Morphologic characteristics of insulin precipitates were examined by both scanning and transmission electron microscopy. Insulin precipitate obtained after 1 wk of in vivo storage in an implanted dog reservoir was compared with insulin precipitate produced in vitro by isoelectric precipitation, acid-freeze-heat precipitation, and motion-induced precipitation. Insulin precipitate produced in vivo had several morphologic forms, with spherical-lamellar structures predominating. In vitro isoelectric precipitated insulin produced microcrystalline material, whereas acid-freeze-heat and motion-induced precipitated insulin were associated with elongated fibrils. The morphologic appearance of the in vivo precipitated insulin was not entirely reproduced by any of the three in vitro methods of insulin precipitation. We conclude that insulin precipitation in vivo is a process that may involve more than one of the known mechanisms by which insulin precipitates in vitro.

An implantable insulin delivery system has several advantages not shared by currently available, portable external delivery devices. First, since the implantable system does not come in contact with the external environment, insulin delivery routes other than the subcutaneous tissue may be utilized without the danger of infection. These alternative routes may provide more rapid insulin absorption, enhanced hepatic insulinization, and improved diabetic control for "C"-peptide-negative brittle diabetic patients. Second, the implantable system is protected from external trauma, permitting a wider range of daily activities and sporting events. Third, the implantable system is easily concealed by clothing, thereby increasing patient acceptance of it. However, an implantable system also has disadvantages. First, surgery will be required to implant or explant the pump module and reservoir, and second, the implanted system must be highly reliable and include failsafe mechanisms to insure the safety of the recipient. These advantages and disadvantages have resulted in delineation of general specifications for an inv plantable insulin delivery system. Desirable features of an implantable insulin delivery system include (1) reliability and failsafe operation, (2) being implantable and explantable under local anesthesia, (3) long battery life, (4) multiple insulin delivery rates, (5) small size and weight, (6) biocompatible materials, (7) remote programmability based upon recipient blood glucose monitoring, and (8) ability to deliver concentrated insulin with infrequent reservoir refilling. Using available technology, each of these specifications has been incorporated into the functioning of our current implant system, which is being tested in diabetic dogs. Future experiments in man will undoubtedly alter and add to the current specifications. DIABETES CARE 4: 319-324, MARCH-APRIL, 1981.