Time course of skeletal muscle glucose uptake during euglycemic hyperinsulinemia in the anesthetized rabbit: a...

Since skeletal muscle has been implicated as the major site of insulin resistance, the purpose of this study was to examine in detail the time course of muscle glucose uptake during the onset and maintenance of euglycemic hyperinsulinemia. Uptake of 18F-2-deoxy-2-fluoro-D-glucose (FDG) by the thigh muscle of an anesthetized rabbit was monitored by a single pair of coincidence photon detectors. Graphical analysis of tissue and plasma radioactivity concentrations was performed to derive fractional rates of FDG phosphorylation continuously. FDG phosphorylation rates were determined during rest (glucose 7 mM, insulin 5-10 microU/ml) and subsequent 5-min intervals under conditions of euglycemic hyperinsulinemia (glucose 6-8 mM; insulin 350-400 microU/ml plasma). FDG phosphorylation did not increase above resting control levels until 5.5 +/- 1.5 min after intravenous insulin administration. After 20-30 min of hyperinsulinemia, FDG phosphorylation and calculated glucose metabolic rates were increased by 50%. At 35-40 min of the clamp in place, there was a second increase in tracer phosphorylation which plateaued at 200% of control (p less than 0.01) and remained at this level for the remainder of the experiment. In conclusion, we have described a method for making rapid, serial estimates of insulin-mediated skeletal muscle glucose uptake. We suggest that appraisal of the time course of glucose uptake with FDG will aid in the understanding of normal and pathophysiologic states of insulin action in vivo.