Autophagy and VMP1 Expression Are Early Cellular Events in Experimental Diabetes

GRASSO, D; SACCHETTI, ML; BRUNO, L; LO RÉ, A; IOVANNA, JL; GONZALEZ, CD; VACCARO, MI

PANCREATOLOGY

Karger

Lugar: Basel, Switzerland.; Año: 2009 vol. 9 p. 81 - 88

1424-3903

Background/Aims:  We have described VMP1 as a new pro- tein 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 m M  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 aggre- gation 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 remain- ing cells. VMP1-Beclin1 colocalization in pancreas tissue from STZ-treated rats suggests that VMP1-Beclin1 interaction is in- volved in the autophagic process activation during experi- mental diabetes. Results were confirmed using pancreas is- lets, showing VMP1 expression and autophagy in beta cells as a direct effect of STZ treatment.  Conclusion:  Pancreas beta cells trigger VMP1 expression and autophagy during the early cellular events in response to experimental diabe- tes.