Insulin regulation of regional free fatty acid metabolism

Studies were conducted to determine whether regional free fatty acid (FFA) release is differentially regulated by insulin. Systemic, leg, and splanchnic palmitate rate of appearance ([9,10-³H]palmitate) was measured in 26 healthy adults using the euglycemic-hyperinsulinemic clamp technique to achieve a physiological range of plasma insulin concentrations. We found that insulin inhibited systemic, leg, and splanchnic palmitate release in a dose- dependent fashion over the range of insulin infused (0-1.0 mU · kg^-1 · min^-1). Progressive hyperinsulinemia changed the leg from a net producer to a net FFA consumer, whereas the splanchnic bed converted from a net FFA consumer to a net producer. At the 0.5 mU · kg^-1 · min^-1 insulin infusion rate, leg FFA release was almost completely suppressed, whereas even with the 1.0 mU · kg^-1 · min^-1 insulin infusion rate, splanchnic FFA release decreased by only ~65% (P < 0.05 leg vs. splanchnic). These results demonstrate the regional heterogeneity of insulin-regulated FFA release in vivo, and indicate that visceral adipose tissue lipolysis is more resistant to insulin suppression than is leg lipolysis in humans.