Hypothalamic control of liver glycogen metabolism in adult and aged rats

The regulatory function of the hypothalamus in the metabolism of liver glycogen was investigated by analyzing the changes in the activities of the rate-limiting enzymes implicated in glycogen breakdown (glycogen phosphorylase) and synthesis (glycogen synthetase), after electrical stimulation of the ventromedial hypothalamic nucleus (VMH) and the lateral hypothalamic nucleus (LH) of rats. Electrical stimulation of the VMH induced rapid and marked increase in the content of the active form of phosphorylase in the liver, but it did not affect the synthetase. Stimulation of the LH, on the other hand, caused an increase in the level of the active form of synthetase, but produced little change in the phosphorylase activity. The concentration of insulin in the portal blood decreased significantly on stimulation of the VMH, but did not change appreciably on stimulation of the LH. The ability of the hypothalamus to control liver glycogen metabolism was found to be impaired in 2-year-old rats: the magnitude and duration of the early increase in active phosphorylase in response to VMH stimulation were reduced, and the response of synthetase to LH stimulation was slow.The results are discussed from the viewpoint that the VMH and LH are the centers for controlling irect neural and neural-hormonal regulations of liver glycogen metabolism. It is concluded that the VMH-splanchnic nerve pathway is an important neural component for controlling glycogenolysis and glucose output by the liver, and that the LH-vagal pathway is an opposing neural component for controlling glycogenesis in the liver.