252-LB: Insulin Secretion Pathway Genes Correlate with Markers Associated with Viral Infections in Human Islets

Type 1 diabetes (T1D) is an autoimmune disease hypothesized, to be enhanced or triggered by viral infections. In this study we used organ donor pancreas to isolate islets that expressed known signs of viral infections, and subsequently investigated pathways that may be secondarily affected through analysis of gene expression profiles. Using samples provided by the Network for Pancreatic Organ Donors with Diabetes, (nPOD), islets were collected, by laser-capture, from nondiabetic donors (Control), autoantibody positive nondiabetic donors (AB+) and donors with T1D (T1D). Islets were categorized based on the presence of markers associated with viral infection (VIMs), HLA, Mx1, dsRNA, and PKR, identified via immunohistochemical staining. From each donor islets were pooled based on the number of VIMs (0 VIMs, 1 VIMs or ≥2VIMs). RNA was extracted, and microarray used to assess transcriptomes. GeneSpring software was used to generate a list of genes with differential expression between donors/VIMs. Using WebGestalt we identified pathways enriched by this list. A total of 383 genes with a fold change of ≥1.1 and p-value=0.001 had differential expression between islets with 0 VIMs and ≥1 VIMs. Pathway analysis showed strongest enrichment for genes in the insulin secretion pathway (p Disclosure G. Nelson: None. N.I. Lenchik: None. T. Rodriguez-Calvo: None. D. Balcacean: None. I.C. Gerling: None. Funding JDRF; National Institute of Diabetes and Digestive and Kidney Diseases; Lebonheur Children’s Hospital