Quantitation of glycolysis and skeletal muscle glycogen synthesis in humans

L. Rossetti, Y. T. Lee, J. Ruiz, S. C. Aldridge, H. Shamoon, G. Boden

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

We measured the net rates of skeletal muscle glycogen synthesis and glycolysis (conversion of [3-3H]glucose to 3H2O) in healthy overnight- fasted volunteers. Two studies were performed. In study 1, seven subjects participated in two paired infusions under basal conditions of either [2- 3H]glucose (H2) or [3-3H]glucose (H3). Total glucose uptake (R(d)) and rates of whole body 3H2O formation (3H2O R(a)) were measured. With H2, R(d) and 3H2O R(a) were similar. With H3, 3H2O R(a), equal to glycolysis, was 65% of R(d). In study 2, six different subjects underwent a 3-h, 40 mU · m-2 · min-1 euglycemic insulin clamp. [6,6-2H2]glucose was infused throughout and H3 was infused during the last hour of the study. Open muscle biopsies were obtained at 150 and 180 min. Glycogen synthesis was assessed by three independent means: 1) direct measurement, as 3H disintegrations per minute in isolated muscle glycogen per plasma H3 specific activity; 2) extrapolation 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 R(d) and glycolysis. Despite a wide range in R(d) [24.5-58.8 μmol · kg fat-free mass (FFM)-1 · min-1] and glycolysis (14.2-26.1), the three methods yielded similar results of 20.0 ± 3.9, 22.5 ± 3.7, and 20.6 ± 3.7 μmol · 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 hyperinsulinemic conditions (study 2) the net rate of muscle glycogen synthesis can be accurately estimated from the glycogen synthase activity and from the difference between total glucose uptake and glycolysis. Thus, at high physiological plasma insulin concentrations resulting in submaximal stimulation of muscle glycogen synthesis, the latter can be accurately measured in humans.

Original languageEnglish (US)
Pages (from-to)E761-E769
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume265
Issue number5 28-5
DOIs
StatePublished - 1993

Keywords

  • glucose uptake
  • insulin action

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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