Dysfunctional autophagy following exposure to pro-inflammatory cytokines contributes to pancreatic β-cell apoptosis.

ABSTRACT: Type 1 diabetes (T1D) results from β-cell destruction due to concerted action of both innate and adaptive immune responses. Pro-inflammatory cytokines, such as interleukin-1β and interferon-γ, secreted by the immune cells invading islets of Langerhans, contribute to pancreatic β-cell death in T1D. Cytokine-induced endoplasmic reticulum (ER) stress plays a central role in β-cell demise. ER stress can modulate autophagic response; however, no study addressed the regulation of autophagy during the pathophysiology of T1D. In this study, we document that cytokines activate the AMPK-ULK-1 pathway while inhibiting mTORC1, which stimulates autophagy activity in an ER stress-dependent manner. On the other hand, time-course analysis of LC3-II accumulation in autophagosomes revealed that cytokines bl

SUBMITTER: Lambelet M 

PROVIDER: S-EPMC5833699 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature