Autophagy and VMP1 expression are early cellular events in experimental diabetes.
OBJECTIVE
We have described VMP1 as a new protein which expression triggers autophagy in mammalian cells. Here we show that experimental diabetes activates VMP1 expression and autophagy in pancreas beta cells as a direct response to streptozotocin (STZ).


METHODS
Male Wistar rats were treated with 65 mg/kg STZ and pancreas islets from untreated rats were incubated with 1 mM STZ.


RESULTS
RT-PCR analysis shows early VMP1 induction after STZ treatment. In situ hybridization reveals VMP1 mRNA in islet beta cells. Electron microscopy shows chromatin aggregation and autophagy morphology that was confirmed by LC3 expression and LC3-VMP1 co-localization. Apoptotic cell death and the reduction of beta cell pool are evident after 24 h treatment, while VMP1 is still expressed in the remaining cells. VMP1-Beclin1 colocalization in pancreas tissue from STZ-treated rats suggests that VMP1-Beclin1 interaction is involved in the autophagic process activation during experimental diabetes. Results were confirmed using pancreas islets, showing VMP1 expression and autophagy in beta cells as a direct effect of STZ treatment.


CONCLUSIONS
Pancreas beta cells trigger VMP1 expression and autophagy during the early cellular events in response to experimental diabetes.
Grasso
Daniel
D
Department of Physiology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Sacchetti
Maria L
ML
Bruno
Lidia
L
Lo Ré
Andrea
A
Iovanna
Juan L
JL
Gonzalez
Claudio D
CD
Vaccaro
Maria I
MI
D000818:Animals; D001343:Autophagy; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015870:Gene Expression / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D008565:Membrane Proteins; C446296:VMP1 protein, rat; D013311:Streptozocin