Type 1 diabetes (T1D) is a chronic inflammatory disease that is characterized by autoimmune destruction of
insulin-producing pancreatic beta cells. The goal of this study was to identify novel
protein signatures that distinguish Islets from patients with T1D, patients who are
autoantibody positive without symptoms of diabetes, and from individuals with no evidence of disease. High resolution high mass accuracy label free quantitative mass spectrometry analysis was applied to islets isolated by
laser capture microdissection from disease stratified human pancreata from the Network for Pancreatic Organ Donors with Diabetes (nPOD), these included donors without diabetes, donors with T1D-associated
autoantibodies in the absence of diabetes, and donors with T1D. Thirty-nine
proteins were found to be differentially regulated in
autoantibody positive cases compared to the no-disease group, with 25 upregulated and 14 downregulated
proteins. For the T1D cases, 63
proteins were differentially expressed, with 24 upregulated and 39 downregulated, compared to the no disease controls. We have identified functional annotated enriched gene families and multiple
protein-
protein interaction clusters of
proteins are involved in biological and molecular processes that may have a role in T1D. The
proteins that are upregulated in T1D cases include S100A9, S100A8, REG1B, REG3A and C9 amongst others. These
proteins have important biological functions, such as
inflammation, metabolic regulation, and autoimmunity, all of which are pathways linked to the pathogenesis of T1D. The identified
proteins may be involved in T1D development and pathogenesis. Our findings of novel
proteins uniquely upregulated in T1D pancreas provides impetus for further investigations focusing on their expression profiles in beta cells/ islets to evaluate their role in the disease pathogenesis. Some of these molecules may be novel therapeutic targets T1D.