A model of β-cell mass, insulin, and glucose kinetics:: Pathways to diabetes
A model of β-cell mass, insulin, and glucose kinetics:: Pathways to diabetes
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DOI：
10.1006/jtbi.2000.2150
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发表时间：
2000-10-21
影响因子：
2
通讯作者：
Finegood, DT
中科院分区：
文献类型：
--
作者：
Topp, B;Promislow, K;Finegood, DT
糖尿病是一种血糖调节系统疾病，与发病率和早期死亡率的增加有关。该系统的主要变量是β细胞质量、血浆胰岛素浓度和血糖浓度。现有的血糖调节数学模型仅包含葡萄糖和/或胰岛素动力学。在这里，我们建立了一个新的β细胞质量、胰岛素和葡萄糖动力学模型，它由一个由三个非线性常微分方程组组成的系统组成，其中葡萄糖和胰岛素的动力学相对于β细胞质量动力学是快速的。对于正常参数值，模型有两个稳定的不动点(代表生理和病理稳定状态)，在慢流形上由鞍点隔开。轻度高血糖导致β细胞团的生长(负反馈)，而极度高血糖导致β细胞团的减少(正反馈)。该模型预测，长期高血糖有三条途径：(1)生理固定点可以移动到高血糖水平(调节性高血糖)，(2)生理和鞍点可以被消除(分叉)，(3)葡萄糖和/或胰岛素动力学的进行性缺陷可以使血糖水平以比β细胞团适应更快的速度上升，从而使血糖水平下降(动态高血糖)。(C)2000年学术出版社。
Diabetes is a disease of the glucose regulatory system that is associated with increased morbidity and early mortality. The primary variables of this system are beta -cell mass, plasma insulin concentrations, and plasma glucose concentrations. Existing mathematical models of glucose regulation incorporate only glucose and/or insulin dynamics. Here we develop a novel model of beta -cell mass, insulin, and glucose dynamics, which consists of a system of three nonlinear ordinary differential equations, where glucose and insulin dynamics are fast relative to beta -cell mass dynamics. For normal parameter values, the model has two stable fixed points (representing physiological and pathological steady states), separated on a slow manifold by a saddle point. Mild hyperglycemia leads to the growth of the beta -cell mass (negative feedback) while extreme hyperglycemia leads to the reduction of the beta -cell mass (positive feedback). The model predicts that there are three pathways in prolonged hyperglycemia: (1) the physiological fixed point can be shifted to a hyperglycemic level (regulated hyperglycemia), (2) the physiological and saddle points can be eliminated (bifurcation), and (3) progressive defects in glucose and/or insulin dynamics can drive glucose levels up at a rate faster than the adaptation of the beta -cell mass which can drive glucose levels down (dynamical hyperglycemia). (C) 2000 Academic Press.