Rudenski A S, Matthews D R, Levy J C, Turner R C
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
Metabolism. 1991 Sep;40(9):908-17. doi: 10.1016/0026-0495(91)90065-5.
A mathematical model of normal glucose/insulin homoeostasis has been based on the known, experimentally determined responses of the liver and periphery to different glucose/insulin concentrations. Different defects of glucose resistance and insulin resistance have been applied to the model to investigate the degree to which these abnormalities could successfully predict the range of fasting glucose and insulin values found in normal, obese, and diabetic subjects. Modeling glucose resistance or insulin resistance at the liver or the periphery alone did not increase the plasma glucose to levels observed in diabetes, even when associated with marked deficiency of beta-cell function. A defect of either glucose resistance or insulin resistance affecting both periphery and liver allowed a wider range of basal glucose and insulin concentration values, but resulted in unphysiologically low hepatic glucose output: with modeling insulin resistance, hyperglycemia suppressed glucose output, whereas with glucose resistance, raised insulin levels suppressed hepatic glucose output. A wide range of glucose and insulin values, with appropriate basal hepatic glucose output, could only be modeled by insulin resistance at both the liver and periphery with additional glucose resistance at the liver. The modeling results are in accord with investigative studies that suggest secondary hepatic and peripheral glucose resistance in response to hyperglycemia. Modeling provides a systematic means of examining the likely effect of different putative defects in a complex physiological system.
正常葡萄糖/胰岛素稳态的数学模型是基于肝脏和外周对不同葡萄糖/胰岛素浓度已知的实验测定反应建立的。将不同的葡萄糖抵抗和胰岛素抵抗缺陷应用于该模型，以研究这些异常能够成功预测正常、肥胖和糖尿病受试者空腹血糖和胰岛素值范围的程度。仅在肝脏或外周模拟葡萄糖抵抗或胰岛素抵抗，即使伴有明显的β细胞功能缺陷，也不会使血浆葡萄糖升高到糖尿病患者观察到的水平。影响外周和肝脏的葡萄糖抵抗或胰岛素抵抗缺陷会使基础葡萄糖和胰岛素浓度值范围更广，但会导致肝脏葡萄糖输出量低至非生理水平：模拟胰岛素抵抗时，高血糖会抑制葡萄糖输出，而模拟葡萄糖抵抗时，升高的胰岛素水平会抑制肝脏葡萄糖输出。只有在肝脏和外周均存在胰岛素抵抗且肝脏存在额外的葡萄糖抵抗时，才能模拟出具有适当基础肝脏葡萄糖输出的广泛葡萄糖和胰岛素值范围。建模结果与研究相符，这些研究表明高血糖会引发继发性肝脏和外周葡萄糖抵抗。建模提供了一种系统方法，用于研究复杂生理系统中不同假定缺陷可能产生的影响。
