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.
Highlights
Type 1 diabetes (T1D) is a chronic, inflammatory disease widely considered to result from the autoimmune destruction of the insulin-producing pancreatic beta cells, leading to severe insulin deficiency and chronic hyperglycemia [1,2,3]
We have compared the proteomic profile of pancreas tissue from no disease (ND), AAb+, T1D, and type 2 diabetes (T2D) donors using a label-free proteomic approach (S1 Fig). 1,167 proteins were identified from the combined MS runs, consisting of 1,147 proteins from ND, 1,143 from AAb+, 1,149 from T1D and 1,132 proteins from T2D cases; of these, 1,085 proteins were shared among the four groups
Sixty tissue proteins with functional relevance to T1D were found to be significantly upregulated compared to ND, AAb+, and T2D cases
Summary
Type 1 diabetes (T1D) is a chronic, inflammatory disease widely considered to result from the autoimmune destruction of the insulin-producing pancreatic beta cells, leading to severe insulin deficiency and chronic hyperglycemia [1,2,3]. Human leukocyte antigen genotypes and islet autoantibodies are currently the most useful biomarkers for T1D risk prediction. Serological appearance of one or more autoantibodies against islet cell antigens (i.e., glutamic acid decarboxylase, insulin, protein tyrosine phosphatase, and zinc transporter Slc30A8 protein) is among the first detectable signs of emerging beta cell autoimmunity [4,5]. Autoantibodies to these molecules are both diagnostic and prognostic of disease development; routine use of autoantibody levels as a diagnostic tool is cumbersome, at best. Due to the limitations of current biomarkers, there is an unmet clinical need to identify novel T1D biomarkers to improve the sensitivity and specificity of T1D prediction and disease monitoring after treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
