Glucagon inhibits phosphatidylcholine biosynthesis via the CDP-choline and transmethylation pathways in cultured rat hepatocytes

The short-term influence of insulin and glucagon on phosphatidylcholine biosynthesis in monolayer cultures of rat hepatocytes was investigated. Under conditions in which insulin (100 nM) stimulated [3H]acetate incorporation into fatty acid almost twofold, synthesis of phosphatidylcholine via CDP-choline and from phosphatidylethanolamine were unaffected. By contrast, glucagon (100 nM), even in the presence of insulin (100 nM), reduced the rate of phosphatidylcholine formation from [Me-3H]phosphocholine by approximately 25% (p less than 0.05) within 1 h. Similarly, [3H]phosphatidylethanolamine incorporation into phosphatidylcholine was inhibited in cells exposed to glucagon. Insulin and glucagon had little or no effect on [Me-3H]choline uptake by the hepatocytes. No changes in the activities of the phosphatidylcholine biosynthetic enzymes in cytosol and microsomes from glucagon-treated cells could be detected.