Insulin activates 6-phosphofructo-2-kinase and pyruvate kinase in the liver. Indirect evidence for an action via a phosphatase.
The effect of insulin on hepatic glucose production has been studied in anesthetized rats in the postabsorptive state. Insulin decreases significantly hepatic glucose production within 5-10 min. It also increases the level of fructose 2,6-bisphosphate, via an increase in the Vmax of 6-phosphofructo-2-kinase and concomitantly decreased the activity of fructose-2,6-bisphosphatase, resulting in a 5-fold increase in the ratio of kinase/phosphatase. Insulin also increased the apparent Kd of pyruvate kinase for phosphoenolpyruvate. The changes in the activity of 6-phosphofructo-2-kinase and pyruvate kinase were measured after separation from possible modulators, and suggest a decrease in their phosphorylation state which cannot be attributed to a decrease in the level of cAMP or in the activity of cAMP-dependent protein kinase since these two parameters were not modified by insulin. In addition, neither the activity of phosphorylase a nor that of glycogen synthase were modified. The data strongly suggest that the increase in the glycolytic rate plays a role in the effect of insulin on hepatic glucose production and that insulin mediates its effect on the activity of these enzymes via one or more phosphatases.
Assimacopoulos-Jeannet
F
F
Laboratoires de Recherches Métaboliques, Faculty of Medicine, University of Geneva, Switzerland.
Jeanrenaud
B
B
D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D010762:Phosphorylase a; D006006:Glycogen Synthase; D010770:Phosphotransferases; D011494:Protein Kinases; D025481:Phosphofructokinase-2; D011770:Pyruvate Kinase; D010744:Phosphoric Monoester Hydrolases; D005947:Glucose; D000409:Alanine