Regulation of fructose 2,6-bisphosphate metabolism in human fibroblasts

In the present work, the mechanism involved in the regulation of fructose 2,6-bisphosphate (fructose-2,6-P2) metabolism in human fibroblasts has been studied. Various agents like serum, insulin and adrenaline known to affect glycolysis have been investigated for their ability to influence fructose 2,6-P2 metabolism in confluent human fibroblasts. Serum appears to be the most potent activator of fructose-2,6-P2 levels and capable of inducing a marked increase in 6-phosphofructo-2-kinase (ATP: D-fructose-6-phosphate-2-phosphotransferase), EC 2.7.1. 105). To a lesser extent insulin has the same effects. The increase in enzyme activity elicited by serum and insulin does not require de novo protein synthesis since the process is insensitive to cycloheximide. Incubation of fibroblasts in the presence of adrenaline is responsible for a significant rise in fructose-2,6-P2 levels without affecting 6-phosphofructo-2-kinase. Similar experiments performed on glucose-starved or cytochalasin B-treated cells show that the effects elicited by all the agents are strictly dependent on glucose availability.