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Quantification of Glucose Transport and Phosphorylation in Human Skeletal Muscle Using FDG PET

Department of Nuclear Medicine, Heinrich-Heine-University, Düsseldorf
Forschungszentrum Juelich
Diabetes Research Institute, Düsseldorf, Germany

Correspondence: For correspondence or reprints contact: Martin Reinhardt, MD, Department of Nuclear Medicine, Heinrich-Heine-University, Moorenstr. 5, D-40225 Düsseldorf, Germany.

ABSTRACT

PET with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) is used for quantifying glucose metabolism in brain and myocardium in vivo. We developed and validated a similar procedure for the quantification of the two initial steps of glucose metabolism in skeletal muscle in vivo. Methods: The measurement protocol was first optimized by computer simulations. In addition to the accuracy in sampling plasma input and tissue time-activity curves, precise determination of the fractional blood volume, that is, the extracellular tissue volume fraction, plays a key role in correctness of the determined model constants. The optimized protocol was subsequently used to estimate transmembrane muscular glucose transport and hexokinase activity in six human subjects with normal or altered glucose utilization. PET was performed during the steady state of an euglycemic hyperinsulinemic clamp. Results: A three-compartment model provides a better description of the experimental data than a two- or four-compartment model. Glucose clearance from the extracellular compartment into the skeletal muscle cell (K₁) ranges from 0.024 to 0.093 mL/g/min. The intracellular glucose phosphorylation rate (k₃) varies between 0.030 and 0.142 min^-1. The regional muscular glucose utilization, as calculated from the determined model parameters, lies between 10.7 and 83.3 µmol/kg/min and correlates with the whole-body glucose utilization as independently determined (R² = 0.83; P <- 0.01). Conclusion: We demonstrate by computer simulations that a three-compartment model can be used to characterize the first two steps of glucose metabolism in skeletal muscle. An optimized measurement protocol is developed and applied to experimental data. This experimental approach should be appropriate to test whether glucose transport or hexokinase activity is altered in disorders of muscular glucose utilization.

Key Words: glucose metabolism • skeletal muscle • FDG PET • hexokinase • glucose transport • PET

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