Rh. Rao, EFFECTS OF ANGIOTENSIN-II ON INSULIN SENSITIVITY AND FASTING GLUCOSE-METABOLISM IN RATS, American journal of hypertension, 7(7), 1994, pp. 655-660
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.