Glucose turnover in chronic uremia: increased recycling with diminished oxidation of glucose.
Glucose turnover in chronic uremia: increased recycling with diminished oxidation of glucose.
复制标题
慢性尿毒症中的葡萄糖周转：随着葡萄糖氧化的减少而增加循环。
DOI：
10.1016/0026-0495(83)90064-1
复制
发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Savin,SM
中科院分区：
文献类型：
--
作者：
Kalhan,SC;Ricanati,ES;Tserng,KY;Savin,SM
在8例慢性尿毒症患者中评价了慢性肾功能衰竭和血液透析对葡萄糖周转率、葡萄糖碳循环和葡萄糖氧化的影响。6例正常人作为对照组。在7名尿毒症受试者接受血液透析3至18个月后，重复了这些研究。通过预充恒速输注给予葡萄糖13 C（μ l），并通过质谱法测量整个葡萄糖分子（m + 6）的同位素富集，即用13 C标记的葡萄糖的所有6个碳原子和葡萄糖的C1原子在血浆中的同位素富集。据推测，葡萄糖分子的C1原子代表了单个葡萄糖碳的13 C富集。从血浆中葡萄糖13 C（μ l）质量（m + 6）的稀释度估计葡萄糖产生的“真实”速率。与整个葡萄糖分子（m + 6）相比，示踪碳的再循环导致葡萄糖分子的C1原子的13 C富集增加和葡萄糖周转率的低估（“表观”）。葡萄糖碳循环是从葡萄糖周转的“真实”和“表观”速率之间的差异来估计的。通过比较呼出CO2中13 C的富集与血浆葡萄糖碳的富集来定量葡萄糖对呼吸CO2的贡献。尿毒症受试者和对照受试者空腹过夜后的血糖浓度相似（分别为72.3 ± 9.5和79.0 ± 9.5 mg/dL;平均值± SD）。通过血浆葡萄糖分子C1原子的可逆示踪剂13 C富集测量的“表观”葡萄糖产生速率在尿毒症受试者中降低，而“真实”葡萄糖产生速率在两组中相似（正常：2.02 ± 0.19 mg/kg · min;尿毒症：2.19 ± 0.53 mg/kg · min）。葡萄糖碳循环占对照组总葡萄糖产量的3.3%至26.2%。在8名尿毒症受试者中，有7名受试者的葡萄糖碳循环占葡萄糖周转率的28.6%至41.7%。在第8例尿毒症患者中，葡萄糖碳循环占葡萄糖周转的4.7%。慢性尿毒症患者葡萄糖对呼吸CO2的贡献显著降低（P< 0.02），并与葡萄糖转换率相关（r= 0.51，P = 0.05）。慢性血液透析对尿毒症患者的葡萄糖动力学没有影响。它导致葡萄糖分布容积减少（无统计学显著性）和葡萄糖浓度相应增加，因此尿毒症受试者的葡萄糖池大小保持不变。在另外三名受试者中，通过测量血液透析后24和48小时的葡萄糖动力学来检查血液透析的急性效应。未观察到血液透析对葡萄糖产生和利用的显著影响。尿毒症患者血浆胰岛素浓度均显著高于正常人。我们的结论是，在人类慢性尿毒症中，过夜禁食后（1）葡萄糖产生速率不变;（2）葡萄糖碳循环增加，而葡萄糖氧化减少;（3）血液透析对这些变量没有影响。由于所有尿毒症受试者的胰岛素浓度增加，这些数据进一步反映了胰岛素作用的降低，可能是在丙酮酸脱氢酶水平上。
The effects of chronic renal failure and hemodialysis on the glucose turnover rate, glucose carbon recycling, and glucose oxidation were evaluated in eight chronically uremic subjects. Six normal subjects served as controls. The studies were repeated in seven uremic subjects after they had been established on hemodialysis for 3 to 18 months. Glucose13C (ul) was administered by a prime-constant-rate infusion, and the isotopic enrichment of the whole glucose molecule (m + 6), ie, all six carbon atoms of glucose labeled with13C and that of the C1 atom of glucose in the plasma were measured by mass spectrometry. It was assumed that the C1 atom of the glucose molecule represented the13C enrichment of the individual glucose carbons. The “true” rate of glucose production was estimated from the dilution of the glucose13C (ul) mass (m + 6) in the plasma. In contrast to the whole glucose molecule (m + 6), recycling of tracer carbon resulted in an increased13C enrichment of the C1 atom of the glucose molecule and an underestimation of glucose turnover (“apparent”). Glucose carbon recycling was estimated from the difference between the “true” and “apparent” rates of glucose turnover. The contribution of glucose to respiratory CO2was quantified by comparing the13C enrichment of expired CO2with that of the plasma glucose carbon. The plasma glucose concentration after an overnight fast was similar in the uremic and control subjects (72.3 ± 9.5 and 79.0 ± 9.5 mg/dL, respectively; mean ± SD). The “apparent” rate of glucose production, as measured by the reversible tracer13C enrichment of the C1 atom of the plasma glucose molecule, was decreased in the uremic subjects, while the “true” rates of glucose production were similar in both groups (normal: 2.02 ± 0.19 mg/kg · min; uremic: 2.19 ± 0.53 mg/kg · min). Glucose carbon recycling contributed between 3.3% and 26.2% to the total glucose production in the controls. In seven out of eight uremic subjects, glucose carbon recycling ranged between 28.6% and 41.7% of glucose turnover. Glucose carbon recycling was 4.7% of glucose turnover in the eighth uremic subject. The contribution of glucose to respiratory CO2was significantly reduced in the chronically uremic subjects (P< 0.02) and correlated with the rate of glucose turnover (r= 0.51,P= 0.05). Chronic hemodialysis had no effect on glucose kinetics in the uremic subjects. It caused a decrease (not statistically significant) in the volume of distribution of glucose and a corresponding increase in the glucose concentration, so that the glucose pool size remained unchanged in the uremic subjects. In three additional subjects, the acute effects of hemodialysis were examined by measuring glucose kinetics at 24 and 48 hours after hemodialysis. No significant effect of hemodialysis on glucose production and utilization was observed. The plasma insulin concentration was significantly increased in all uremic subjects compared with the normal subjects. We conclude that in chronic uremia in humans, after an overnight fast (1) the glucose production rate is unchanged; (2) glucose carbon recycling is increased, while glucose oxidation is decreased; and (3) hemodialysis has no effect on these variables. As the insulin concentration was increased in all uremic subjects, these data further reflect decreased insulin action, possibly at the level of pyruvate dehydrogenase.