Institute of Biomedical Engineering, National Research Council, Padua, Italy.
Metabolism. 2011 Nov;60(11):1627-33. doi: 10.1016/j.metabol.2011.03.017. Epub 2011 May 31.
Although the use of radioisotopes in the investigation of glucose metabolism dates back more than 50 years, several relevant quantitative aspects have not been definitively determined. These include the volume of distribution (V(d)) of glucose and recycling of glucose radioisotopes from liver glycogen. These problems are further complicated by methodological issues such as the following: (1) glucose tracers have different metabolic fates that may influence volume estimates, and (2) the calculation method needs to be based on physical principles to avoid some limitations of compartmental models. To address these issues, we administered boluses of an extracellular marker ([1-(14)C]-l-glucose, 30 μCi) and 2 glucose tracers ([2-(3)H]-d-glucose and [3-(3)H]-d-glucose, 120 μCi of each), followed by a 1-mg glucagon bolus (in the presence of somatostatin) 245 minutes later, in conscious beagles to account for potential problems in recycling of the label through glycogen. We used modeling methods based on physical principles (circulatory model), which yield volume estimates with a clear physiological interpretation. Glucose V(d) (mL/kg) were 204 ([1-(14)C]-l-glucose), 191 ([2-(3)H]-d-glucose), and 206 ([3-(3)H]-d-glucose). These values were not different and correlated. The amount of recycled [3-(3)H]-d-glucose in response to glucagon was small (∼1.7% of the injected tracer dose). An additional result of this analysis is the determination of the parameters of the circulatory model in beagles for the standard [3-(3)H]-d-glucose tracer. Using multiple tracers in beagles and calculation methods based on physical principles, we have provided direct proof that the glucose V(d) equals the extracellular space in beagles under basal conditions.
尽管放射性同位素在葡萄糖代谢研究中的应用可以追溯到 50 多年前，但仍有几个相关的定量问题尚未得到明确确定。这些问题包括葡萄糖的分布容积（V(d)）和肝糖原中葡萄糖放射性同位素的再循环。这些问题进一步复杂化，还涉及到以下方法学问题：（1）葡萄糖示踪剂具有不同的代谢命运，这可能会影响体积估计；（2）计算方法需要基于物理原理，以避免房室模型的一些限制。为了解决这些问题，我们在清醒的比格犬中给予细胞外示踪剂（[1-(14)C]-l-葡萄糖，30 μCi）和 2 种葡萄糖示踪剂（[2-(3)H]-d-葡萄糖和[3-(3)H]-d-葡萄糖，各 120 μCi）的推注，然后在 245 分钟后给予 1 毫克胰高血糖素推注（在生长抑素存在的情况下），以说明通过糖原再循环标签的潜在问题。我们使用基于物理原理的建模方法（循环模型），该方法可提供具有明确生理解释的容积估计值。葡萄糖 V(d)（mL/kg）分别为 204（[1-(14)C]-l-葡萄糖）、191（[2-(3)H]-d-葡萄糖）和 206（[3-(3)H]-d-葡萄糖）。这些值没有差异且相关。胰高血糖素引起的[3-(3)H]-d-葡萄糖再循环量很小（约为注射示踪剂剂量的 1.7%）。该分析的另一个结果是确定了比格犬中标准[3-(3)H]-d-葡萄糖示踪剂循环模型的参数。在比格犬中使用多种示踪剂和基于物理原理的计算方法，我们提供了直接证据，证明在基础条件下，比格犬的葡萄糖 V(d)等于细胞外空间。
