carboxypeptidase-b and Diabetes-Mellitus--Type-1

Type 1 diabetes (T1D) is characterized by autoimmune mediated self-destruction of the pancreatic islet beta cells and the resultant insulin deficiency. However, little is known about the underlying molecular pathogenesis at the pancreatic tissue level given the limited availability of clinical specimens.. Quantitative proteomic studies is performed on age-matched T1D and healthy cadaveric pancreatic tissues (n = 18 each) using TMT 10plex-based isobaric labeling and BoxCar-based label-free LC-MS/MS approaches. ELISA is used to validate the differentially expressed proteins (DEPs).. Overall, the two quantitative proteomics approaches identified 8824 proteins, of which 261 are DEPs. KEGG pathway and functional network analyses of the DEPs reveal dysregulations to pancreatic exocrine function, complement coagulation cascades, and extracellular matrix receptor interaction pathways in T1D. A selected list of the DEPs associated with pathways, subnetworks, and plasma proteome of T1D are validated using ELISA.. Integrating labeling and label-free approaches improve the confidence in quantitative profiling of pancreatic tissue proteome, which furthers the understanding of the dysregulated pathways and functional subnetworks associated with T1D pathogenesis and may aid to develop diagnostic and therapeutic strategies for T1D.

Topics: Adolescent; Adult; Biomarkers; Carboxypeptidase B; Case-Control Studies; Collagen Type VI; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Pancreas; Proteome; Proteomics; Young Adult

A reliable, noninvasive indicator of pancreatic allograft rejection is urgently needed. In this study, serum (S), plasma (P), and urine (U) levels of pancreas-specific protein (P-PASP, U-PASP), neopterin (S-NEOP, U-NEOP), amylase (U-AMYL), and amyloid A (SAA) were measured daily in ten type I diabetic patients following simultaneous pancreas and kidney transplantation (SPK). Rejection episodes occurred in three isolated pancreas, nine isolated kidney, and five simultaneous pancreas and kidney transplants. In the case of the eight pancreas rejections, SAA was the rejection marker with the highest diagnostic accuracy (94%). Using P-PASP and U-PASP, an accuracy of 81% and 79%, respectively, was achieved. During viral infections, U-NEOP levels increased to a maximum level of 1904 mumol/mol creatinine, whereas during bacterial infections, SAA levels increased to a maximum value of 43 mg/dl. SAA, measured for the first time in SPK, appears to be a valuable rejection parameter. In combination with U-NEOP and U-AMYL, a differential diagnosis between rejection, bacterial infection, and viral infection was possible. Neither U-PASP nor P-PASP monitoring led to a significant improvement in the results.

Topics: Acute Disease; Adult; Apolipoproteins; Bacterial Infections; Biopterins; Carboxypeptidase B; Carboxypeptidases; Diabetes Mellitus, Type 1; Female; Graft Rejection; Humans; Kidney Transplantation; Male; Neopterin; Pancreas Transplantation; Pilot Projects; Proteins; Serum Amyloid A Protein; Virus Diseases