Angiotensin II induces insulin resistance independent of changes in interstitial insulin

We set out to examine whether angiotensin-driven hypertension can alter ins ulin action and whether these changes are reflected as changes in interstit ial insulin (the signal to which insulin-sensitive cells respond to increas e glucose uptake). To this end, we measured hemodynamic parameters, glucose turnover, and insulin dynamics in both plasma and interstitial fluid (lymp h) during hyperinsulinemic euglycemic clamps in anesthetized dogs, with or without simultaneous infusions of angiotensin II (ANG II). Hyperinsulinemia per se failed to alter mean arterial pressure, heart rate, or femoral bloo d flow ANG II infusion resulted in increased mean arterial pressure (68 +/- 16 to 94 +/- 14 mmHg, P < 0.001) with a compensatory decrease in heart rat e (110 +/- 7 vs. 86 +/- 4 mmHg, P < 0.05). Peripheral resistance was signif icantly increased by ANG II from 0.434 to 0.507 mmHg.ml(-1).min (P < 0.05). ANG IT infusion increased femoral artery blood flow (176 +/- 4 to 187 +/- 5 ml/min, P < 0.05) and resulted in additional increases in both plasma and lymph insulin (93 +/- 20 to 122 +/- 13 mu U/ml and 30 +/- 4 to 45 +/- 8 mu U/ml, P < 0.05). However, glucose uptake was not significantly altered and actually had a tendency to be lower (5.9 +/- 1.2 vs. 5.4 +/- 0.7 mg.kg(-1) .min(-1), P > 0.10). Mimicking of the ANG II-induced hyperinsulinemia resul ted in an additional increase in glucose uptake. These data imply that ANG II induces insulin resistance by an effect independent of a reduction in in terstitial insulin.