ANGIOTENSIN-II INCREASES GLUCOSE-UTILIZATION DURING ACUTE HYPERINSULINEMIA VIA A HEMODYNAMIC MECHANISM

To determine whether hemodynamic changes can modulate insulin action i n vivo, we administered angiotensin II (A(II)) to normal men under thr ee separate, euglycemic conditions. First, in the presence of physiolo gical hyperinsulinemia (approximately 115 muU/ml), infusion of A(II) a t rates of 2, 10, and 20 ng/min per kg caused significant elevations o f blood pressure, whole-body glucose clearance, and plasma insulin con centrations in an A(II) dose-dependent manner. Second, in the presence of plasma insulin concentrations that stimulate glucose transport max imally (approximately 5,000 muU/ml), A(II) infusions increased whole-b ody glucose clearance without enhancing glucose extraction across the leg. Third, in the presence of basal insulin concentrations (approxima tely 13 muU/ml), A(II) infusions had no effect on whole-body glucose t urnover or leg glucose extraction. Thus, A(II), enhanced whole-body gl ucose utilization without directly stimulating glucose transport in a major skeletal muscle bed. To evaluate a possible hemodynamic mechanis m for the effects of A(II) on glucose utilization, we measured blood f low to two areas that differ in their sensitivity to insulin: the kidn eys and the leg. We found that A(II) redistributed blood flow away fro m the predominantly insulin-independent tissues of the kidney and towa rd the insulin-sensitive tissues of the leg during both sham and hyper insulinemic glucose clamps. The redistribution of flow had no effect o n whole-body glucose turnover when leg glucose uptake was unstimulated (sham clamps). However, when leg glucose uptake was activated by insu lin, the redistribution of flow caused a net increase in whole-body gl ucose utilization. Our findings indicate that hemodynamic factors can modulate insulin action in vivo. Furthermore, our results suggest that variable activity of the renin-angiotensin system may contribute to i nconsistencies in the association between insulin resistance and hyper tension.