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- PLIN2 is a Key Regulator of the Unfolded Protein Response and Endoplasmic Reticulum Stress Resolution in Pancreatic β Cells.
PLIN2 is a Key Regulator of the Unfolded Protein Response and Endoplasmic Reticulum Stress Resolution in Pancreatic β Cells.
Citation | “Plin2 Is A Key Regulator Of The Unfolded Protein Response And Endoplasmic Reticulum Stress Resolution In Pancreatic Β Cells.”. Scientific Reports, p. 40855. . |
Author | Elaine Chen, Tsung Huang Tsai, Lan Li, Pradip Saha, Lawrence Chan, Benny Hung-Junn Chang |
Abstract |
Progressive pancreatic β cell failure underlies the transition of impaired glucose tolerance to overt diabetes; endoplasmic reticulum (ER) stress expedites β cell failure in this situation. ER stress can be elicited by lipotoxicity and an increased demand for insulin in diabetes. We previously reported that the lipid droplet protein perilipin 2 (PLIN2) modulates lipid homeostasis in the liver. Here, we show that PLIN2 modulates the unfolded protein response (UPR) and ER stress in pancreatic β cells. PLIN2 expression goes up when β cells are exposed to a lipid load or to chemical ER stress inducers. Downregulation of PLIN2 ameliorates the effects of fatty acid- and chemical-induced ER stress, whereas PLIN2 overexpression exacerbates them. Diabetic Akita mice, which carry a heterozygous C96Y Ins2 mutation, exhibit elevated PLIN2 expression and ER stress in their β cells. Genetic ablation of Plin2 in Akita mice leads to mitigation of ER stress, forestalling β cell apoptosis, partially restoring β cell mass, and ameliorating diabetes. Mechanistic experiments showed that PLIN2 downregulation is associated with enhanced autophagic flux and accelerated ER stress resolution. In sum, we have identified a crucial role for PLIN2 in modulating autophagy, ER stress resolution, and β cell apoptosis and survival. |
Year of Publication |
2017
|
Journal |
Scientific reports
|
Volume |
7
|
Number of Pages |
40855
|
Date Published |
12/2017
|
ISSN Number |
2045-2322
|
DOI |
10.1038/srep40855
|
Alternate Journal |
Sci Rep
|
PMID |
28102311
|
PMCID |
PMC5244387
|
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