ACUTE HYPERINSULINEMIA DECREASES THE HEPATIC SECRETION OF VERY-LOW-DENSITY LIPOPROTEIN APOLIPOPROTEIN B-100 IN NIDDM

In a randomized crossover study, we measured the hepatic secretion rat e of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apoB) i n seven patients with well-controlled non-insulin-dependent diabetes m ellitus (NIDDM) (HbA(1) 8.4 +/- 0.4% [mean +/- SE]) on two occasions: during a 13-h hyperinsulinemic (plasma insulin concentration 586 +/- 9 .7 pmol/l) euglycemic (plasma glucose concentration 5.2 +/- 0.1 mmoV1) clamp; and during a 13-h saline (control) infusion, After 5 h of the hyperinsalinemic euglycemic clamp (or saline infusion) when a new stea dy state of apoB turnover was reached, [1-C-13]leucine was administere d by a primed (1 mg/kg), constant 8-h infusion (1 mg . kg(-1). h(-1)). VLDL apoB isotopic enrichment was determined with gas chromatography- mass spectrometry, and a monoexponential model was used to calculate t he fractional secretion rate of VLDL apoB, VLDL apoB secretion rate wa s significantly reduced during the hyperinsulinemic euglycemic clamp c ompared with the saline study (12.2 +/- 3.6 vs, 24.5 +/- 7.1 mg . kg(- 1). day(-1), P = 0.001), but there was no change in the fractional cat abolic rate of VLDL apoB, Concomitantly, plasma concentrations of none sterified fatty acids (NEFAs), glycerol, and triglycerides (TGs) were significantly lower during the hyperinsulinemic euglycemic clamp compa red with the saline study (NEFAs, P < 0.001; glycerol, P 0.005; TGs, P = 0.004), We conclude that acute hyperinsulinemia decreases the hepat ic secretion rate of VLDL apoB in NIDDM, probably in part due to reduc tion in the delivery of NEFA and glycerol substrate to the liver.