FIGURE 9.

Model. The insulin/IGF-1 signaling pathway (purple) results in translocation of GLUT4 vesicles to the PM, facilitating increased glucose uptake. Glucose can either be converted to lactate (aerobic glycolysis, green) or undergo oxidative phosphorylation in the mitochondria (red). PFKFB3 generates Fru-2,6-BP (F2,6BP), a potent activator of PFK-1 and thus glycolysis. The insulin/IGF-1 signaling pathway positively regulates glucose uptake and glucose metabolism (purple arrow) and our data show that partitioning of glucose toward aerobic glycolysis potentiates insulin signaling (green arrow), whereas we predict that this effect will either not be seen or even inhibited when glucose undergoes mitochondrial oxidative phosphorylation. Drugs/inhibitors used in the study and their targets are indicated. G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; F1,6BP, fructose 1,6-bisphosphate.