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Autophagy plays a protective role in endoplasmic reticulum stress-mediated pancreatic ? cell death.


ABSTRACT: There is a growing evidence of the role of autophagy in pancreatic ? cell homeostasis. During development of type 2 diabetes, ? cells are required to supply the increased demand of insulin. In such a stage, ? cells have to address high ER stress conditions that could lead to abnormal insulin secretion, and ultimately, ? cell death and overt diabetes. In this study, we used insulin secretion-deficient ? cells derived from fetal mice. These cells present an increased accumulation of polyubiquitinated protein aggregates and LC3B-positive puncta, when compared with insulinoma-derived ? cell lines. We found that insulin secretion deficiency renders these cells hypersensitive to endoplasmic reticulum (ER) stress-mediated cell death. Chemical or shRNA-mediated inhibition of autophagy increased ? cell death under ER stress. On the other hand, rapamycin treatment increased both autophagy and cell survival under ER stress. Insulin secretion-deficient ? cells showed a marked reduction of the antiapoptotic protein BCL2, together with increased BAX expression and ERN1 hyperactivation upon ER stress induction. These results showed how insulin secretion deficiency in ? cells may be contributing to ER stress-mediated cell death, and in this regard, we showed how the autophagic response plays a prosurvival role.

SUBMITTER: Bartolome A 

PROVIDER: S-EPMC3541286 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Autophagy plays a protective role in endoplasmic reticulum stress-mediated pancreatic β cell death.

Bartolome Alberto A   Guillen Carlos C   Guillen Carlos C   Benito Manuel M  

Autophagy 20120905 12


There is a growing evidence of the role of autophagy in pancreatic β cell homeostasis. During development of type 2 diabetes, β cells are required to supply the increased demand of insulin. In such a stage, β cells have to address high ER stress conditions that could lead to abnormal insulin secretion, and ultimately, β cell death and overt diabetes. In this study, we used insulin secretion-deficient β cells derived from fetal mice. These cells present an increased accumulation of polyubiquitina  ...[more]

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