Short-term regulation of glucokinase.

The activity of liver glucokinase is controlled in the short term by the concentration of its substrate glucose and by a regulatory protein, which acts as a competitive inhibitor with respect to glucose. In mammalian species, the effect of this protein is modulated by fructose 6-phosphate, which reinforces the inhibition, and by fructose 1-phosphate which antagonizes it. In the rat, the regulatory protein is found in the two tissues that express glucokinase, i.e., the liver and the pancreatic islets. Of particular interest is the fact that the regulatory protein is absent from the liver in those species that have no hepatic glucokinase. These results indicate that the two proteins form a functional unit. The regulatory protein appears in rat liver before birth, whereas glucokinase is only synthesized after 15 days of extrauterine life. The concentration of regulatory protein in the liver of the adult rat decreases by about 50% during starvation and in diabetes mellitus. Under these conditions, the difference between the concentrations of regulatory protein and glucokinase remains constant at about 0.4-0.5 nmol/g.