Hyperinsulinemia and Triglyceride-Rich Lipoproteins

Hypertriglyceridemia is the most frequent form of hyperlipidemia seen in diabetes. Because hypertriglyceridemia and hyperinsulinemia often coexist in the general population and because patients with NIDDM generally are hyperinsulinemic, we have undertaken a series of in vivo studies to examine the effects of hyperinsulinemia on VLDL production. These studies showed that chronic hyperinsulinemia is accompanied by increased VLDL production and that this occurs even when plasma free fatty acid (FFA) levels have fallen. By contrast, acute hyperinsulinemia is accompanied by a reduction in VLDL production, and this reduction is, at least in part, mediated by an associated reduction in the availability of plasma FFAs as a substrate for VLDL-triglyceride (TG). The studies also raise the possibility that the difference in the dependence of VLDL production on plasma FFAs in acute versus chronic hyperinsulinemia results from an increase in hepatic lipogenic enzymes and from the availability of an alternate substrate such as fructose. The overall effect of hyperinsulinemia on VLDL production is postulated to reflect both the effect of insulin on apolipoprotein B production and the hepatic synthesis of TG from either plasma FFAs or newly made fatty acids.