Upregulation of heart PFK-2/FBPase-2 isozyme in skeletal muscle after persistent contraction.

Fructose-2,6-bisphosphate (Fru-2,6-P(2)) is the most potent allosteric activator of liver 6-phosphofructo-1-kinase enzyme, which is crucial for glycolysis. It is present in skeletal muscle but its importance is controversial as a regulator of muscle glycolysis. This study aims to determine the role of Fru-2,6-P(2) in the control of muscle glycolysis during contraction. Muscle contraction was produced by chronic low-frequency stimulation of rabbit tibialis anterior for 24 h, followed by a rest period of 48 h. To determine muscle glycolysis adaptation, we applied a short functional electrostimulation test using the same system of low-frequency stimulation for 1, 3, and 10 s. The variation in concentration of lactate and pyruvate was used to calculate the flux along the glycolysis pathway and the Fru-1,6-P(2)/Fru-6-P ratio permitted to analyze the 6-phosphofructo-1-kinase activation. Fru-2,6-P(2) levels increased over the 24 h of stimulation and remained elevated after the rest period, this being the only metabolite that kept the changes produced by chronic low-frequency stimulation during the rest. During the short functional electrostimulation test, the glycolytic pathway in stimulated and rested muscle was more active than in control muscle, which coincided with higher kinase activity of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) enzyme. Furthermore, we found a decrease in muscle, liver, and ubiquitous PFK-2/FBPase-2 isoform expression and an increase in heart isoform expression. For the first time, we demonstrate that a persistent increase in Fru-2,6-P(2) produced by a change in PFK-2/FBPase-2 isoform expression may play an important role in the regulation of muscle glycolysis during the first moments of exercise.