Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test

Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test
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DOI:
10.1016/s0003-2697(02)00709-1
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发表时间:
2003-04-15
影响因子:
2.9
通讯作者:
Kurland, IJ
Kurland, IJ
中科院分区:
生物学4区
文献类型:
--
作者:
Xu, J;Lee, WNP;Kurland, IJ

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葡萄糖和 6-磷酸葡萄糖之间的葡萄糖循环增加是 11 型糖尿病中胰岛素抵抗和高血糖的特征。传统上,葡萄糖循环是通过分别输注[2-H-3]葡萄糖和[6-H-3]葡萄糖所测量的肝葡萄糖输出之间的差异来确定的。我们展示了一种通过腹膜内葡萄糖耐量试验(IPGTT)确定肝脏葡萄糖回收的新方法。以1mg/g体重向4个月大的C57BL/6小鼠施用单一示踪剂[1, 2-C-13(2)]葡萄糖(M2葡萄糖同位素异构体)。通过血浆M I 葡萄糖同位素异构体的出现来监测肝葡萄糖再循环,该葡萄糖同位素异构体是由戊糖循环对肝脏中M2葡萄糖同位素异构体的作用产生的。 M2 初始富集率为 56%,3 h 后降至 13%,M1 富集在 2 h 时达到峰值。血浆M1/M2葡萄糖的比率随时间线性增加至大约25%,并且M1/M2比率对时间的回归给出斜率,称为体内葡萄糖依赖性无用再循环率常数k(HR)。 k(HR) 估计葡萄糖/6-磷酸葡萄糖的无效循环,以及通过戊糖循环的葡萄糖再循环。这些观察结果表明,使用单一稳定同位素示踪剂的 IPGTT 期间存在复杂的底物循环。 (C) 2003 年爱思唯尔科学(美国)。版权所有。
Increased glucose cycling between glucose and glucose-6-phosphate is characteristic of insulin resistance and hyperglycemia seen with Type 11 diabetes. Traditionally, glucose cycling is determined by the difference between hepatic glucose output measured with separate [2-H-3]glucose and [6-H-3]glucose infusions. We demonstrate a novel method for determining hepatic glucose recycling from an intraperitoneal glucose tolerance test (IPGTT). A single tracer, [1, 2-C-13(2)]glucose (a M2 glucose isotopomer), was administered at I mg/g body weight to 4-month-old C57BL/6 mice. Hepatic glucose recycling was monitored by the appearance of a plasma M I isotopomer of glucose, which is produced by the action of the pentose cycle on the M2 glucose isotopomer in the liver. The initial M2 enrichment was 56% and decreased to 13% at the end of 3 h, and the M1 enrichment peaked at 2 h. The ratio of plasma M1/M2 glucose increased linearly with time to similar to25%, and the regression of the M1/M2 ratio against time gives a slope, termed the in vivo glucose-dependent futile recycling rate constant k(HR). k(HR) estimates glucose/glucose-6-phosphate futile cycling, along with glucose recycling through the pentose cycle. These observations demonstrate complex substrate cycling during an IPGTT using a single stable isotope tracer. (C) 2003 Elsevier Science (USA). All rights reserved.