Angiotensin 11 Increases Glucose Utilization during Acute Hyperinsulinemia via a Hemodynamic Mechanism

To determine whether hemodynamic changes can modulate in-sulin action in vivo, we administered angiotensin II (A,,) to nor-mal men under three separate, euglycemic conditions. First, in the presence of physiological hyperinsulinemia (- 115,U/ml), infusion of A,, at rates of 2, 10, and 20 ng/min per kg caused significant elevations of blood pressure, whole-body glucose clearance, and plasma insulin concentrations in an Al, dose-de-pendent manner. Second, in the presence of plasma insulin con-centrations that stimulate glucose transport maximally (-5,000,U/ml), A,, infusions increased whole-body glucose clearance without enhancing glucose extraction across the leg. Third, in the presence of basal insulin concentrations (.13 igU/ml), A,, infusions had no effect on whole-body glucose turn-over or leg glucose extraction. Thus, A,, enhanced whole-body glucose utilization without directly stimulating glucose trans-port in a major skeletal muscle bed. To evaluate a possible hemodynamic mechanism for the effects of A,, on glucose utili-zation, we measured blood flow to two areas that differ in their sensitivity to insulin: the kidneys and the leg. We found that A,, redistributed blood flow away from the predominantly insulin-independent tissues of the kidney and toward the insulin-sensi-tive tissues of the leg during both sham and hyperinsulinemic glucose clamps. The redistribution of flow had no effect on whole-body glucose turnover when leg glucose uptake was un-stimulated (sham clamps). However, when leg glucose uptake was activated by insulin, the redistribution of flow caused a net increase in whole-body glucose utilization. Our findings indi-cate that hemodynamic factors can modulate insulin action in vivo. Furthermore, our results suggest that variable activity of the renin-angiotensin system may contribute to inconsistencies in the association between insulin resistance and hypertension