Hormonal effects on cyclic nucleotides and carbohydrate and lipid metabolism in isolated chicken hepatocytes

Abstract The basal cAMP content of isolated chicken hepatocytes (0.5–1.5 pmol 10 6 cells) was increased transitorily by both glucagon (up to 60-fold) and adrenaline (up to 20-fold). These hormones stimulated cellular glycogenolysis by up to 200% and gluconeogenesis from lactate by up to 30%, and inhibited lipogenesis from acetate by up to 90%. Half-maximal metabolic effects were induced by hormone concentrations that were less than 10% of the concentrations producing a half-maximal rise in cAMP. Physiological concentrations of insulin and avian pancreatic polypeptide (APP) failed to alter basal or hormone-elevated cAMP concentrations, and were also without effect on glycogenolysis, gluconeogenesis, and lipogenesis. Insulin failed to stimulate glycogen synthesis. None of these hormones affected the cGMP content of the hepatocytes (0.03 pmol/10 6 cells), or altered hepatocyte phosphodiesterase activity. Since high-affinity insulin receptors are present on these chicken hepatocytes we conclude that the insulin resistance of chickens in vivo is due to lack of a hormone effector system in the liver; the lack of metabolic effects resulting from APP is consistent with its lack of receptors on the hepatocytes.