII-infused rats, however, MAP increased by 14.1 +/- 1.3 mm Hg and PG increased 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 was significantly higher during AII infusion compared to saline infusion (80.5 +/- 1 v 70.4 +/- 0.7 mg/dL, P = .0354 by repeated measures ANOVA), and plasma insulin was approximately 20 mu U/mL higher during AII infusion (66 +/- 6 v 46 +/- 2, P = .0023). Glucose turnover rate, determined isotopically from a single bolus injection of [3-(3)H]-glucose given after the new steady state was established, was no different in the two groups. However, insulin sensitivity declined by 33% in the AII-infused rats (0.116 +/- 0.012 v 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 due to vasoconstriction or increased hepatic glucose production. The result 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.(ABSTRACT TRUNCATED AT 250 WORDS)