Landau B R, Chandramouli V, Schumann W C, Ekberg K, Kumaran K, Kalhan S C, Wahren J
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4951, USA.
Diabetologia. 1995 Jul;38(7):831-8. doi: 10.1007/s001250050360.
Normal subjects, fasted 60 h, and patients with insulin-dependent diabetes mellitus (IDDM), withdrawn from insulin and fasted overnight, were given phenylacetate orally and intravenously infused with [3-14C]lactate and 13C-bicarbonate. Rates of hepatic gluconeogenesis relative to Krebs cycle rates were estimated from the 14C distribution in glutamate from urinary phenylacetylglutamine. Assuming the 13C enrichment of breath CO2 was that of the CO2 fixed by pyruvate, the enrichment to be expected in blood glucose, if all hepatic glucose production had been by gluconeogenesis, was then estimated. That estimate was compared with the actual enrichment in blood glucose, yielding the fraction of glucose production due to gluconeogenesis. Relative rates were similar in the 60-h fasted healthy subjects and the diabetic patients. Conversion of oxaloacetate to phosphoenolpyruvate was two to eight times Krebs cycle flux and decarboxylation of pyruvate to acetyl-CoA, oxidized in the cycle, was less than one-30th the fixation by pyruvate of CO2. Thus, in estimating the contribution of a gluconeogenic substrate to glucose production by measuring the incorporation of label from the labelled substrate into glucose, dilution of label at the level of oxaloacetate is relatively small. Pyruvate cycling was as much as one-half the rate of conversion of pyruvate to oxaloacetate. Glucose and glutamate carbons were derived from oxaloacetate formed by similar pathways if not from a common pool. In the 60-h fasted subjects, over 80% of glucose production was via gluconeogenesis. In the diabetic subjects the percentages averaged about 45%.
对禁食60小时的正常受试者以及停用胰岛素并禁食过夜的胰岛素依赖型糖尿病（IDDM）患者口服苯乙酸，并静脉输注[3-¹⁴C]乳酸和¹³C-碳酸氢盐。根据尿苯乙酰谷氨酰胺中谷氨酸的¹⁴C分布估算肝糖异生相对于三羧酸循环速率的比率。假设呼出二氧化碳的¹³C富集度就是丙酮酸固定的二氧化碳的富集度，那么如果所有肝葡萄糖生成均通过糖异生，就可以估算出血糖中预期的富集度。将该估算值与血糖中的实际富集度进行比较，得出糖异生所致葡萄糖生成的比例。60小时禁食的健康受试者和糖尿病患者的相对速率相似。草酰乙酸向磷酸烯醇式丙酮酸的转化是三羧酸循环通量的2至8倍，丙酮酸向乙酰辅酶A的脱羧反应（在循环中被氧化）不到丙酮酸固定二氧化碳的1/30。因此，在通过测量标记底物中标记物掺入葡萄糖来估算糖异生底物对葡萄糖生成的贡献时，草酰乙酸水平的标记物稀释相对较小。丙酮酸循环速率高达丙酮酸向草酰乙酸转化速率的一半。如果不是来自共同池，葡萄糖和谷氨酸的碳源自通过相似途径形成的草酰乙酸。在禁食60小时的受试者中，超过80%的葡萄糖生成是通过糖异生。在糖尿病受试者中，该百分比平均约为45%。
