Effects of adrenalectomy on hormone action on hepatic glucose metabolism. Impaired glucagon activation of glycogen phosphorylase in hepatocytes from adrenalectomized rats

• Published in: The Journal of biological chemistry 1979-11, Vol.254 (22), p.11374-11378
• Main Authors: Chan, T M, Steiner, K E, Exton, J H
• Format: Article
• Language: English
• Subjects: Adrenalectomy; Animals; Cyclic AMP - metabolism; Cyclic AMP - pharmacology; Enzyme Activation - drug effects; Glucagon - pharmacology; Glucose - metabolism; In Vitro Techniques; Liver - drug effects; Liver - metabolism; Male; Phosphorylase b - metabolism; Phosphorylase Kinase - metabolism; Phosphorylases; Protein Kinases - metabolism; Rats
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)86496-7

The effects of adrenalectomy on glucagon activation of liver glycogen phosphorylase and glycogenolysis were studied in isolated hepatocytes. Adrenalectomy resulted in reduced responsiveness of glycogenolysis and phosphorylase to glucagon activation. Stimulation of cAMP accumulation and cAMP-dependent protein kinase activity by glucagon was unaltered in cells from adrenalectomized rats. Adrenalectomy did not alter the proportion of type I and type II protein kinase isozymes in liver, whereas this was changed by fasting. Activation of phosphorylase kinase by glucagon was reduced in hepatocytes from adrenalectomized rats, although the half-maximal effective concentration of glucagon was unchanged. No difference in phosphorylase phosphatase activity between liver cells from control and adrenalectomized rats was detected. Glucagon-activated phosphorylase declined rapidly in hepatocytes from adrenalectomized rats, whereas the time course of cAMP increase in response to glucagon was normal. Addition of glucose (15 mM) rapidly inactivated glucagon-stimulated phosphorylase in both adrenalectomized and control rat hepatocytes. The inactivation by glucose was reversed by increasing glucagon concentration in cells from control rats, but was accelerated in cells from adrenalectomized rats. It is concluded that impaired activation of phosphorylase kinase contributes to the reduced glucagon stimulation of hepatic glycogenolysis in adrenalectomized rats. The possible role of changes in phosphorylase phosphatase is discussed.