An ideal implantable artificial pancreas would deliver insulin to a diabetic patient in response to the patient's blood glucose level. This would provide closed-loop control of glycemia, and would mimic the endocrine action of the normal, nondiabetic pancreas. Such a devise might prevent many of the long term complications of diabetes, e.g. atherosclerosis, nephropathy and blindness. We propose to test the feasibility of a self-regulating osmotic insulin pump, whose rate of insulin release depends on blood glucose concentration. The regulation of insulin output is determined by a novel membrane whose permeability to water is glucose- dependent. The synthesis of such a membrane is the primary focus of the proposal. The membrane will consist of two lamina. The first lamina converts glucose to gluconic acid, and the second lamina is a polymer that swells in the presence of gluconic acid, increasing its water permeability. We will determine the polymer properties that are necessary for rapid changes in permeability given changes in pH, and ultimately glucose concentration. Once having optimized the membrane, we will include it in a prototype osmotic pump. We will test the pump in vitro to determine whether self-regulated osmotic pumping is a feasible means of controlling glycemia. We believe that this approach will obviate certain design problems associated with devices, proposed by other researchers, that depend on membranes whose permeability to insulin is modulated by blood glucose levels.
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