EFFECTS OF ACUTE HYPERINSULINEMIA ON VLDL TRIGLYCERIDE AND VLDL APO-BPRODUCTION IN NORMAL-WEIGHT AND OBESE INDIVIDUALS

The effects of short-term hyperinsulinemia on the production of both V LDL triglyceride and VLDL apoB were determined semiquantitatively befo re and during a 6-h euglycemic hyperinsulinemic clamp (40 MU. m-2 . mi n-1) in 17 women (8 chronically hyperinsulinemic obese, BMI = 35.7 kg/ m2; 9 normal weight, BMI = 22.5 kg/m2). During acute hyperinsulinemia, plasma FFA decreased by approximately 95% within 1 h in both groups. VLDL triglyceride production decreased 66% in the control subjects (P = 0.0003) and 67% in obese subjects (P = 0.0003). ApoB production decr eased 53% in control subjects (P = 0.03) but only 8% in obese (NS). Pl asma triglycerides decreased by 40% from baseline in control subjects (P < 0.0001) but only by 10% in obese subjects (P = NS). Despite the s imilar decrease in triglyceride and apoB production in control subject s, VLDL particle size (triglyceride-to-apoB ratio) decreased with hype rinsulinemia (P = 0.003). In obese subjects, despite a decrease in tri glyceride production similar to that in control subjects but no change in apoB production, VLDL size did not change appreciably. Acute hyper insulinemia in humans 1) suppresses plasma FFA equally in control and obese subjects at this high dose of insulin; 2) inhibits VLDL triglyce ride production equally in control and obese subjects, perhaps seconda ry to the decrease in FFA; 3) inhibits VLDL apoB production in control but less so in obese subjects, suggesting that obese subjects may be resistant to this effect of insulin; 4) decreases plasma triglyceride and VLDL particle size in control subjects, reflecting either stimulat ion of LPL activity or a greater relative decrease in triglyceride to apoB production; and 5) does not decrease plasma triglyceride or VLDL size in obese subjects to the same extent as it does in control subjec ts. Thus, the insulin resistance of obesity affects some but not all a spects of VLDL metabolism.