Vacuole Membrane Protein 1 expression in beta-cells during naturally occurring diabetes in NOD mice.

ANDREONE, LUZ; ROSSI, M; ARIOLFO, LAURA; ROPOLO, ALEJANDRO; PERONE, MARCELO JAVIER; GIMENO, MARÍA LAURA; VACCARO, MI

Buenos Aires

Congreso; IAP / LAPSG Joint Meeting ? Pancreas 2017; 2017

Type 1 diabetes is an autoimmune disease in which insulin production is compromised due to dysfunction of beta-cells by means of immune cells infiltrating islets (insulitis). We found that in response to experimentally-induced diabetes the autophagy pathway was activated to regulate cellular homeostasis. VMP1 is an autophagy-related protein that was found elevated during the course of several pathologies including diabetes. Based on this observation the Aim: of this work was to determine whether VMP1 is involved in the process of beta-cell demise in the naturally progress of disease employing the non-obese diabetic (NOD) mice model of diabetes. Methods: NOD mice (4-28wk); immune-fluorescence microscopy. Results: Insulitis severity increased with age in female NOD mice while the intensity of immune-reactive insulin, assessed by IF, decreased. VMP1 co-expressed with insulin, and its expression was mainly detected in pancreatic beta-cells. Local production of inflammatory cytokines during insulitis triggers beta-cell death. Mimicking this process in vitro, we challenged the rat insulinoma INS-1E and isolated mouse islets with IL-1b+IFN-g (CYT). We detected an increase in the expression of VMP1 in both INS-1E cells and beta-cells within islets after CYT exposure resembling the findings in NOD islets. Discussion: VMP1 expression is induced by proinflammatory cytokines during the process of beta-cell apoptosis during autoimmune diabetes. Experiments are being carried out to unravel the mechanistic action of VMP1 in beta-cells under autoimmunity in diabetes.