Insulin and Sympathoexcitation: It Is Not All in Your Head

Abstract

Obesity and weight gain are frequently associated with increases in blood pressure, driven in part by sympathoexcitation (1). Obesity also is linked with insulin resistance and is associated with ongoing public health concerns, including the so-called metabolic syndrome (2). Even small increases in plasma insulin concentration (as low as one-fifth of that achieved after a mixed meal) (3) have marked and potentially long-lasting sympathoexcitatory effects (4). Such findings have important implications for the fluctuations in circulating catecholamines and blood pressure that occur in the postprandial state, as well as for conditions with sustained hyperinsulinemia. Yet the question remains, what are the mechanisms driving sympathoexcitation with hyperinsulinemia? In human studies, a systemic infusion of insulin has been shown to result in a gradual increase in muscle sympathetic nerve activity that remains elevated after plasma levels return to baseline (5). This finding supports the idea that insulin-mediated sympathoexcitation is the result of a central mechanism, requiring time for insulin to pass through the blood-brain barrier. Along these lines, recent data from animals suggest insulin acts within the arcuate nucleus to increase sympathetic activity via pathways including the paraventricular nucleus of the hypothalamus and the rostral ventrolateral medulla (6–8). These new ideas have important implications for the myriad of disorders related …