β-Cell autophagy in the pathogenesis of type 1 diabetes

Abstract

Type 1 diabetes is an insulin-dependent, autoimmune disease where the pancreatic β cells are destroyed resulting in hyperglycemia. This multifactorial disease involves multiple environmental and genetic factors, and has no clear etiology. Accumulating evidence suggests that early signaling defects within the β cells may promote a change in the local immune milieu leading to autoimmunity. Therefore, many studies have been focused on intrinsic β-cell mechanisms that aid in the restoration of cellular homeostasis under environmental conditions that cause dysfunction. One of these intrinsic mechanisms to promote homeostasis is autophagy, defects which are clearly linked with β-cell dysfunction in the context of type 2 diabetes. Recent studies have now also pointed towards β-cell autophagy defects in the context of type 1 diabetes. In this perspectives review, we will discuss the evidence supporting a role for β-cell autophagy in the pathogenesis of type 1 diabetes, including a potential role for unconventional secretion of autophagosomes/lysosomes in the changing dialogue between the β cell and immune cells.