Importance of Insulin Secretion Based on the Rate of Change in Blood Glucose Concentration in Glucose Tolerance, Assessed by the Artificial Beta Cell

Abstract

The dynamic property of glucose-induced insulin secretion was simulated with the aid of a control theory, and the relationship between the stepwise input of glucose concentration and the biphasic response of insulin as an output was expressed in the transfer function of proportional plus derivative action to glucose concentration. By utilizing this model, the following computer algorithm for the artificial beta cell was made; rate of insulin infusion = Kp BG + Kd ΔBG+ Kc, where BG was the abbreviation for glucose concentration, ΔBG was the rate of change in BG, Kp and Kd were the coefficient for the proportional and derivative action, respectively, and Kc the constant for basal insulin secretion. Microcomputer, insulin pump and digital printer were packed in small case, which was connected with glucose analyzer. Experiments were carried out in the depancreatized dogs to validate the importance of infused insulin based on derivative action to glucose concentration in glucose regulation. Kd/Kp ratio was changed when insulin was infused following iv glucose bolus injection. The results revealed that when the derivative action was added to the proportional action properly in insulin infusion regulatory system, insulin requirement was the smallest and glucose regulation was the best. The characteristics of the system recognized in clinical application were 1) rate of insulin infusion was small enough to keep the plasma concentration of insulin at a physiological level, then insulin requirements were reduced to around a half of those given subcutaneously, 2) glucose or glucagon to restore hypoglycaemia was not essential.

Pattern of insulin delivery after intravenous glucose injection in man and its relation to plasma glucose disappearance.

“…However, because in our observations in no case did we obtain negative values for insulin release, we adopted a simpler equation, with fewer parameters to be adjusted. Of note is that the mean ratio of the derivative to the proportional part, found in our subjects, Insulin Delivery after Intravenous Glucose is in agreement with the in vivo data of Kawamori et al (39). These investigators performed ivGTT in depancreatized dogs in which insulin was replaced by means of an artificial ,-cell with an algorithm similar to ours.…”

Recent Trends in Blood Glucose Control Studies

“…Blood glucose control systems have been studied since 1970s [11,[22][23][24][25][26], and some of them were clinically applied or commercially supplied. However, no system has sufficient performance for blood glucose management of diabetics.…”

The Artificial Pancreas: How Sweet Engineering Will Solve Bitter Problems

“…Shichiri and colleagues reported the development of a prototype artificial beta cell in the late 1970's. [73][74][75][76] This system was later the basis for a commercial bedside closed-loop research system, the STG-22 (Nikkiso Ltd., Tokyo, Japan), which is still being manufactured. Both devices were designed to sample blood from and deliver insulin into the intravenous space.…”

“…They have delivered insulin subcutaneously and intraperitoneally with a PD controller. 6,9,[73][74][75][76] Their results, however, were not replicated by an English group that used the same control method.…”