Underestimation of Glucose Turnover Measured With [6-3H]- and [6,6-2 H2]- but not [6-14C]glucose During Hyperinsulinemia in Humans
Underestimation of Glucose Turnover Measured With [6-3H]- and [6,6-2 H2]- but not [6-14C]glucose During Hyperinsulinemia in Humans
复制标题
在人类高胰岛素血症期间用 [6-3H]- 和 [6,6-2 H2]- 而不是 [6-14C] 葡萄糖测量的葡萄糖周转率被低估
作者：
M. Mcmahon;W. Schwenk;M. Haymond;R. Rizza
最近的研究表明，氢标记的葡萄糖示踪剂低估了高通量条件下人体内的葡萄糖周转。这种低估的原因尚不清楚。为了确定误差是否为时间依赖性、合并液依赖性、模型依赖性或胰岛素依赖性，在7小时输注胰岛素（1 mU · kg−1 · min−1）或生理盐水期间，同时测量[6- 3 H]-、[6，6 - 2 H2]-和[6- 14 C]葡萄糖的葡萄糖转换率。在胰岛素输注过程中，用[6- 3 H]葡萄糖和葡萄糖浓度测定稳态葡萄糖转换率。（8.0 ± 0.5 mg · kg-1 · min-1）和[6，6- 2 H2]葡萄糖（7.6 ± 0.5 mg kg−1 min−1）较低（P < .01）比维持正常血糖所需的葡萄糖输注速率（9.8 ± 0.6 mg · kg−1 · min−1）或用[6-14 C]葡萄糖测定并校正科里循环活性的葡萄糖周转率（9.8 ± 0.7 mg · kg−1 ·min 1）。因此，用[6-3 H]-或[6，6 -2 H2]-而不是[6-14 C]葡萄糖获得“负”葡萄糖产生率（P <0.01）。用[6-3 H]葡萄糖估计的周转率与实际葡萄糖处置（或14 C葡萄糖通量）之间的差异不随时间减少，也不依赖于同位素输注的持续时间。在生理盐水输注期间，无论使用何种葡萄糖示踪剂，葡萄糖周转率的估计值均相似。放射性葡萄糖示踪剂和血浆的高效液相色谱显示存在氚化非葡萄糖污染物。虽然污染物仅占[6- 3 H]葡萄糖输注液中放射性的1.5%，但其清除率比[6- 3 H]葡萄糖低10倍（P <0.001）。这导致在血浆中蓄积，在胰岛素或盐水输注期间，污染物分别占通常假定的血浆葡萄糖放射性的16.6 ± 2.09和10.8 ± 0.9%（P <0.01）。当校正污染物的存在时，在胰岛素输注期间用[6- 3 H]葡萄糖测定的葡萄糖周转率（9.5 ± 0.6 mg · kg−1 · min−1）与葡萄糖输注速率或用[6- 14 C]葡萄糖测定的葡萄糖周转率不再不同。因此，用传统方法分析血浆放射性和市售示踪剂时观察到的胰岛素输注期间葡萄糖周转率低估和葡萄糖生成率负值是人为增加[6- 3 H]葡萄糖比活度的结果。用[6，6 - 2 H2]葡萄糖低估葡萄糖周转的病因仍有待确定。
Recent studies indicate that hydrogen-labeled glucose tracers underestimate glucose turnover in humans under conditions of high flux. The cause of this underestimation is unknown. To determine whether the error is time-, pool-, model-, or insulin-dependent, glucose turnover was measured simultaneously with [6-3H]-, [6,6-2H2]-, and [6-14C]glucose during a 7-h infusion of either insulin (1 mU · kg−1 · min−1) or saline. During the insulin infusion, steady-state glucose turnover measured with both [6-3H]glucose (8.0 ± 0.5 mg · kg−1 · min−1) and [6,6-2H2]glucose (7.6 ± 0.5 mg kg−1 min−1) was lower (P < .01) than either the glucose infusion rate required to maintain euglycemia (9.8 ± 0.6 mg · kg−1 · min−1) or glucose turnover determined with [6-14 C]glucose and corrected for Cori cycle activity (9.8 ± 0.7 mg · kg−1 · min1). Consequently “negative” glucose production rates (P <.01) were obtained with either [6-3 H]- or [6,6-2 H2]-but not [6-14 C]glucose. The difference between turnover estimated with [6-3 H]glucose and actual glucose disposal (or 14C glucose flux) did not decrease with time and was not dependent on duration of isotope infusion. During saline infusion, estimates of glucose turnover were similar regardless of the glucose tracer used. High-performance liquid chromatography of the radioactive glucose tracer and plasma revealed the presence of a tritiated nonglucose contaminant. Although the contaminant represented only 1.5% of the radioactivity in the [6-3H]glucose infusate, its clearance was 10-fold less (P <.001) than that of [6-3H]glucose. This resulted in accumulation in plasma, with the contaminant accounting for 16.6 ± 2.09 and 10.8 ± 0.9% of what customarily is assumed to be plasma glucose radioactivity during the insulin or saline infusion, respectively (P < .01). When corrected for the presence of the contaminant, glucose turnover determined with [6-3H]glucose during insulin infusion (9.5 ± 0.6 mg · kg−1 · min−1) no longer differed from either the glucose infusion rate or that determined with [6-14C]glucose. Therefore, the underestimation of glucose turnover during insulin infusion and negative glucose production rates observed with traditional methods to analyze plasma radioactivity and commercially available tracers is the result of an artifactual increase in [6-3H]glucose specific activity. The etiology of the underestimation of glucose turnover with [6,6-2H2]glucose remains to be determined.
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