title: Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes.
abstract: Type 1 diabetes (T1D) and type 2 diabetes (T2D) are associated with functional beta cell loss due to ongoing inflammation. Despite shared similarities, T1D is an autoimmune disease with evidence of autoantibody production, as well as a role for exocrine pancreas involvement. Our hypothesis is that differential protein expression occurs in disease stratified pancreas tissues and regulated proteins from endocrine and exocrine tissues are potential markers of disease and potential therapeutic targets. The study objective was to identify novel proteins that distinguish the pancreas from donors with T1D from the pancreas from patients with T2D, or autoantibody positive non-diabetic donors. Detailed quantitative comprehensive proteomic analysis was applied to snap frozen human pancreatic tissue lysates from organ donors without diabetes, with T1D-associated autoantibodies in the absence of diabetes, with T1D, or with T2D. These disease-stratified human pancreas tissues contain exocrine and endocrine tissues (with dysfunctional islets) in the same microenvironment. The expression profiles of several of the proteins were further verified by western blot. We identified protein panels that are significantly and uniquely upregulated in the three disease-stratified pancreas tissues compared to non-disease control tissues. These proteins are involved in inflammation, metabolic regulation, and autoimmunity, all of which are pathways linked to, and likely involved in, T1 and T2 diabetes pathogenesis. Several new proteins were differentially upregulated in prediabetic, T1D, and T2D pancreas. The results identify proteins that could serve as novel prognostic, diagnostic, and therapeutic tools to preserve functional islet mass in Type 1 Diabetes.
authors: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States of America; Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States of America.
authors: Tanya C
authors: TC
authors: Burch
authors: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States of America; Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, United States of America; Strelitz Diabetes Research Center, Eastern Virginia Medical School, Norfolk, VA, United States of America.
authors: Margaret A
authors: MA
authors: Morris
authors: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida Gainesville, FL, United States of America.
authors: Martha
authors: M
authors: Campbell-Thompson
authors: Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, United States of America.
authors: Alberto
authors: A
authors: Pugliese
authors: Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, United States of America; Strelitz Diabetes Research Center, Eastern Virginia Medical School, Norfolk, VA, United States of America.
authors: Jerry L
authors: JL
authors: Nadler
authors: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States of America; Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States of America.
authors: Julius O
authors: JO
authors: Nyalwidhe
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis / Q000235:genetics*; D060066:Protein Interaction Maps / Q000235:genetics; D040901:Proteomics
chemical_list: D007328:Insulin