Lipogenic and mitogenic effects of insulin during conversion of Ob17 cells to adipose-like cells.

Chronic exposure to insulin of confluent cells of a preadipocyte clonal line (Ob17) leads to an acceleration of their development into adipose cells. The short-term effects of insulin have been examined by the stimulation of [14C] alpha-aminoisobutyrate uptake and the long-term effects by the increase in the activity levels of several lipogenic enzymes and in the intracellular triacylglycerol content. These metabolic effects of insulin occur within a physiological range of concentrations (EC50 congruent to 1 nM). As compared to insulin, dose-response curves obtained with proinsulin on these parameters show at least a 10-fold decrease in sensitivity of the cells. In contrast, the growth-promoting effects of both insulin and proinsulin occur at supraphysiological concentrations (EC50 greater than 300 nM). This mitogenic response is likely mediated through binding to receptors of insulin-like growth factors. Our data demonstrate that long-term effects of insulin on lipid synthesis can be dissociated from its effect on cell growth. Therefore the Ob17 cell line should be a useful model to study the role of insulin in the regulation of lipid synthesis in adipose cells.