Hepatic production of VLDL-triglycerides. Dependence of portal substrate and insulin concentration.

Insulin has an exacerbating effect on endogenous hypertriglyceridemia. Experiments were carried out in order to study the acute effects of insulin in 6 patients with endogenous hypertriglyceridemia and 6 controls. 0.1 Unit insulin/kg body weight was injected into the portal vein. Blood samples were taken from the portal and hepatic veins and analysed for FFA, glycerol, VLDL-triglycerides (VLDL-TG) and insulin. Liver blood flow was measured with cardiogreen. This technique allowed a study of the acute effect of insulin on the hepatic extraction of substrates and on the hepatic production of VLDL-TG. Under basal conditions the production of VLDL-TG in patients with endogenous hypertriglyceridemia was not statistically different from the production in controls. The results did not provide statistical proof of a correlation between the production and the hepatic uptake of VLDL-TG precursors; however, the production was negatively correlated to the hepatic clearance rate of insulin. During a one-hour observation period after the application of insulin, the production of VLDL-TG was decreased in controls and increased in patients with endogenous hypertriglyceridemia. The application of insulin was also followed by a decreased uptake of free fatty acids and glycerol, this change being similar in controls and in patients with endogenous hypertriglyceridemia. There was no correlation between the effect of insulin on the production of VLDL-TG and on the uptake of substrates by the liver. It is concluded that insulin has a direct effect on the production of VLDL-TG which is independent of substrate supply. The adverse effect of insulin in endogenous hypertriglyceridemia may reflect some type of impaired hepatic responsiveness to insulin.