Insulin regulation of glucose transport and phosphorylation in skeletal muscle assessed by PET

The current study examined in vivo insulin regulation of glucose transport and phosphorylation in skeletal muscle of healthy, lean volunteers. Positro n emission tomography (PET) imaging and compartmental modeling of the time course of skeletal muscle uptake and utilization after a bolus injection of 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) was performed during metaboli c steady-state conditions at four rates of euglycemic insulin infusion. Leg glucose uptake (LGU) was determined by arteriovenous limb balance assessme nts. The metabolism of [F-18]FDG strongly correlated with skeletal muscle L GU (r = 0.72, P < 0.01). On the basis of compartmental modeling, the fracti on of glucose undergoing phosphorylation (PF) increased in a dose-responsiv e manner from 11% during basal conditions to 74% at the highest insulin inf usion rate (P < 0.001). The PF and LGU were highly correlated (r = 0.73, P < 0.001). Insulin also increased the volume of distribution of nonphosphory lated [F-18]FDG (P < 0.05). In step-wise regression analysis, the volume of distribution of nonphosphorylated [F-18]FDG and the rate constant for gluc ose phosphorylation accounted for most of the variance in LGU (r = 0.91, P < 0.001). These findings indicate an important interaction between transpor t and phosphorylation in the control of insulin-stimulated glucose metaboli sm in skeletal muscle.