IMPAIRED INSULIN-INDUCED SYMPATHETIC NEURAL ACTIVATION AND VASODILATION IN SKELETAL-MUSCLE IN OBESE HUMANS

The sympathetic nervous system is an important regulatory mechanism of both metabolic and cardiovascular function, and altered sympathetic a ctivity may play a role in the etiology and/or complications of obesit y. In lean subjects, insulin evokes sympathetic activation and vasodil ation in skeletal muscle. In obese subjects such vasodilation is impai red and, in turn, may contribute to insulin resistance. To examine the relationship between sympathetic and vasodilatory responses in skelet al muscle to hyperinsulinemia, we simultaneously measured muscle sympa thetic nerve activity (MSNA) and calf blood flow at basal and during a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp in eight le an and eight obese subjects. The major findings of this study are twof old: obese subjects had a 2.2 times higher fasting rate of MSNA, and e uglycemic hyperinsulinemia, which more than doubled MSNA and increased calf blood flow by roughly 30% in lean subjects, had only a minor vas odilatory and sympathoexcitatory effect in obese subjects. In contrast , two non-insulin-sympathetic stimuli evoked comparably large increase s in MSNA in lean and obese subjects. We conclude that insulin resista nce in obese subjects is associated with increased fasting MSNA and a specific impairment of sympathetic neural responsiveness to physiologi cal hyperinsulinemia in skeletal muscle tissue.