Autoimmune Nature of Type I Diabetes Mellitus

Abstract

Type 1 diabetes Mellitus (T1DM) is a chronic autoimmune disease in which pancreatic β‐cell destruction results in loss of endogenous insulin production. Already one of the most prevalent chronic childhood diseases, the incidence of T1DM in children and young adults is projected to continue to increase over the next several decades. Although advances in technology have allowed for improved glucose monitoring and insulin delivery, no curative therapy is currently available for this growing patient population. Moreover, patients continue to experience long‐term complications such as blindness and kidney failure, even with the most intensive insulin regimens currently available.T1DM predominantly originates when insulin‐producing beta (β)‐cells in the pancreas are destroyed or suppressed due to an autoimmune response caused by the auto‐reactive T‐helper 1 (Th1) cells. Interestingly, the antigens responsible for this immune response, glutamic acid decarboxylase, are normally present in β‐cells; however, their destructive capabilities are restrained by the regulatory mechanisms of the body. When a person has certain genetic factors (e.g. the absence of certain protective histocompatibility locus antigen) and exposure to certain environmental factors, they are predisposed to immunologic injury of β‐cells. Furthermore, the odds of presenting with T1DM diminish with treatment with immune‐suppressive regimens that specifically target T‐cells. As a result, Th1 cells dominate the protective regulatory T‐cells. In turn, Th1 cells secrete cytokines, interleukin 2, and interferon gamma, which initiate inflammation of the islet cells that appears to result in the development of T1DM.In 2001 it was found that diabetes might be the first disease for which stem cell therapy is an option, when insulin‐producing embryonic stem cells of R1‐mice were transplanted into streptozotocin‐induced diabetic animals and normal blood glucose levels were achieved, and in other studies implantation of embryonic Sertoli cells into diabetic db mice also resulted in amelioration of the diabetic state. In contrast, infusion of cord blood derived stem cells in the absence of immunomodulation was without lasting effect on the diabetic state. Minor complications in R1‐mice aside, this event once again renewed the quest to find more practical and functional means to create human islets to treat diabetes.Can pancreatic stem cell transplant be used as a cure for T1DM, an autoimmune disease, and how does it stand against other cell transplants and other treatment modalities in the US? The bulk of preliminary evidence to date suggests encouraging potential for such approaches in the treatment of T1DM.Support or Funding InformationSupported by Institutional Resources of USAT, the Einstein Institute, and the University of Massassachusetts.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.