EFFECTS OF INSULIN AND GLUCAGON ON THE SECRETION OF APOLIPOPROTEIN B-CONTAINING LIPOPROTEINS AND TRIACYLGLYCEROL SYNTHESIS BY HUMAN HEPATOMA (HEP G2) CELLS

A human, hepatoma-derived cell line (Hep G2) was used to investigate t he primary effect of insulin and glucagon on the hepatic secretion of apolipoprotein B (apoB). Insulin caused a concentration-dependent decr ease in the rate of apoB secretion into the culture medium (0.60+/-0.0 3 mu g apoB/hr/mg cell protein, no insulin to 0.31+/-0.03 at 10(-7)M i nsulin, p<0.001). Glucagon (10(-7)M to 10(-11)M) also decreased apoB s ecretion in a dose-dependent manner. This effect was less marked than with insulin when glucose was the substrate. When apoB secretion was s timulated with oleic acid (0.4mM), however, both hormones inhibited th e process equally. A single addition of 10(-9)M of either hormone inhi bited apoB secretion for at least 72 hr. After incubation with either insulin or glucagon alone for 48 hr, addition of the other hormone sup pressed apoB secretion further. When both hormones were added in combi nation at the outset, however, there was no additive effect. [H-3]-Gly cerol incorporation into cellular TG was decreased 20% by both insulin and glucagon (10(-9)M). Thus both insulin and glucagon inhibit the se cretion of apoB by cultured Hep G2 cells. There was no evidence to sug gest that the effect of either hormone changed to become stimulatory w ith prolonged incubation. Our findings may explain in part the effect of both hormones in lowering serum concentrations of triacylglycerol-r ich lipoproteins and the hyper-triacylglycerolaemia which frequently a ccompanies states of insulin deficiency and insulin resistance.