MATHEMATICAL-MODELS OF INSULIN-SECRETION IN PHYSIOLOGICAL AND CLINICAL INVESTIGATIONS
MATHEMATICAL-MODELS OF INSULIN-SECRETION IN PHYSIOLOGICAL AND CLINICAL INVESTIGATIONS
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DOI：
10.1016/0169-2607(94)90059-0
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发表时间：
1994-01-01
影响因子：
6.1
通讯作者：
PACINI, G
中科院分区：
文献类型：
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作者：
PACINI, G
用于测量胰岛素浓度的放射免疫测定法的发现刺激了几项聪明的研究，这些研究在体外和体内都显示了β细胞对葡萄糖刺激的特殊双相反应模式。生理学家接受了用数学模型描述这些数据的挑战，引入了一些工具，为医学和生物学研究科学家提供了有关胰岛素分泌复杂过程本质的进一步知识。因此，开发了模拟模型来解释系统行为的不同特征之间的相互依赖性，以便更好地理解它们并为进一步的研究制定假设。这些模型的缺点（相当复杂的数学结构，不可识别性等）限制了它们的使用，主要是作为教学工具。在临床环境中使用模型需要从实验测试中尽可能简单地个性化单个受试者的参数集。这导致了胰岛素外观和动力学的最小模型的发展。该模型是完全可识别的，因此能够提供胰岛素行为的个性化图像，在（经常取样的）静脉葡萄糖耐量试验期间提供激素分泌的见解。然而，该模型分析了全身胰岛素浓度数据，仅提供了肝后胰岛素输送的信息。由于肝脏吸收了释放的激素的50%以上，因此有必要进一步评估胰岛素的分泌，即分析c肽的行为，c肽与胰岛素同时释放，但不被肝脏提取。最后一代模型实际上是系统c肽动力学的描述符，并用于重建其分泌，假设其摩尔等于胰岛素的分泌。基于这一原理，主要有三种肝前胰岛素出现模型被开发并用于临床研究。
The discovery of the radioimmunoassay for the measurement of insulin concentration stimulated several clever studies which showed, both in vitro and in vivo, the peculiar biphasic pattern of the beta-cell response to glucose stimulation. Physiologists took the challenge to describe with mathematical models those data, introducing tools that provided medical and biological research scientists with further knowledge of the nature of the complex processes involved in insulin secretion. Simulation models were therefore developed to account for the dependence on each other of the different features of the system behaviour to better understand them and to formulate hypotheses for further investigations. The disadvantages of these models (rather complex mathematical structure, unidentifiability, etc.) limited their use to a few applications, mostly as teaching tools. The use of models in the clinical setting required the individualization of the parameter set for a single subject from an experimental test as simple as possible. This led to the development of the minimal model of insulin appearance and kinetics. This model, fully identifiable, thus enables the furnishing of a personalized picture of insulin behaviour, providing insights on hormone secretion during a (frequently sampled) intravenous glucose tolerance test. However, this model analyzed systemic insulin concentration data and gave information only on post-hepatic insulin delivery. Since the liver takes up more than 50% of the released hormone, a further step was necessary to evaluate insulin secretion, i.e. the analysis of the behaviour of C-peptide, which is released equimolarly with insulin, but is not extracted by the liver. The last generation models are in fact descriptors of the systemic C-peptide dynamics, and are used to reconstruct its secretion which is assumed to be molarly equal to that of insulin. Mainly three models of pre-hepatic insulin appearance, based on this principle, have been developed and used in clinical studies.