Angiotensin II induces insulin resistance independent of changes in interstitial insulin

Richey, Joyce M., Marilyn Ader, Donna Moore, and Richard N. Bergman. Angiotensin II induces insulin resistance independent of changes in interstitial insulin. Am. J. Physiol. 277 (Endocrinol. Metab. 40): E920-E926, 1999.--We set out to examine whether angiotensin-driven hypertension can alter insulin action and whether these changes are reflected as changes in interstitial insulin (the signal to which insulin-sensitive cells respond to increase glucose uptake). To this end, we measured hemodynamic parameters, glucose turnover, and insulin dynamics in both plasma and interstitial fluid (lymph) 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 blood flow. ANG II infusion resulted in increased mean arterial pressure (68 [+ or -] 16 to 94 [+ or -] 14 mmHg, P [is less than] 0.001) with a compensatory decrease in heart rate (110 [+ or -] 7 vs. 86 [+ or -] 4 [+ or -], P [is less than] 0.05). Peripheral resistance was significantly increased by ANG II from 0.434 to 0.507 mmHg [multiplied by] [ml.sup.-1] [multiplied by] min (P [is less than] 0.05). ANG II infusion increased femoral artery blood flow (176 [+ or -] 4 to 187 [+ or -] 5 ml/min, P [is less than] 0.05) and resulted in additional increases in both plasma and lymph insulin (93 [+ or -] 20 to 122 [+ or -] 13 [micro]U/ml and 30 [+ or -] 4 to 45 [+ or -] 8 [micro]U/ml, P [is less than] 0.05). However, glucose uptake was not significantly altered and actually had a tendency to be lower (5.9 [+ or -] 1.2 vs. 5.4 [+ or -] 0.7 mg [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1], P [is less than] 0.10). Mimicking of the ANG II-induced hyperinsulinemia resulted in an additional increase in glucose uptake. These data imply that ANG II induces insulin resistance by an effect independent of a reduction in interstitial insulin. lymph insulin; euglycemic hyperinsulinemia; endogenous glucose production; blood flow