Chemical mediator of insulin action stimulates lipid synthesis and down regulates the insulin receptors in primary cultures of rat hepatocytes

Incubation of rat liver particulate fraction with insulin causes the release of a substance that stimulates lipid synthesis and down regulates the insulin receptor in primary cultures of isolated rat hepatocytes. This substance may be similar to putative mediator(s) of insulin action which has been shown to modulate the activity of key enzymes of lipid and carbohydrate metabolism in various cell free systems. Our data demonstrate that the mediator of insulin is also biologically active in an intact cell system. Down regulation of the insulin receptor by the mediator supports the concept that this phenomenon is a post binding event of insulin action.