Decreased phosphofructokinase activity in skeletal muscle of diabetic rats.

The activities of phosphofructokinase, aldolase and pyruvate kinase were diminished in extracts from skeletal muscle of streptozotocin diabetic rats, whereas the activities of glucose phosphate isomerase and phosphoglucomutase were not changed. Treatment of diabetic rats with insulin restored the activity of phosphofructokinase to normal. A kinetic study of the partially purified enzyme from normal and diabetic rats showed identical Michaelis constants for ATP and equal sensitivity to inhibition by excess of this substrate. Extracts of quick frozen muscle from diabetic rats had higher levels of citrate (an inhibitor of phosphofructokinase) and lower levels of D-fructose-1,6-bisphosphate and D-glucose-1,6-bisphosphate (activators of this enzyme). The levels of D-fructose-6-phosphate, D-glucose-6-phosphate, ATP, ADP and AMP were the same for the two groups. Our data suggest that the in vivo decrease of phosphofructokinase activity in skeletal muscle of diabetic rats is due to a decrease in the level of the enzymatically active protein as well as to an unfavorable change in the level of several of its allosteric modulators.