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输注持续时间和同位素标记选择对葡萄糖稳态中同位素再循环的影响。

Impact of duration of infusion and choice of isotope label on isotope recycling in glucose homeostasis.

作者信息

Tigas Stelios K, Sunehag Agneta L, Haymond Morey W

机构信息

Baylor College of Medicine, Children's Nutrition Research Center, USDA/ARS, Department of Pediatrics-Nutrition, Houston, Texas 77030, USA.

出版信息

Diabetes. 2002 Nov;51(11):3170-5. doi: 10.2337/diabetes.51.11.3170.

DOI:10.2337/diabetes.51.11.3170
PMID:12401707
Abstract

The purposes of this study were to quantify the impact of the duration of infusion and choice of stable isotope of glucose on measures of glucose rate of appearance (glucose R(a)) and to determine whether the differences observed were due to tracer recycling via the glycogen pool (direct pathway) or gluconeogenesis (indirect pathway). Six healthy adult volunteers were studied on four occasions in the postabsorptive state during infusions of [1-(13)C]glucose and [6,6-(2)H(2)]glucose: 2.5-h infusion of both (A), and 2.5-h infusion of one (B) and 14.5-h infusion of the other isotope (C), and 5-h infusion of [6,6-(2)H(2)]glucose and 2.5-h infusion of [1-(13)C]glucose (D). Infusion of both isotopes for 2.5 h resulted in similar glucose R(a) values. When compared with a 14.5-h infusion, the 2.5-h glucose tracer infusion overestimated glucose R(a) by 26-35%. Glucose (13)C recycled via the Cori cycle, resulting in slower decay from the plasma pool and longer half-life of [1-(13)C]glucose compared with [6,6-(2)H(2)]glucose. There was no detectable release of [(13)C]glucose or [(2)H(2)]glucose tracer into the plasma pool after administration of glucagon. These data demonstrate that glucose R(a) varies not as a result of isotope cycling but as a result of differences in duration of isotope infusion regardless of the isotope used. This is most likely due to incomplete isotope and substrate equilibration with the 2.5-h infusion. The potential error was reduced by nearly 80% using a 5-h infusion of [6,6-(2)H(2)]glucose. These studies demonstrate that the duration of isotope infusion has significantly greater impact on quantitation of glucose R(a) than does the selection of isotope.

摘要

本研究的目的是量化输注持续时间和葡萄糖稳定同位素的选择对葡萄糖出现率(葡萄糖R(a))测量值的影响,并确定观察到的差异是由于示踪剂通过糖原池的再循环(直接途径)还是糖异生(间接途径)所致。在六名健康成年志愿者处于吸收后状态时,对其进行了四次研究,期间分别输注[1-(13)C]葡萄糖和[6,6-(2)H(2)]葡萄糖:两种同位素均输注2.5小时(A),一种同位素输注2.5小时而另一种输注14.5小时(B),以及[6,6-(2)H(2)]葡萄糖输注5小时和[1-(13)C]葡萄糖输注2.5小时(D)。两种同位素均输注2.5小时导致相似的葡萄糖R(a)值。与14.5小时输注相比,2.5小时的葡萄糖示踪剂输注使葡萄糖R(a)高估了26%至35%。葡萄糖通过科里循环进行(13)C再循环,导致与[6,6-(2)H(2)]葡萄糖相比,其从血浆池中衰减更慢,[1-(13)C]葡萄糖的半衰期更长。给予胰高血糖素后,没有检测到[(13)C]葡萄糖或[(2)H(2)]葡萄糖示踪剂释放到血浆池中。这些数据表明,葡萄糖R(a)的变化不是由于同位素循环,而是由于同位素输注持续时间的差异,无论使用何种同位素。这很可能是由于2.5小时输注时同位素和底物未完全平衡所致。使用[6,6-(2)H(2)]葡萄糖输注5小时可使潜在误差降低近80%。这些研究表明,同位素输注持续时间对葡萄糖R(a)定量的影响远大于同位素的选择。

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