REGULATION OF GLUCOSE-UPTAKE AND METABOLISM BY WORKING MUSCLE - AN INVIVO ANALYSIS

To assess the mechanisms whereby muscular work stimulates glucose upta ke and metabolism in vivo, dogs were studied during rest (-40-0 min), moderate exercise (0-90 min), and exercise recovery (90-180 min) with plasma glucose clamped at 5.0, 6.7, 8.3, and 10.0 mM (n = 5 at 5.0 mM and n = 4 at all other levels) using a variable glucose infusion. Basa l insulin was maintained with somatostatin and insulin replacement. Wh ole-body glucose uptake, limb glucose uptake, and oxidative and nonoxi dative glucose plus lactate metabolism, were assessed with tracers ([H -3]glucose and [C-14]glucose) and arteriovenous differences. The combi ned effects of glucose and exercise on the increment above resting val ues for limb glucose uptake, arteriovenous glucose difference, LGO, LG NO, and rate of glucose disappearance were synergistic (approximately 1 12, 90, 125, 76, and 90% greater than the additive values, respectiv ely). Neither exercise nor recovery affected the K(m) for limb glucose uptake (4.7 +/- 1.1, 4.8 +/- 0.4, and 5.2 +/- 0.3 mM during rest, exe rcise, and recovery, respectively), but both conditions increased the V(max) (44 +/- 16, 217 +/- 30, and 11 8 +/- 14 mumol/min during rest, exercise, and recovery, respectively). Similarly, the K(m) for arterio venous glucose differences were unaffected by exercise recovery (4.9 /- 0.6, 5.0 +/- 0.4, and 5.3 +/- 0.3 mM during rest, exercise, and rec overy, respectively), but the maximum rose (272 +/- 50, 650 +/- 78, an d 822 +/- 111 muM during rest, exercise, and recovery, respectively). The LGO was unchanged by glycemia at rest (15 +/- 4 mumol/min at 10.0 mM). The K(m) for LGO during exercise was 5.1 +/- 0.3 mM, and the V(ma x) was 163 +/- 15. The capacity for LGO returned to basal during recov ery. LGNO increased gradually with increasing glycemia during rest, ex ercise, and recovery and did not approach saturation (38 +/- 13, 105 /- 36, and 132 +/- 45 mumol/min during rest, exercise, and recovery, r espectively, at 10.0 mM). In general, the LGNO was elevated at every g lucose level during exercise (approximately twofold) and recovery (app roximately threefold) compared with rest. Arterial free fatty acid and glycerol levels decreased with increasing glycemia within all periods . Free fatty acids were suppressed by a greater amount during exercise compared with rest and recovery. This study shows that 1) the combine d effects of exercise and increased glucose level act synergistically on glucose uptake and metabolism; 2) exercise increases the V(max) for limb glucose uptake and arteriovenous glucose difference without alte ring the K(m) for these variables; 3) the capacity for LGNO predominat es at rest, whereas the capacity for LGO predominates during exercise; 4) during recovery the capacity for LGO returned to basal, whereas th at for LGNO remained elevated; and 5) glucose-induced suppression of f ree fatty acid levels was greatest during exercise. In conclusion, an increase in circulating glucose within the physiological range, which has only minor effects at rest, profoundly increases muscle glucose me tabolism and decreases free fatty acid availability during exercise.