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 .DELTA.BG + Kc, where BG was the abbreviation for glucose concentration, .DELTA.BG was the rate of change in BG, Kp and Kd were the coefficient for the proportional and derivative action, respectively, and Kd the constant for basal insulin secretion. The microcomputer, insulin pump and digital printer were packed in a small case, which was connected with the glucose analyzer. Experiments were carried out in depancreatized dogs and the Kd/Kp ratio was changed when insulin was infused following i.v. glucose bolus injection. When the derivative action was added to the proportional action properly in an insulin infusion regulatory system, the insulin requirement was the smallest and glucose regulation was the best. The characteristics of the system in clinical application [humans] were recognized. The rate of insulin infusion was small enough to keep the plasma concentration of insulin at a physiological level, and insulin requirements were reduced to around a half of those given s.c. Glucose or glucagon to restore hypoglycemia was not necessary.