Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans

Methodology for measuring plasma free fatty acid (FFA) turnover/oxidation with [1-¹⁴C]palmitate was tested in normal subjects. In study 1, two different approaches (720-min tracer infusion without prime vs. 150-min infusion with NaH¹⁴CO₃ prime) to achieve steady-state conditions of ¹⁴CO₂ yielded equivalent rates of plasma FFA turnover/oxidation. In study 2, during staircase NaH¹⁴CO₃ infusion, calculated rates of ¹⁴CO₂ appearance agreed closely with NaH¹⁴CO₃ infusion rates. In study 3, 300-min euglycemic insulin clamp documented that full biological effect of insulin on plasma FFA turnover/oxidation was established within 60-120 min. In study 4, plasma insulin concentration was raised to 14 ± 2, 23 ± 2, 38 ± 2, 72 ± 5, and 215 ± 10 μU/ml. A dose-dependent insulin suppression of plasma FFA turnover/oxidation was observed. Plasma FFA concentration correlated positively with plasma FFA turnover/oxidation in basal and insulinized states. Total lipid oxidation (indirect calorimetry) was significantly higher than plasma FFA oxidation in the basal state, suggesting that intracellular lipid stores contributed to whole body lipid oxidation. Hepatic glucose production and total glucose disposal showed the expected dose-dependent suppression and stimulation, respectively, by insulin. In conclusion, insulin regulation of plasma FFA turnover/oxidation is maximally manifest at low physiological plasma insulin concentrations, and in the basal state a significant contribution to whole body lipid oxidation originates from lipid pool(s) that are different from plasma FFA.