The Role of Beta Cell Stress in the T1D Autoimmune Process

Pancreatic beta cells are specialized cells. When stimulated, beta cells have the capacity to increase production of insulin to regulate blood glucose levels. Insulin production takes place in a specialized “factory” site within the beta cell. Increased workload in the “factory” activates a stress response in the cell which, if left unresolved, will ultimately result in dysfunction and death of the cell. The importance of the “factory” and a related stress response in the development of type 2 diabetes has been appreciated for some time, but recent evidence suggests that stress in this “factory” site is also critical in the development of T1D, both in the decline in beta cell function in response to the autoimmune attack as well as initiating or exacerbating the immune attack on the beta cell. Dr. Eizirik and his colleagues summarize a growing body of information that has been emerging over the past year and describe a theory based on this information in which “factory” stress in the beta cells at the earliest stages of T1D development create an inflammatory environment in the islet that enables or exacerbates the development of autoimmunity and progression to clinical T1D. As predicted by their theory, agents that reduce beta cell stress have been shown to prevent or delay development of T1D in animal models and may help explain the parallel rise seen in childhood obesity, metabolic dysfunction, and T1D.

Ramifications for Individuals with T1D:
This review summarizes a major shift that is occurring in our understanding about how T1D is triggered and develops. Efforts to restore and maintain normal beta cell health and function in early stages of T1D could be effective at delaying or preventing T1D development. While it is possible that this could be accomplished through the use of drugs developed for other indications, success in these efforts will likely require the development of novel drugs specifically designed to prevent beta cell stress caused by increased needs to produce insulin.

JDRF Involvement:
Much of the research described in this review was supported by JDRF.

Investigators and Institutions:
This review summarizes work from several investigators including Dr. Eizirik at the Universite Libre Bruxelles, Dr. Mirmira at Indiana University, Dr. Hotamisligil at Harvard University, Dr. Urano at Washington University, Dr. Papa at UCSF and others.

Reference:
Reviewed in: Eizirik, DL, Miani, M and Cardozo, AK (2013) Signaling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation, Diabetologia. Feb;56(2):234-41. doi: 10.1007/s00125-012-2762-3. Epub 2012 Nov 7.