Quantification of glucose transport and phosphorylation in human skeletal muscle using FDG PET

PET with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is used for quantifying gl ucose metabolism in brain and myocardium in vivo. We developed and validate d a similar procedure for the quantification of the two initial steps of gl ucose metabolism in skeletal muscle in vivo. Methods: The measurement proto col was first optimized by computer simulations. In addition to the accurac y in sampling plasma input and tissue time-activity curves, precise determi nation of the fractional blood volume, that is, the extracellular tissue vo lume fraction, plays a key role in correctness of the determined model cons tants. The optimized protocol was subsequently used to estimate transmembra ne muscular glucose transport and hexokinase activity in six human subjects with normal or altered glucose utilization. PET was performed during the s teady state of an euglycemic hyperinsulinemic clamp. Results: A three-compa rtment model provides a better description of the experimental data than a two- or four-compartment model. Glucose clearance from the extracellular co mpartment into the skeletal muscle cell (K-1) ranges from 0.024 to 0.093 mL /g/min. The intracellular glucose phosphorylation rate (k(3)) varies betwee n 0.030 and 0.142 min(-1). The regional muscular glucose utilization, as ca lculated from the determined model parameters, lies between 10.7 and 83.3 m u mol/kg/min and correlates with the whole-body glucose utilization as inde pendently determined (R-2 = 0.83; P less than or equal to 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 skele tal muscle. An optimized measurement protocol is developed and applied to e xperimental data. This experimental approach should be appropriate to test whether glucose transport or hexokinase activity is altered in disorders of muscular glucose utilization.