Effect of insulin on sterol and fatty acid synthesis and hydroxymethylglutaryl CoA reductase activity in mammalian cells grown in culture.

The effects of insulin on the synthesis of sterols and fatty acids and on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), a rate-limiting enzyme for sterol synthesis, were studied in mammalian cells grown in culture. While in some established cell lines sterol synthesis was not affected significantly by the hormone, in the nonpermanent human and animal cells the synthesis of lipids, especially that of sterols, as well as the activity of the reductase were stimulated following an incubation with insulin in a medium containing serum albumin for a few hours or longer. These effects of insulin were also demonstrable in the presence of solvent-extracted serum, which itself increases sterol synthesis and reductase activity. In medium containing whole serum insulin was ineffective. Addition of glucose decreased sterol synthesis as well as reductase activity. The effects of insulin were prevented by cycloheximide and are probably due to an increased synthesis of 3-hydroxy-3-methylglutaryl CoA reductase or of a protein that regulates its activity.