Guyton J R, Foster R O, Soeldner J S, Tan M H, Kahn C B, Koncz L, Gleason R E
Diabetes. 1978 Oct;27(10):1027-42. doi: 10.2337/diab.27.10.1027.
Current physiologic knowledge about glucose-insulin homeostasis in liver, brain, pancreas, kidney, peripheral tissues, and central vascular organs has been synthesized to form a whole-system mathematical model of glucose metabolism in normal, ideal man. In addition to data of other workers, results from more than 100 intravenous glucose tolerance tests, including variable dosage, variable duration of infusion, and double pulse studies, were used to determine model structure and parameters. Model and clinical testing have focused particularly on the fast phase of insulin response to vascular glucose. The model incorporates blood circulation and equilibration of substances between vascular and interstitial spaces, and it assumes constant fractional clearance of insulin by liver and kidney. Studies using a double pulse of glucose suggest that the time derivative of glucose level is not the sole or predominant influence on fast phase insulin release, but that preinfusion glucose level and/or previous glucose exposure of the pancreas are also important. Variable dosage glucose studies suggest that the amount of insulin released during the fast phase rather than the insulin release rate is regulated by the glucose level. A two-pool, heterogeneous threshold mechanism for beta cell response to glucose is presented that is compatible with the clinical results.
目前关于肝脏、大脑、胰腺、肾脏、外周组织和中枢血管器官中葡萄糖-胰岛素稳态的生理学知识已被整合，以形成一个正常理想人体葡萄糖代谢的全系统数学模型。除了其他研究人员的数据外，还使用了100多次静脉葡萄糖耐量试验的结果，包括不同剂量、不同输注持续时间和双脉冲研究，来确定模型结构和参数。模型和临床测试特别关注胰岛素对血管葡萄糖反应的快速阶段。该模型纳入了血液循环以及血管和间质空间之间物质的平衡，并假设肝脏和肾脏对胰岛素的清除率恒定。使用双脉冲葡萄糖的研究表明，葡萄糖水平的时间导数不是快速阶段胰岛素释放的唯一或主要影响因素，而是输注前的葡萄糖水平和/或胰腺先前的葡萄糖暴露也很重要。不同剂量葡萄糖研究表明，快速阶段释放的胰岛素量而非胰岛素释放速率受葡萄糖水平调节。提出了一种与临床结果相符的β细胞对葡萄糖反应的双池、异质性阈值机制。
