**Author details**

Morihito Takita1 , Nigar Seven1 , Marlon F. Levy2 and Bashoo Naziruddin2\*

\*Address all correspondence to: BashooN@Baylorhealth.edu

1 Baylor Research Institute, Islet Cell Laboratory, Dallas, USA

2 Baylor Simmons Transplant Institute, Dallas, USA

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**Chapter 8**

**Endoplasmic Reticulum (ER) Stress in the Pathogenesis**

As one of the major health problems in the world, diabetes affects over 346 million people worldwide. In United States alone, according to the statistical fact sheet released 2011 by American Diabetes Association, 25.8 million children and adults accounting for 8.3% of the population are affected by diabetes. Unfortunately, the therapy of diabetes remains unsatis‐ fied despite of extensive studies in the last decades. Diabetes can be categorized into two main types: type 1 and type 2. Type 1 diabetes mellitus, used to known as juvenile diabetes, is typically developed in children and juveniles. Despite the increasing rate of Type 2 diabe‐ tes in the United States, type 1 diabetes accounts for over 2/3 of new adolescent diabetes di‐ agnoses. Although most commonly presented in childhood, type 1 diabetes also accounts for 5-10% cases of adult diabetes (1). Recent epidemiologic studies revealed that the inci‐

Unlike type 2 diabetes, which is caused by the loss of insulin sensitivity, type 1 diabetes is caused by insulin deficiency following destruction of insulin-producing pancreatic β cells. Autoimmune-mediated β cell death has been considered as the major cause of βcell loss in type 1 diabetes. However, the underlying mechanisms are not fully under‐ stood. Accumulating evidence suggests an involvement of endoplasmic reticulum (ER) stress in multiple biological processes during the development of type 1 diabetes. Pancre‐ atic β cells exhibit exquisite sensitivity to ER stress due to their high development in or‐ der to secrete large amounts of insulin. There is also evidence supporting that ER stress regulates the immune cell functionality and cytokine production that is relevant to auto‐ immune processes in type 1 diabetes. Furthermore, β cell loss caused by autoimmune at‐ tack results in an increased ER burden on the rest pancreatic β cells and induces unfolded protein response (UPR) and ER stress, which further exacerbates β cell death. Here I will

> © 2013 Zhong; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

dence for type 1 diabetes in most regions of the world has increased by 2-5% (2).

**of Type 1 Diabetes**

http://dx.doi.org/10.5772/52644

Additional information is available at the end of the chapter

Jixin Zhong

**1. Introduction**

