Effects of physiological hyperinsulinemia on the intracellular metabolic partition of plasma glucose

R. C. Bonadonna, S. Del Prato, E. Bonora, G. Gulli, A. Solini, R. A. DeFronzo

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23 Scopus citations

Abstract

Methodology for assessing the glycolytic and oxidative fluxes from plasma glucose, by measuring 3H2O and 14CO2 rates of production during [3- 3H]- and [U-14C]glucose infusion, was tested in healthy subjects. In study 1, during staircase 3H2O infusion in six subjects, calculated rates of 3H2O appearance agreed closely with 3H2O infusion rates. In study 2, when [2-3H]glucose and NaH14CO3 were infused in four subjects in the basal state and during a 4-h euglycemic insulin (~70 μU/ml) clamp, accurate estimates of the rates of [2-3H]glucose detritiation were obtained (94-97% of the expected values), and the recovery factor of NaH14CO3 did not change during hyperinsulinemia. In study 3, 11 subjects underwent a 4-h euglycemic insulin (~70 μU/ml) clamp with [3-3H]- and [U-14C]glucose infusion and measurement of gaseous exchanges by indirect calorimetry to estimate the rates of total glycolysis, glycogen synthesis, glucose oxidation, nonoxidative glycolysis, hepatic glucose production, glucose recycling, and glucose conversion to fat. Hyperinsulinemia stimulated glycogen synthesis above baseline more than glycolysis [increment of 4.78 ± 0.37 vs. 2.0 ± 0.17 mg · min-1 · kg-1 of lean body mass (LBM), respectively, P < 0.01] and incompletely suppressed (~87%) hepatic glucose production. The major component of nonoxidative glycolysis shifted from glucose recycling in the postabsorptive state (~57% of nonoxidative glycolysis) to glucose conversion to fat during hyperinsulinemia (~59% of nonoxidative glycolysis). Lipid oxidation during the insulin clamp was negatively correlated with both isotopic glucose oxidation (r = -0.822, P < 0.002) and glycolysis (r = -0.582, P < 0.07). In conclusion, in healthy subjects, glycogen synthesis plays a greater role than glycolysis and glucose oxidation in determining insulin-mediated glucose disposal. Part of insulin- mediated increase in glycolysis/oxidation might be secondary to the relief of the competition between fat and glucose for oxidation.

Original languageEnglish (US)
Pages (from-to)E943-E953
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume265
Issue number6 28-6
DOIs
StatePublished - 1993
Externally publishedYes

Keywords

  • glycolysis
  • insulin
  • substrate competition

ASJC Scopus subject areas

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

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