Intra- and intercellular mechanisms regulating glucose metabolism in the liver.

The regulation of glucose metabolism in the liver by intraand intercellular mechanisms was studied. Fructose-1,6-bisphosphatase, an enzyme involved in de novo synthesis of glucose was found to be stimulated by glucagon in isolated parenchym~l liver cells. Glucagon increased the Vmax of fructo;:;e-1,6-bisphosphatase. This increase could be abolished by gel-filtration of the enzyme, indicating that stimulation of fructose-1, 6-bisphosphatase is caused by an . activator of the enzyme. In human liver, protein phosphorylation was studied in order to extend results from animal studies to the human situation. In the human liver cytosolic fraction three proteins were phosphorylated by cAMP-dependent protein kinase, two proteins by Ca2 +dependent protein kinase(s) and five proteins were phosphorylated by both types of protein kinases. The cAMP-dependent phosphorylation of L-type pyruvate kinase and the cAMP-and Ca2 +-independent phosphorylation of a protein with a molecular weight of 68,000 was inhibited by phosphorylated hexoses. Protein phosphorylation in human liver was found to be similar to that in rat liver.