Hepatic Production of VLDL-Triglycerides. Dependence of Portal Substrate and Insulin Concentration

Abstract

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.

Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man.

“…This variability in response is understandable when the individual pathways are considered, because the total secretion rate after 24 h of carbohydrate hyperalimentation/hyperinsulinemia was a function of two opposing trends (Tables IV and V). The decreased secretion of preformed FA, coupled with an increase in de novo synthesis, could explain the conflicting results obtained in previous studies in which acute hyperinsulinemia either decreased (12,15,(50)(51)(52)(53) or did not affect (11, 54) VLDL secretion. Depending on the experimental factors, such as the selection of subjects, whether or not they were fasted, and in particular the duration and extent of hyperinsulinemia, the effect on one pathway may predominate.…”

Role of insulin in hepatic fatty acid partitioning: emerging concepts

“…Thus studies in humans have shown that intraportal infusion of insulin in humans results in a decrease in the secretion of VLDL-TAG [97]. Similarly, when humans are treated with insulin, the secretion of apoB "!!…”

Insulin regulates apolipoprotein B turnover and phosphorylation in rat hepatocytes.

“…Because both LDL cholesterol (3) and apo B 100 (4) levels are associated with atherosclerotic disease, an understanding of the control of hepatic apo B synthesis and secretion is important. Acute studies in man (5,6) suggest that insulin administration decreases hepatic secretion of VLDL. Using primary cultures of rat hepatocytes (7-1 1) and HepG2 cells (12,13), we (7,8) and others (9)(10)(11)(12)(13) have shown that insulin exposure for < 24 h inhibits the secretion of VLDL (8)(9)(10)(11)(12) and apo B (7,8,(11)(12)(13).…”