Coordinate roles of insulin and glucose on the growth of hepatoma cells in culture.

Abstract

The growth-promoting effect of insulin on cells in culture is well established. In addition, most cells need glucose for growth, although hepatic cells, which have an active gluconeogenic pathway, can survive in glucose-free medium. Since insulin can inhibit gluconeogenesis, we have studied the effect of insulin on the growth of a well differentiated hepatoma cell line (Fao) in glucose-containing and glucose-free medium. In the presence of glucose, Fao cells had a doubling time of 26 h, and insulin stimulated cell growth in a concentration-dependent manner. Half-maximal stimulation occurred at physiological concentrations (3 × 10−11 m), and a maximal effect was observed at 10−8 m, with a 9-fold increase in total cell number after 6-14 days. In contrast, when glucose was omitted from the culture medium, the hepatoma cells grew slower (doubling time, 38 h), and insulin inhibited cell growth by up to 80%. The doseresponse curve for inhibition was similar to that for stimulation. Inhibition of growth correlat...