Archives for February 2013


Autophagy. 2013 Feb 4 ; 9(4)
Improvement of ER stress-induced diabetes by stimulating autophagy.
Bachar-Wikstrom E, Wikstrom JD, Kaiser N, Cerasi E, Leibowitz G.

Endocrinology and Metabolism Service; Department of Medicine; Hadassah-Hebrew University Medical Center; Jerusalem, Israel.


Pancreatic β-cell dysfunction is central in diabetes. The diabetic milieu may impair proinsulin folding, leading to β-cell endoplasmic reticulum (ER) stress and apoptosis, and thus a worsening of the diabetes. Autophagy is crucial for the well-being of the β-cell; however, the impact of stimulating autophagy on β-cell adaptation to ER stress is unknown. We studied the crosstalk between ER stress and autophagy in a rodent model of diabetes, called Akita, in which proinsulin gene mutation leads to protein misfolding and β-cell demise. We found that proinsulin misfolding stimulates autophagy and, in symmetry, inhibition of autophagy induces β-cell stress and apoptosis. Under conditions of excessive proinsulin misfolding, stimulation of autophagy by inhibiting MTORC1 alleviates stress and prevents apoptosis. Moreover,