USE OF (H2O)-H-2 FOR ESTIMATING RATES OF GLUCONEOGENESIS - APPLICATION TO THE FASTED STATE

USE OF (H2O)-H-2 FOR ESTIMATING RATES OF GLUCONEOGENESIS - APPLICATION TO THE FASTED STATE
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DOI:
10.1172/jci117635
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发表时间:
1995-01-01
影响因子:
15.9
通讯作者:
KALHAN, SC
KALHAN, SC
中科院分区:
医学1区
文献类型:
--
作者:
LANDAU, BR;WAHREN, J;KALHAN, SC

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介绍了一种估计糖异生对葡萄糖生产的贡献的方法。 (H2O)-H-2 口服给药,以实现体内水中 0.5% 的氘富集。在与血糖和尿水中的碳 2 和碳 6 结合的氢中测定富集度,在六亚甲基四胺中测定葡萄糖碳 6 的富集度,六亚甲基四胺是由葡萄糖的高碘酸盐氧化产生的甲醛形成的。在通过将氢从葡萄糖经山梨糖醇酶促转移至丙酮酸而形成的乳酸盐中测定碳2处的富集。糖异生对葡萄糖产生的贡献分数等于碳6处的富集与碳2处或尿水中的富集的比率。应用该方法,健康受试者禁食14小时后糖异生的贡献为23-42%,禁食42小时后增加至59-84%。碳2的富集度与尿水中的碳2的富集度为1.12+/-0.13。因此,满足了6-P己糖异构化过程中氢达到平衡的假设。给予健康受试者的由[3-H-3,3-C-14]乳酸盐形成的葡萄糖中的H-3/C-14比率是乳酸盐中的0.1至0.2。因此,在糖异生过程中,与碳 6 结合的氢与体内水分的平衡已完成 80-90%,因此糖异生作用被低估了 10-20%。这些估计中不包括甘油对糖异生的贡献。该方法适用于人类在安全剂量 (H2O)-H-2 下的糖异生研究。
A method is introduced for estimating the contribution of gluconeogenesis to glucose production. (H2O)-H-2 is administered orally to achieve 0.5% deuterium enrichment in body water, Enrichments are determined in the hydrogens bound to carbons 2 and 6 of blood glucose and in urinary water, Enrichment at carbon 6 of glucose is assayed in hexamethylenetetramine, formed from formaldehyde produced by periodate oxidation of the glucose. Enrichment at carbon 2 is assayed in lactate formed by enzymatic transfer of the hydrogen from glucose via sorbitol to pyruvate, The fraction gluconeogenesis contributes to glucose production equals the ratio of the enrichment at carbon 6 to that at carbon 2 or in urinary water. Applying the method, the contribution of gluconeogenesis in healthy subjects was 23-42% after fasting 14 h, increasing to 59-84% after fasting 42 h. Enrichment at carbon 2 to that in urinary water was 1.12+/-0.13. Therefore, the assumption that hydrogen equilibrated during hexose-6-P isomerization was fulfilled. The H-3/C-14 ratio in glucose formed from [3-H-3,3-C-14]lactate given to healthy subjects was 0.1 to 0.2 of that in the lactate. Therefore equilibration during gluconeogenesis of the hydrogen bound to carbon 6 with that in body water was 80-90% complete, so that gluconeogenesis is underestimated by 10-20%. Glycerol's contribution to gluconeogenesis is not included in these estimates. The method is applicable to studies in humans of gluconeogenesis at safe doses of (H2O)-H-2.