Basic study in artificial pancreas using encapsulated islets as blood glucose measurement and control system

人工胰腺(人工β细胞)分为两类，即使用机械胰岛素输注泵的机械人工胰腺和使用包膜胰岛的生物人工(杂交)胰腺。机械人工胰腺被细分为使用葡萄糖传感系统的闭环控制系统和不使用葡萄糖传感系统的开环系统。在机械人工胰腺的情况下，开环控制系统按照预先编程的模式输入胰岛素而不感知血糖，不能很好地控制血糖水平。虽然闭环系统可以根据患者血糖水平的测量结果，通过注入适量的胰岛素来很好地控制血糖水平，但目前可用的植入式血糖传感器的寿命限制了连续使用的时间。此外，传感器的漂移可能会导致控制品质的恶化。另一方面，生物人工(混合)胰腺使用从动物(如猪)采集的活的朗格汉斯胰岛来控制和测量患者的血糖水平。然而，为了将这种方法应用于人类，所需的胰岛数量很大。植入包膜后的胰岛在体内蓄积，可能对长期使用造成危害。在这项研究中，我们提出了一种新型的人工胰腺，其中开环机械人工胰腺按照预先编程的模式提供所需的大部分胰岛素，而封装的朗格汉斯胰岛作为一个测量和控制系统来处理开环系统无法控制的剩余误差。计算机模拟研究和初步动物实验证实了该新系统的可行性。

Artificial pancreas (artificial βcell) is divided into two categories, namely mechanical artificial pancreas which uses mechanical insulin infusion pump, and bio-artificial (hybrid) pancreas using encapsulated islets of Langerhans. Mechanical artificial pancreas is subdivided into a closed loop control system that uses glucose sensing system and an open loop system that does not use glucose sensing system. In case of mechanical artificial pancreas, open loop control system that infuses insulin according to pre-programmed pattern without glucose sensing does not provide good control of blood glucose level. Although the closed loop system can control blood glucose level well by infusing appropriate amount of insulin based on the measurement of the patient's glucose level, the longevity of the currently available implantable glucose sensor limits the duration of continuous usage. Also the drift of the sensor might lead to the deterioration of control quality. On the other hand, bio-artificial (hybrid) pancreas uses living islet of Langerhans harvested from an animal such as pig for control and measurement of blood glucose level of a patient. However, in order to apply this method to human, amount of required islet is very large. The accumulation of implanted encapsulated islet in body might do harm in long term application. In this study, we proposed a novel artificial pancreas where open loop mechanical artificial pancreas provides most of the insulin required in accordance with the pre-programmed pattern and encapsulated islet of Langerhans function as a measurement and control system for the remaining errors that cannot be controlled by the open loop system. The feasibility of this new system was confirmed by computer simulation study and preliminary animal experiment.