Archives for December 2012

12/28/2012

Diabetes. 2012 Dec 28
Stimulation of Autophagy Improves Endoplasmic Reticulum Stress-Induced Diabetes.
Bachar-Wikstrom E, Wikstrom JD, Ariav Y, Tirosh B, Kaiser N, Cerasi E, Leibowitz G.

Source:
Endocrinology and Metabolism Service, Department of Medicine, Hadassah Medical Center, Jerusalem, Israel.

Abstract:

Accumulation of misfolded proinsulin in the β-cell leads to dysfunction induced by endoplasmic reticulum (ER) stress, with diabetes as a consequence. Autophagy helps cellular adaptation to stress via clearance of misfolded proteins and damaged organelles. We studied the effects of proinsulin misfolding on autophagy and the impact of stimulating autophagy on diabetes progression in Akita mice, which carry a mutation in proinsulin, leading to its severe misfolding. Treatment of female diabetic Akita mice with rapamycin improved diabetes, increased pancreatic insulin content, and prevented β-cell apoptosis. In vitro, autophagic flux was increased in Akita β-cells. Treatment with rapamycin further stimulated autophagy, evidenced by increased autophagosome formation and enhancement of autophagosome-lysosome fusion. This was associated with attenuation of cellular stress and apoptosis.