J. Biochem, 1984, Vol. 95, No. 6 1691-1696
© 1984 Japanese Biochemical Society
research-article |
Glucagon and Glucose as Major Regulators of Glycogen Metabolism in Primary Cultured Rat Hepatocytes1
Institute for Enzyme Research, School of Medicine, University of Tokushima Tokushima, Tokushima 770
The short-term controls of glycogen synthase [EC 2.4.1.11
[EC]
] and glycogen phosphorylase [EC 2.4.1.1
[EC]
] by major regulators, such as insulin, glucose, catecholamine, and glucagon, were compared in a simple, yet organized experimental system, i.e., adult rat hepatocytes in primary culture. Glycogen synthase was activated by glucose markedly and dose-dependently (540 mM), but insulin alone (1 x 108 M) activated this enzyme only two-fold. Therefore, activation of the enzyme by the two regulators together was mostly due to activation by glucose. Glucagon at a concentration of 5 x 1010 M suppressed this activation almost completely. Glucagon at this concentration activated phosphorylase considerably and this activation was slightly inhibited by insulin. Phenylephrine also activated phosphorylase, and this activation was inhibited by phenoxybenzamine or prazosin, suggesting that activation by catecholamine is through the
1-adrenergic receptor. Similarly a high concentration of glucose diminished the effects of glucagon and phenylephrine. These results suggest that in rat liver, glycogen metabolism is controlled mainly by glucagon, catecholamine, and glucose; the former two activate phosphorylase and inactivate synthase, while glucose activates synthase strongly and inactivates phosphorylase partially. Insulin plays a minor role in both reactions. Thus, the liver is primarily an organ for glucose production, which is regulated by hormones, not for glycogen storage, which is increased only by a high glucose concentration in the portal blood.
1This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.
2Present address: Research Laboratories, Otsuka Pharmaceutical Co., Ltd., Kawauchi, Tokushima, Tokushima 771-01.