Bonadonna R C, del Prato S, Bonora E, Gulli G, Solini A, DeFronzo R A
Metabolism Unit, Consiglio Nazionale delle Ricerche Institute of Clinical Physiology, Pisa, Italy.
Am J Physiol. 1993 Dec;265(6 Pt 1):E943-53. doi: 10.1152/ajpendo.1993.265.6.E943.
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 (approximately 70 microU/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 (approximately 70 microU/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 x kg-1 of lean body mass (LBM), respectively, P < 0.01] and incompletely suppressed (approximately 87%) hepatic glucose production. The major component of nonoxidative glycolysis shifted from glucose recycling in the postabsorptive state (approximately 57% of nonoxidative glycolysis) to glucose conversion to fat during hyperinsulinemia (approximately 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.
通过在输注[3 - 3H] - 和[U - 14C]葡萄糖期间测量3H2O和14CO2的生成速率来评估血浆葡萄糖糖酵解和氧化通量的方法，在健康受试者中进行了测试。在研究1中，对6名受试者进行阶梯式3H2O输注时，计算出的3H2O出现速率与3H2O输注速率密切相符。在研究2中，对4名处于基础状态以及在4小时正常血糖胰岛素（约70微单位/毫升）钳夹期间的受试者输注[2 - 3H]葡萄糖和NaH14CO3，准确获得了[2 - 3H]葡萄糖脱氚速率的估计值（为预期值的94 - 97%），并且在高胰岛素血症期间NaH14CO3的回收系数未改变。在研究3中，11名受试者接受了4小时正常血糖胰岛素（约70微单位/毫升）钳夹，同时输注[3 - 3H] - 和[U - 14C]葡萄糖，并通过间接测热法测量气体交换，以估计总糖酵解、糖原合成、葡萄糖氧化、非氧化糖酵解、肝葡萄糖生成、葡萄糖再循环以及葡萄糖转化为脂肪的速率。高胰岛素血症刺激糖原合成比糖酵解超过基线水平更多[分别为4.78±0.37与2.0±0.17毫克·分钟-1·千克-1瘦体重（LBM），P<0.01]，并且不完全抑制（约87%）肝葡萄糖生成。非氧化糖酵解的主要成分从吸收后状态的葡萄糖再循环（约占非氧化糖酵解的57%）转变为高胰岛素血症期间的葡萄糖转化为脂肪（约占非氧化糖酵解的59%）。胰岛素钳夹期间的脂质氧化与同位素葡萄糖氧化（r = -0.822，P<0.002）和糖酵解（r = -0.582，P<0.07）均呈负相关。总之，在健康受试者中，糖原合成在决定胰岛素介导的葡萄糖处置中比糖酵解和葡萄糖氧化起更大作用。胰岛素介导的糖酵解/氧化增加的部分原因可能是脂肪与葡萄糖氧化竞争缓解的继发结果。
