Deregulation of pancreas-specific oxidoreductin ERO1ß in the pathogenesis of diabetes mellitus.
Mol Cell Biol
; 34(7): 1290-9, 2014 Apr.
Article
in En
| MEDLINE
| ID: mdl-24469402
ABSTRACT
A growing body of evidence has underlined the significance of endoplasmic reticulum (ER) stress in the pathogenesis of diabetes mellitus. ER oxidoreductin 1ß (ERO1ß) is a pancreas-specific disulfide oxidase that is known to be upregulated in response to ER stress and to promote protein folding in pancreatic ß cells. It has recently been demonstrated that ERO1ß promotes insulin biogenesis in ß cells and thus contributes to physiological glucose homeostasis, though it is unknown if ERO1ß is involved in the pathogenesis of diabetes mellitus. Here we show that in diabetic model mice, ERO1ß expression is paradoxically decreased in ß cells despite the indications of increased ER stress. However, overexpression of ERO1ß in ß cells led to the upregulation of unfolded protein response genes and markedly enlarged ER lumens, indicating that ERO1ß overexpression caused ER stress in the ß cells. Insulin contents were decreased in the ß cells that overexpressed ERO1ß, leading to impaired insulin secretion in response to glucose stimulation. These data indicate the importance of the fine-tuning of the ER redox state, the disturbance of which would compromise the function of ß cells in insulin synthesis and thus contribute to the pathogenesis of diabetes mellitus.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycoproteins
/
Diabetes Mellitus, Experimental
/
Insulin-Secreting Cells
/
Endoplasmic Reticulum Stress
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell Biol
Year:
2014
Type:
Article
Affiliation country:
Japan