Artificial connection between glucose sensing and insulin delivery: implications of peritoneal administration

The replacement of insulinogenic function in insulin-dependent diabetes has to restore the feedback between intracorporal glucose and insulin. This has been accomplished by the following approaches: (a) the so-called open-loop insulin treatment by means of injections or pumps, employing laboratory or other extracorporal analytical devices and closing the feedback at large intervals only; (b) transplantation of insulin producing tissue and the bioartificial pancreas, employing the natural beta-cell both for glucose sensing and insulin delivery; (c) implanted artificial drug delivery systems providing chemical feedback between intracorporal glucose and insulin release from a nonrefillable reservoir of limited capacity; (d) the intracorporal or paracorporal artificial beta-cell comprising a glucose sensor (electrochemical or other type) that permanently delivers the signal to the computer-controlled insulin pump. This artificial device works on the basis of an algorithm of glucose-dependent insulin provision, compensating for the lack of other regulators, for the site of insulin administration, which is usually posthepatic, and for the kinetic properties of sensing system, e.g., a subcutaneous inserted amperometric electrode. Present experimental studies show that the pharmacodynamics of peritoneally applied insulin may be implemented into a mathematical model of the overall glucose-insulin system. They include absorption nearly as fast as after intravenous application, predominant portal inflow and approximately 30% hepatic removal. Feedback-controlled peritoneal insulin administration by means of an artificial beta-cell working on peripheral-venous blood glucose monitoring results in normal glycemic profiles under basal conditions and during oral glucose loads, if the pharmacodynamic properties of the peritoneal route are implemented into the insulin dosage algorithm.