Abstract

Type 1 diabetes results from insulin deficiency caused by autoimmune destruction of insulin-producing pancreatic beta cells. Islet transplantation, beta cell regeneration, and insulin gene therapy have been explored in an attempt to cure type 1 diabetes. Major progress on islet transplantation includes substantial improvements in islet isolation technology to obtain viable and functionally intact islets and less toxic immunosuppressive drug regimes to prevent islet graft failure. However, the availability of human islets from cadaveric pancreata is limited. Regeneration of pancreatic beta cells from embryonic or adult stem cells may overcome the limited source of islets and transplant rejection if beta cells are regenerated from endogenous stem cells. However, it is difficult to overcome the persisting hostile beta cell-specific autoimmune response that may destroy the regenerated beta cells. Insulin gene therapy might overcome the weakness of islet transplantation and beta cell regeneration with respect to their vulnerability to autoimmune attack. This method replaces the function of beta cells by introducing various components of the insulin synthetic and secretory machinery into non- beta cells, which are not targets of beta cell-specific autoimmune responses. However, there is no regulatory system that results in the expression and release of insulin in response to glucose with satisfactory kinetics. Although there is no perfect solution for the cure of type 1 diabetes at the present time, research on a variety of potential approaches will offer the best choices for the cure of human type 1 diabetes.

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