Determination of muscle-specific glucose flux using radioactive stereoisomers and microdialysis

The purpose of the present study was to evaluate a novel approach for deter mining skeletal muscle-specific glucose flux using radioactive stereoisomer s and the microdialysis technique. Microdialysis probes were inserted into the vastus lateralis muscle of human subjects and perfused (4 mul/min) with a Ringer solution containing small amounts of radioactive D- and L-glucose as the internal reference markers for determining probe recovery as well a s varying concentrations of insulin (0-10 mM). The rationale behind this ap proach was that both stereoisomers would be equally affected by the factors that determine probe recovery, with the exception of L-glucose, which is n onmetabolizable and would not be influenced by tissue uptake. Therefore, an y differences in the probe recovery ratios between the D- and L-stereoisome rs represent changes in skeletal muscle glucose uptake directly at the tiss ue level. There were no differences in probe recovery between the D- (42.3 +/- 3.5%) and L- (41.2 +/- 3.5) stereoisomers during the control period (no insulin), which resulted in a D/L ratio of 1.04 +/- 0.03. However, during insulin perfusion (1 muM). The D/L ratio increased to 1.62 +/- 0.08 and 1.5 8 +/- 0.07 (P < 0.05) during the two collection (0-15 and 15-30 min) period s, respectively. This was accomplished solely by an increase (P < 0.05) in D- glucose probe recovery, as L- glucose probe recovery remained unchanged. In a second set of experiments, the perfusion of 10 muM insulin did not in crease the D/L ratio (1.40 +/- 0.11) above that observed during 1.0 muM (1. 41 +/- 0.07) insulin perfusion. These data suggest that this method is suff iciently sensitive to detect differences in insulin-stimulated glucose upta ke; thus the use of radioactive stereoisomers in conjunction with the micro dialysis technique provides a novel and useful technique for determining ti ssue-specific glucose flux and insulin sensitivity.