title: [Treatment of type 1 diabetics by transplantation of isolated pancreatic islets].
abstract: Type 1 diabetes is an autoimmune disease with selective destruction of insulin-producing pancreatic beta cells. Since insulin plays pivotal roles in energy homeostasis by transferring glucose into cells, type 1 diabetic patients can not survive without insulin replacement. Insulin secretion is precisely controlled by ingested glucose as well as hormones and neural factors, therefore it is impossible to reproduce the physiological secretory pattern of insulin via exogenous insulin, even by multiple or continuous delivery by injection. Transplantation of beta cells has long been expected as the fundamental treatment to cure type 1 diabetics, and transplantation of the whole pancreas, both exocrine pancreas and islets, has been applied with success, resulting insulin independence. However, the exocrine pancreas, which releases amylase and trypsin to the digestive tract, is not indispensable for insulin replacement, so the interest in islet transplantation has increased enormously. In the past 20 years, the techniques for isolating large numbers of human islets have been advanced and more potent immunosuppressive agents have also been introduced, permitting newer attempts at islet transplantation. In 2000, insulin independence was first achieved in Canada using the Edmonton protocol. The success rates have increased gradually using this protocol, and 5 institutes in Japan have started to prepare human islet transplantation under the control of the Japan Pancreas and Islet Transplant Society. In 2004, insulin independence by islet transplantation was first achieved at Kyoto University Hospital and the number of islet transplantations has increased, though very slowly. By the end of 2005, approximately 100 patients were on the waiting list for islet transplantation in Japan. Many problems remain unsolved in islet transplantation to meet clinical practice: these are the shortage of insulin-producing cells, further progress in immunosuppressive agents that do not interfere with insulin secretion, strategies for protecting islets against hypoxia, and/or non-immunological damage such as mechanical damage soon after transplantation, and the destruction of islet cells by innate immunity. We investigated the role of neutrophil leucocytes infiltrating the liver using natural killer cell-knock-out mice and proposed a new strategy for protecting transplanted islets from non-specific damage, which occurs within one day after transplantation.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Fukuoka University, Fukuoka 814-0180.
authors.forename: Junko
authors.initials: J
authors.lastname: Ono
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D006801:Humans; D016381:Islets of Langerhans Transplantation