Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects

The exact mechanisms for the decrease in R-R interval (RRI) during acute ph ysiological hyperinsulinemia with euglycemia are unknown. Power spectral an alysis of RRI and microneurographic recordings of muscle sympathetic nerve activity (MSNA) in 16 normal subjects provided markers of autonomic control during 90-min hyperinsulinemic/euglycemic clamps. By infusing propranolol and insulin (n = 6 subjects), we also explored the contribution of heighten ed cardiac sympathetic activity to the insulin-induced decrease in RRI. Sli ght decreases in RRI (P < 0.001) induced by sevenfold increases in plasma i nsulin could not be suppressed by propranolol. Insulin increased MSNA by mo re than twofold (P < 0.001), decreased the high-frequency variability of RR I (P < 0.01), but did not affect the absolute low-frequency variability of RRI. These results suggest that reductions in cardiac vagal tone and modula tion contribute at least in part to the reduction in RRI during hyperinsuli nemia. Moreover, more than twofold increases in MSNA occurring concurrently with a slight and not purely sympathetically mediated tachycardia suggest regionally nonuniform increases in sympathetic activity during hyperinsulin emia in humans.