H.- S. Jun and J.- W. Yoon Pages 249 - 262 ( 14 )
Type 1 diabetes results from insulin deficiency caused by autoimmune destruction of insulin-producing pancreatic β cells. Islet transplantation, β 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 β cells from embryonic or adult stem cells may overcome the limited source of islets and transplant rejection if β cells are regenerated from endogenous stem cells. However, it is difficult to overcome the persisting hostile β cell-specific autoimmune response that may destroy the regenerated β cells. Insulin gene therapy might overcome the weakness of islet transplantation and β cell regeneration with respect to their vulnerability to autoimmune attack. This method replaces the function of β cells by introducing various components of the insulin synthetic and secretory machinery into non- β cells, which are not targets of β 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.
type 1 diabetes, islet transplantation, regeneration, embryonic stem cells, adult stem cells, specific autoimmunity, insulin gene therapy
Rosalind Franklin Comprehensive Diabetes Center, The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL, 60064, USA.