Insulin granule trafficking in β-cells:: mathematical model of glucose-induced insulin secretion
Insulin granule trafficking in β-cells:: mathematical model of glucose-induced insulin secretion
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DOI：
10.1152/ajpendo.00647.2006
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发表时间：
2007-07-01
影响因子：
5.1
通讯作者：
Mingrone, Geltrude
中科院分区：
文献类型：
--
作者：
Bertuzzi, Alessandro;Salinari, Serenella;Mingrone, Geltrude
提出了一个数学模型，代表在P-细胞的细胞内胰岛素颗粒的动力学。颗粒易位和胞吐作用的控制信号被认为是基本上相关的ATP-ADP的比例和胞质，Ca 2+浓度。该模型提供了葡萄糖刺激的胰岛素分泌的触发和放大途径的作用的解释。大多数的模型参数的值推断从现有的实验数据。数值模拟代表了各种实验条件下，如高K+和细胞外葡萄糖的不同时间过程的刺激，预测的响应与已发表的实验数据一致。还测试了模型表示高血糖钳夹中测量的数据的能力。模型参数的变化，可能反映了在2型糖尿病中存在的P-细胞功能的改变进行了研究，并结合磺酰脲类受体的药理学药物的作用进行了模拟。
A mathematical model that represents the dynamics of intraceflular insulin granules in P-cells is proposed. Granule translocation and exocytosis are controlled by signals assumed to be essentially related to ATP-to-ADP ratio and cytosolic, Ca2+ concentration. The model provides an interpretation of the roles of the triggering and amplifying pathways of glucose-stimulated insulin secretion. Values of most of the model parameters were inferred from available experimental data. The numerical simulations represent a variety of experimental conditions, such as the stimulation by high K+ and by different time courses of extracellular glucose, and the predicted responses agree with published experimental data. Model capacity to represent data measured in a hyperglycemic clamp was also tested. Model parameter changes that may reflect alterations of P-cell function present in type 2 diabetes are investigated, and the action of pharmacological agents that bind to sulfonylurea receptors is simulated.