ESTIMATION OF ENDOGENOUS GLUCOSE-PRODUCTION DURING HYPERINSULINEMIC-EUGLYCEMIC GLUCOSE CLAMPS - COMPARISON OF UNLABELED AND LABELED EXOGENOUS GLUCOSE INFUSATES
ESTIMATION OF ENDOGENOUS GLUCOSE-PRODUCTION DURING HYPERINSULINEMIC-EUGLYCEMIC GLUCOSE CLAMPS - COMPARISON OF UNLABELED AND LABELED EXOGENOUS GLUCOSE INFUSATES
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DOI：
10.2337/diabetes.36.8.914
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发表时间：
1987-08-01
期刊：
影响因子：
7.7
通讯作者：
VRANIC, M
中科院分区：
文献类型：
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作者：
FINEGOOD, DT;BERGMAN, RN;VRANIC, M
示踪方法已广泛应用于估计内源性葡萄糖生产（Ra）在正常血糖葡萄糖钳。这种方法的准确性受到质疑，因为观察到胰岛素水平高时Ra的显着负估计。我们进行了高胰岛素治疗（300 .mu）。U/ml)-正常犬正常血糖夹夹180分钟，并比较标准方法，未标记的外源性葡萄糖输注（冷GINF方案，n = 12）和新方法，在外源性葡萄糖中加入示踪剂（D-[3-3H]葡萄糖）用于夹夹（热GINF方案，n = 10）。两种方案的血浆葡萄糖、胰岛素和胰高血糖素浓度以及葡萄糖输注速率相似。血浆葡萄糖比活性为20。在冷GINF研究中，1%的基础（在120-180分钟），44.1% +-。3到187 .+-。在热GINF研究中5%的基础。采用斯蒂尔的单室固定池体积模型，冷GINF研究的Ra为-2.4 .+-。0.7 mg.cntdot。min - 1. cntdot。kg-1在25 min时呈显著阴性，直至110 min （P < 0.05）。在热GINF研究中，Ra从未显著小于零（P < 0.05），并且在20-90 min时大于冷GINF研究（P < 0.05）。与冷GINF研究相比，热GINF研究的-间（78%）和-内（40%）实验差异明显较小。采用一室模型的另一种方法（回归方法）允许可变和可估计的有效分布体积，产生的Ra估计值从基础上抑制了60-100%。综上所述，葡萄糖动力学的单室固定池体积模型不适用于正糖葡萄糖钳夹期间Ra的估计。从单室模型估计Ra的两种新策略，热GINF协议和回归方法计算，比目前使用的方法产生更准确和生理上合理的Ra估计。
Tracer methodology has been applied extensively to the estimation of endogenous glucose production (Ra) during euglycemic glucose clamps. The accuracy of this approach has been questioned due to the observation of significantly negative estimates for Ra when insulin levels are high. We performed hyperinsulinemic (300 .mu.U/ml)-euglycemic glucose clamps for 180 min in normal dogs and compared the standard approach, an unlabeled exogenous glucose infusate (cold GINF protocol, n = 12), to a new approach in which a tracer (D-[3-3H]glucose) was added to the exogenous glucose used for clamping (hot GINF protocol, n = 10). Plasma glucose, insulin and glucagon concentrations, and glucose infusion rates were similar for the two protocols. Plasma glucose specific activity was 20 .+-. 1% of basal (at 120-180 min) in the cold GINF studies, and 44 .+-. 3 to 187 .+-. 5% of basal in the hot GINF studies. With the one-compartment, fixed pool volume model of Steele, Ra for the cold GINF studies was -2.4 .+-. 0.7 mg.cntdot. min-1.cntdot. kg-1 at 25 min and remained significantly negative until 110 min (P < .05). For the hot GINF studies, Ra was never significantly less than zero (P < .05) and was greater than in the cold GINF studies at 20-90 min (P < .05). There was substantially less between-(78%) and within- (40%) experiment variation for the hot GINF studies compared with the cold GINF studies. An alternate approach (regression method) to the application of the one-compartment model, which allows for a variable and estimable effective distribution volume, yielded Ra estimates that were suppressed 60-100% from basal. In conclusion, the one-compartment, fixed pool volume model of glucose kinetics is inadequate for the estimation of Ra during euglycemic glucose clamps. Two new strategies for estimating Ra from the one-compartment model, the hot GINF protocol and the regression method calculation, yielded more accurate and physiologically plausible estimates of Ra than currently used methodolgy.