QUANTITATION OF GLYCOLYSIS AND SKELETAL-MUSCLE GLYCOGEN-SYNTHESIS IN HUMANS

We measured the net rates of skeletal muscle glycogen synthesis and gl ycolysis (conversion of [3-H-3]glucose to (H2O)-H-3) in healthy overni ght-fasted volunteers. Two studies were performed. In study 1, seven s ubjects participated in two paired infusions under basal conditions of either [2-H-3]glucose (H2) or [3-H-3]glucose (H3). Total glucose upta ke (R(d)) and rates of whole body (H2O)-H-3 formation ((H2O)-H-3 R(a)) were measured. With H2, R(d) and (H2O)-H-3 R(a) were similar. With H3 , (H2O)-H-3 R(a), equal to glycolysis, was 65% of R(d). In study 2, si x different subjects underwent a 3-h, 40 mU.m-2.min-1 euglycemic insul in clamp. [6,6-H-2(2)]glucose was infused throughout and H3 was infuse d during the last hour of the study. Open muscle biopsies were obtaine d at 150 and 180 min. Glycogen synthesis was assessed by three indepen dent means: 1) direct measurement, as H-3 disintegrations per minute i n isolated muscle glycogen per plasma H3 specific activity; 2) extrapo lation from the activity of glycogen synthase assayed in the presence of the concentrations of glucose 6-phosphate and UDP-glucose measured in the biopsy; and 3) the difference between Rd and glycolysis. Despit e a wide range in R(d) [24.5-58.8 mumol . kg fat-free mass (FFM)-1.min -1] and glycolysis (14.2-26.1), the three methods yielded similar resu lts of 20.0 +/- 3.9, 22.5 +/- 3.7, and 20.6 +/- 3.7 mumol.kg FFM-1.min -1 and correlated highly with each other (r2 = 0.92-0.96). Our results (study 1) indicate that the rate of plasma tritiated water formation reflects the intracellular detritiation of tritiated glucose. Under hy perinsulinemic conditions (study 2) the net rate of muscle glycogen sy nthesis can be accurately estimated from the glycogen synthase activit y and from the difference between total glucose uptake and glycolysis. Thus, at high physiological plasma insulin concentrations resulting i n submaximAl stimulation of muscle glycogen synthesis, the latter can be accurately measured in humans.