Effect of Acute IFN-α Exposure on β-cell Survival and Function in the Absence of Functional Autophagy

Background and Hypothesis: It has been demonstrated that the protective degradative process of autophagy is defective in context human T1D. Additionally, a type I interferon-inducible transcriptional signature detected blood cells children genetically at risk for T1D prior to appearance autoantibodies. Preliminary data demonstrate can be stimulated by IFN-α β-cells non-diabetic mice, but this response nonobese diabetic (NOD) mouse model autoimmune diabetes. We hypothesize impaired exposure will lead reduced β-cell survival function.Methods:Bafilomycin A, lysosomal inhibitor, was used inhibit INS-1 832/13 pancreatic islets. then utilized western blot analysis, Caspase-Glo® 3/7 Assay, Insulin HTRF Assay assess function exposure.Results: Western analysis monitor inhibition stimulation pathway (n=4) islets (n=1). An increase LC3II/LC3I ratio observed after treatment with Baf indicating accumulation autophagosomes. Phosphorylation STAT2 treated cells, pathway. Impaired did not induce apoptosis (n=2). Following A treatment, glucose insulin secretion measured. Glucose decreased following (n=2).Conclusions: These suggest followed an acute does significant cell death, modestly impairs function. Future studies determine effects prolonged on as well investigate other potential mechanisms death.