Effect of age on insulin stimulation of sympathetic nervous system activity in man

Previous studies have shown that oral glucose increases plasma norepinephrine (NE) in man, an effect which is more pronounced in the elderly. Recently we have shown that hyperinsulinemia results in a dose-dependent increase in sympathetic nervous system (SNS) activity in young men independent of changes in blood glucose. We now report studies of the influence of hyperinsulinemia on SNS activity in healthy elderly. Euglycemic glucose clamp studies were performed at 2 insulin infusion rates, 2 mU/kg/min (young 22-37 yr, n = 7; old 63-77 yr, n = 9) and 5 mU/kg/min (young 22-36 yr, n = 7; old 64-75 yr, n = 5) nonobese men. Control studies were performed in 5 young and 3 old subjects. In control studies there were no significant changes in NE or cardiovascular measures in either group. Insulin infusion at 2 mU/kg/min in young subjects was associated with significant increases in NE, (p < 0.001) pulse (p < 0.05), pulse pressure (p < 0.005) and double product (pulse × systolic pressure) (p < 0.01). In contrast 2 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to an increase in pulse pressure (p < 0.01). The changes in NE at this insulin infusion dose were greater in the young than in the old (p < 0.005). Insulin infusion at 5 mU/kg/min in young subjects were associated with significant increases in NE, (p < 0.001) mean arterial blood pressure (MABP) (p < 0.001), pulse pressure (p < 0.001) and double product (p < 0.001). In contrast 5 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to a decrease in MABP (p < 0.001) only. The change in NE and MABP at this insulin infusion dose were greater in the young than in the old (p < 0.001) for each). In the young group the increases in NE were greater during the 2 mU/kg/min studies than in the control studies (p < 0.001) and the increases in NE during the 5 mU/kg/min studies were greater than during the 2 mU/kg/min studies (p < 0.001). In the old group there were no differences in NE or cardiovascular measures between the control, 2 mU or 5 mU insulin infusions. These studies indicate diminished insulin-induced SNS activation in the elderly. The disparity in the elderly between the enhanced SNS response to oral glucose and the blunted response to intravenous insulin and glucose suggests that splanchnic factors may mediate the SNS activation after oral glucose.