Insulin self-regulated release

G Albin, TA Horbett, BD Ratner. Glucose-sensitive membranes for controlled release of insulin. In J Kost, ed. Pulsed and Self-Regulated Drug Delivery. Boca Raton, FL CRC Press, 1990, pp 159-185. 

Makino K, Mack EJ, Okano T, Kim SW. A microcapsule self-regulating delivery system for insulin. J Controlled Release 1990 12 235-239. 

Before we can start to develop a model we also have to decide how to interpret the behavior observed in Fig. 2.1. The variations in insulin and glucose concentrations could be generated by a damped oscillatory system that was continuously excited by external perturbations (e.g. through interaction with the pulsatile release of other hormones). However, the variations could also represent a disturbed self-sustained oscillation, or they could be an example of deterministic chaos. Here, it is important to realize that, with a sampling period of 10 min over the considered periods of 20-24 h, the number of data points are insufficient for any statistical analysis to distinguish between the possible modes. We need to make a choice and, in the present case, our choice is to consider the insulin-glucose regulation to operate... 

Figure 16.8 Self-regulated insulin release membrane made of poly(N,N -diethylaminoethyl methacrylate) hydrogel membrane. As glucose enters the membrane, glucose oxidase entrapped inside the membrane transforms glucose into gluconic acid, which in turn reduces the pH of the hydrogel membrane. This causes swelling of the membrane followed by more release of insulin through the membrane...

Further development of the self-regulating insulin delivery system has utilized the complex of glycosylated insulin-concanavalin A, which is encapsulated inside a polymer membrane. As glucose penetrates into the system, it activates the release of glycosylated insulin from the complex for a controlled release from the system (Fig. 28). The amount of insulin released is thus self-regulated by the concentration of glucose that has penetrated into the insulin delivery system. 

Self-regulated insulin device. Because replacement of insulin in diabetic patients by simple injection is not able to prevent the serious consequences of the disease [37], considerable effort is currently being devoted to the development of devices that can release insulin in response to external glucose concentration. 

Bioresponsive hydrogels can be employed to implement a self-regulating system for controlled release of insulin in response to an environmental glucose concentration. Toward this goal, Podual et al. [116] prepared a series... 

Common to all the self-regulating systems is the lack of evaluation of their in vivo performance. Critical issues in this respect include long-term stability of insulin in such hydrophobic environments and the stability and/or potential leakage and possible immunogenicity of the enzymes and other agents used in these systems. Also, the physical dimensions, response times, and reproducibility of release are pivotal questions with such systems. 

Siegel, R. A., and Firestone, B. A., 1990, Mechanochemical approaches to self-regulating insulin pump design, J. Controlled Release 11 181-192. 

The glucose-sensitivity and other interesting properties of boronic acid-containing hydrogels lead to various applications, such as glucose sensing, self-regulated insulin release, and so on. 

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