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

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Abstract
The current study examined in vivo insulin regulation of glucose transport and phosphorylation in skeletal muscle of healthy, lean volunteers. Positron 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-[18F]fluoro-d-glucose ([18F]FDG) was performed during metabolic steady-state conditions at four rates of euglycemic insulin infusion. Leg glucose uptake (LGU) was determined by arteriovenous limb balance assessments. The metabolism of [18F]FDG strongly correlated with skeletal muscle LGU ( r= 0.72, P < 0.01). On the basis of compartmental modeling, the fraction of glucose undergoing phosphorylation (PF) increased in a dose-responsive manner from 11% during basal conditions to 74% at the highest insulin infusion 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 nonphosphorylated [18F]FDG ( P < 0.05). In step-wise regression analysis, the volume of distribution of nonphosphorylated [18F]FDG and the rate constant for glucose phosphorylation accounted for most of the variance in LGU ( r = 0.91, P < 0.001). These findings indicate an important interaction between transport and phosphorylation in the control of insulin-stimulated glucose metabolism in skeletal muscle.