Regulation of glycogen metabolism in liver by the autonomic nervous systemV. Activation of glycogen synthetase by vagal stimulation

Results indicate that vagal stimulation results in activation of glycogen synthetase, whereas splanchnic-nerve stimulation causes inactivation of the enzyme, which is closely correlated with the time course of decrease in the UDPG and Glc-6- P levels in the liver.

Abstract

1. Electrical stimulation of the vagus nerve of rabbits caused a marked increase in the activity of liver glycogen synthetase (UDPG:α-1,4-glucan α-4-glucosyltransferase, EC 2.4.1.11). Stimulation of the splanchnic nerve resulted in a decrease in enzymic activity. 2. On vagal stimulation the glycogen synthetase activity increased to nearly the maximal level within 10 min, and its change was closely correlated with the time course of decrease in the UDPG and Glc-6-P levels in the liver. 3. Increase in enzymic activity on vagal stimulation is not due to a change in the total activity of the enzyme, but appears to be due to transformation of the enzyme to a form with higher affinities for UDPG and Glc-6-P. Vagal stimulation for 10 min lowered the apparent Km for UDPG from 2.9 · 10−3 to 4.8 · 10−4 M (determined in the presence of a physiological concentration of Glc-6-P, without causing a significant change in vmax. The apparent Ka for Glc-6-P was also lowered from 7.1 · 10−4 to 2.2 · 10−4 M by vagal stimulation. These effects of vagal stimulation were not affected by removal of the pancreas. 4. Splanchnic-nerve stimulation caused a slight increase in the apparent Km for UDPG of glycogen synthetase, without affecting the value of vmax. 5. These results indicate that vagal stimulation results in activation of glycogen synthetase, whereas splanchnic-nerve stimulation causes inactivation of the enzyme. The possible mechanisms and physiological significance for the actions of these two autonomic nerves on the regulation of glycogen synthetase and glycogen metabolism in the liver are discussed.