TIME-DEPENDENT EFFECTS OF INSULIN ON LIPID-SYNTHESIS IN CULTURED FETAL-RAT HEPATOCYTES - A COMPARISON BETWEEN LIPOGENESIS AND GLYCOGENESIS

The lipogenic effect of insulin was studied in 18-day-old fetal rat he patocytes after 2 to 3 days of culture in the presence of glucocortico ids when an acute stimulatory effect of insulin on glycogenesis was pr esent, The rate of [1-C-14]-acetate incorporation into lipids measured for 4 hours was much higher than with [U-C-14]-glucose (30 v 3.8 nmol /h/mg protein), The stimulatory effect of insulin on lipid labeling re mained weak (1.2-fold) and contrasted with its striking stimulatory ef fect on [U-C-14]-glucose incorporation into glycogen (fourfold), When lipid labeling was assessed in longer experiments, increasing acetate concentrations in the medium stimulated the incorporation rate of [1-C -14]-acetate into lipids (3.5-fold from 1 to 5 mmol/L after 36 hours) and decreased that of [U-C-14]-glucose (by twofold), The stimulatory e ffect of insulin on the rate of lipid labeling developed with both pre cursors from 12 to 36 hours after insulin exposure (by similar to twof old) independently of acetate concentration and was not glucocorticoid -dependent, contrary to the glycogenic response, Addition of a glucose load simultaneously with insulin increased the stimulation of lipogen esis when measured with [U-C-14]-glucose (twofold to 3.7-fold), Beside s contributing to an accumulation of larger and numerous lipid droplet s in the cells, insulin increased fatty acid synthase activity by 26%, whereas malic enzyme was not affected, Thus, insulin-dependent lipoge nesis in cultured fetal hepatocytes appears to be mostly regulated by a long-term mechanism, contrary to the glycogenic effect of insulin. C opyright (C) 1997 by W.B. Saunders Company.