Role of glutamine as a glucose precursor in fasting humans
Role of glutamine as a glucose precursor in fasting humans
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DOI：
10.2337/diabetes.46.10.1535
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发表时间：
1997-10-01
期刊：
影响因子：
7.7
通讯作者：
Darmaun, D
中科院分区：
文献类型：
--
作者：
Hankard, RG;Haymond, MW;Darmaun, D
最近，在吸收后的人体输注C-14标记的谷氨酰胺的过程中，有证据表明标记碳显著地结合到血糖中。血糖的这种标记可以通过两个不同的过程发生：1)通过谷氨酰胺将谷氨酰胺碳结合到葡萄糖中，通过谷氨酰胺进入α-酮戊二酸的Krebs循环；或者2)通过简单地固定标记的CO2，通过标记的谷氨酰胺的氧化而产生。因此，这些研究旨在确定：1)谷氨酰胺是否有助于糖异生，而不是仅仅通过固定二氧化碳；如果是，2)碳从谷氨酰胺转移到葡萄糖的表观转移是否随着禁食而增加。研究人员连续两天对健康成年人进行研究：一次是在禁食一夜(18小时)之后，另一次是在禁食第二天(42小时禁食)。在每个研究日，受试者同时接受D-[6，6-H-2(2)]葡萄糖、L-[3，4-C-13(2)]谷氨酰胺和L-[1-C-14]亮氨酸的5h输注。通过C-13在血糖中的出现来估计葡萄糖中谷氨酰胺碳的表观掺入速率；从血浆[H-2(2)]葡萄糖和[C-13(2)]谷氨酰胺的富集物中分别测定葡萄糖和谷氨酰胺产生率(出现率[R-a])。C-14在血糖中的出现被用来修正由于CO2固定而测得的谷氨酰胺向葡萄糖的碳转移速率。我们观察到，在标记的谷氨酰胺对糖异生的明显贡献中，只有4%是标记的二氧化碳固定的结果，而96%似乎是通过其他途径发生的。我们还观察到在禁食18-42h期间，1)蛋白质分解对谷氨酰胺生产的相对贡献增加，而从头合成的相对贡献减少；2)谷氨酰胺对葡萄糖生产的表观贡献从占总葡萄糖R-a的8+/-1上升到16+/-3%；以及3)谷氨酰胺对糖异生的相对贡献保持不变。从目前的数据中，还不能确定从谷氨酰胺到葡萄糖的表观碳转移在多大程度上代表了谷氨酰胺对葡萄糖异生作用的真正贡献，或者仅仅是三氯乙酸循环和葡萄糖异生途径之间的碳交换。然而，这些发现与谷氨酰胺在禁食人类中作为葡萄糖重要前体的作用是一致的。
Recently, significant incorporation of labeled carbon into plasma glucose was documented during infusion of C-14-labeled glutamine in postabsorptive humans. Such labeling of plasma glucose can occur as a result of two different processes: either 1) through incorporation of glutamine carbon into glucose via glutamine entering Krebs cycle at alpha-ketoglutarate or 2) through simple fixation of labeled CO2 resulting from oxidation of labeled glutamine. Therefore, these studies were designed to determine 1) whether glutamine contributes carbon to gluconeogenesis other than through mere CO2 fixation, and, if so, 2) whether the apparent transfer of carbon from glutamine to glucose increases with fasting. Fight healthy adults were studied on two consecutive days: once after an overnight (18-h) fast and again on the second day of fasting (42-h fast). On each study day, subjects received a simultaneous 5-h infusion of D-[6,6-H-2(2)]glucose, L-[3,4-C-13(2)]glutamine, and L-[1-C-14]leucine. Apparent rates of incorporation of glutamine carbon into glucose were estimated from the appearance of C-13 into plasma glucose; glucose and glutamine production rates (appearance rate [R-a]) were determined from plasma [H-2(2)]glucose and [C-13(2)]glutamine enrichments, respectively. The appearance of C-14 into plasma glucose was used to correct the measured rates of carbon transfer from glutamine to glucose as a result of CO2 fixation. We observed that of the apparent contribution of labeled glutamine to gluconeogenesis, only 4% occurred as a result of fixation of labeled CO2, while 96% seemed to occur through other routes. We also observed that between 18 and 42 h of fasting, 1) the relative contribution of protein breakdown to glutamine production was enhanced, while that of de novo synthesis declined; 2) the apparent contribution of glutamine to glucose production rose from 8 +/- 1 to 16 +/- 3% of overall glucose R-a; and 3) the relative apparent contribution of glutamine to gluconeogenesis remained constant. From the current data, it cannot be ascertained to what extent the apparent carbon transfer from glutamine to glucose represents a true contribution of glutamine to gluconeogenesis or mere carbon exchange between the trichloroacetic acid cycle and the gluconeogenic pathway. These findings are nevertheless compatible with a role of glutamine as a significant precursor of glucose in fasting humans.