METABOLIC BASIS OF HYPOTRIGLYCERIDEMIC EFFECTS OF INSULIN IN NORMAL MEN

The mechanism by which acute insulin administration alters VLDL apolip oprotein (ape) B subclass metabolism and thus plasma triglyceride conc entration was evaluated in 7 normolipidemic healthy men on two occasio ns, during a saline infusion and during an 8.5-hour euglycemic hyperin sulinemic clamp (serum insulin, 490+/-30 pmol/L). During the insulin i nfusion, plasma triglycerides decreased by 22% (P<.05), and serum free fatty add decreased by 85% (P<.05). The plasma concentration of VLDL1 apo B fell 32% during the insulin infusion, while that of VLDL2 apo B remained constant. A bolus injection of [3-H-2]leucine was given on b oth occasions to trace apo B kinetics in the VLDL1 and VLDL2 subclasse s (Svedberg flotation rate, 60-400 and 20-60, respectively), and the k inetic basis for the: change in VLDL levels caused by insulin was exam ined using a non-steady-state multicompartmental model. The mean rate of VLDL1 apo B synthesis decreased significantly by 35% (P<.05) after 0.5 hour of the insulin infusion (523+/-87 mg/d) compared with the sal ine infusion (808+/-91 mg/d). This parameter was allowed to van with t ime to explain the fall in VLDL1 concentration. After 8.5 hours of hyp erinsulinemia, the rate of VLDL1 apo B synthesis was 51% lower (321+/- 105 mg/d) than during the saline infusion (651+/-81 mg/d, P<.05). VLDL 2 apo B production was similar during the saline (269+/-35 mg/d) and i nsulin (265+/-37 mg/d) infusions. No significant changes were observed in the fractional catabolic rates of either VLDL1 or VLDL2 apo B. We conclude that acute hyperinsulinemia lowers plasma triglyceride and VL DL levels principally by suppressing VLDL1 apo B production but has no effect on VLDL2 apo B production. These findings indicate that the ra tes of VLDL1 and VLDL2, apo B production in the liver are independentl y regulated.