Glucose In Human Skeletal Muscle Research Articles

Glucose phosphorylation is/is not a significant barrier to muscle glucose uptake by the working muscle

The following letters are in response to the Point:Counterpoint series “Glucose phosphorylation is/is not a significant barrier to muscle glucose uptake by the working muscle” that appears in this issue. To the Editor : The Point:Counterpoint debate ([4][1], [6][2]) provides important insights

Evidence for 100% 13C NMR visibility of glucose in human skeletal muscle.

The accuracy of the measurement of total muscle glucose by in vivo 13C NMR spectroscopy was tested in five normal volunteers during a euglycemic [1-13C]glucose infusion. The NMR visible concentration calibrated using an external reference was compared with that calculated from plasma glucose concentration, assuming that glucose remained extracellular. The NMR measurement always provided higher values than the calculation from plasma glucose: 0.51 +/- 0.035 (mean +/- SE) versus 0.38 +/- 0.005 mmol/liter of muscle on average. This systematic difference was interpreted as reflecting the presence of muscle glucose-6-phosphate, co-resonating with free glucose. Thus, glucose appeared to be virtually 100% NMR visible in human skeletal muscle.

Key metabolite kinetics in human skeletal muscle during ischaemia and reperfusion: measurement by microdialysis.

The tissue kinetics of key metabolites of ischaemic and postischaemic tissue damage were studied in the intercellular space of human skeletal muscle by microdialysis. In vivo microdialysis calibration experiments (n = 5) yielded the basal intercellular concentration of glucose in human skeletal muscle (3.6 +/- 0.6 mM; mean +/- SD). The corresponding mean plasma glucose concentration was 4.3 +/- 0.2 mM which was significantly higher. The time vs. concentration profiles of intercellular glucose (n = 7), lactate (n = 5), TxB2 (n = 6) and urea (n = 8) were characterized during a 20 min period of leg constriction. TxB2 increased exclusively during reperfusion in comparison to baseline (n = 6). Administration of 500 mg acetylsalicylic acid, 5-10 min after onset of ischaemia blunted TxB2-response to reperfusion (n = 4). It is concluded that intercellular muscle glucose concentration is less than that in plasma. Glucose uptake in skeletal muscle is rapid even under ischaemic conditions. Synthesis and release of TxB2 is not evident during ischaemia. TxB2 mediated reperfusion injury might be reduced by acetylsalicylic acid, even if administered after onset of ischaemia.

Hyperglycemia induces accumulation of glucose in human skeletal muscle

The effect of hyperglycemia on whole body substrate utilization and the metabolic profile of skeletal muscle has been investigated. Eight glucose-tolerant men were infused with somatostatin (S) for 190 min. During the last 120 min of S infusion, glucose was infused to achieve a steady-state plasma level of 26 mmol/l. Biopsies were obtained from the quadriceps femoris muscle immediately before and 35 and 120 min after induction of hyperglycemia. Steady-state glucose disposal during hyperglycemia averaged (+/- SE) 33.8 +/- 3.2 mumol.kg fat-free mass-1.min-1, and approximately 70% of the glucose disposal was accounted for by skeletal muscle. Intracellular glucose increased from 0.9 +/- 0.2 mmol/kg dry wt during S to 9.5 +/- 2.5 during hyperglycemia (P less than 0.01). It was estimated that approximately 35% of the glucose taken up by muscle during 120 min of hyperglycemia was not phosphorylated. Muscle contents of alpha-D-glucose 1,6-diphosphate, D-glucose 6-phosphate, ATP, ADP, and AMP (both of which are based on the phosphocreatine-to-creatine ratio), which have been shown to inhibit hexokinase in vitro, did not change significantly during hyperglycemia, nor were there any significant changes in any of the other postphosphofructokinase intermediates, D-fructose 2,6-diphosphate, and citrate. Hyperglycemia did not alter the fractional activities of glycogen synthase or phosphorylase, nor total phosphorylase activity. However, hyperglycemia resulted in a 55% increase in glycogen synthase-specific activity (P less than 0.01). It is concluded that hyperglycemia results in a marked increase in muscle glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

No accumulation of glucose in human skeletal muscle during euglycemic hyperinsulinemia.

It has been recently suggested that high glucose infusion rates during euglycemic hyperinsulinemia result in accumulation of free glucose in human skeletal muscle (J. Clin. Invest. 76: 357, 1985). To examine this possibility, we performed a euglycemic, hyperinsulinemic clamp together with biopsies from the quadriceps femoris muscle on seven healthy men. Insulin was infused at successive rates of 40 and 400 mU. m-2.min-1, resulting in mean plasma insulin concentrations of 69 +/- 3 and 1,285 +/- 115 (SE) microU/ml, respectively. Glucose infusion rates averaged 7.79 +/- 0.86 and 12.01 +/- 0.77 mg.kg body wt-1.min-1. The total glucose content in muscle averaged 1.72 +/- 0.26, 1.37 +/- 0.21, and 1.65 +/- 0.35 mmol/kg dry wt at rest, and after the low- and high-dose insulin infusions, respectively (P greater than 0.05). Assuming that the plasma glucose concentration reflects the glucose concentration in the extracellular space and that there are 0.3 liters of extracellular water per kilogram dry weight, the intracellular glucose contents are calculated to be 0.15 +/- 0.25, -0.35 +/- 0.21, and -0.06 +/- 0.34 mmol/kg dry wt at rest, and after the low- and high-dose infusions, respectively. None of these values is significantly different from zero. Thus euglycemic hyperinsulinemia does not result in appreciable accumulation of glucose in the muscle of insulin-sensitive men.