Type 1 diabetes cadaveric human pancreata exhibit a unique exocrine tissue proteomic profile

Abstract

Type 1 diabetes (T1D) is an autoimmune disorder resulting from a self-destruction of pancreatic islet beta cells. The complete proteome of the human pancreas, where both the dysfunctional beta cells and their proximal environment co-exist, remains unknown. Here, we used TMT10-based isobaric labeling and multidimensional LC-MS/MS to quantitatively profile the differences between pancreatic head region tissues from T1D (N = 5) and healthy subjects (N = 5). Among the 5357 (1% false discovery rate) confidently identified proteins, 145 showed statistically significant dysregulation between T1D and healthy subjects. The differentially expressed pancreatic proteome supports the growing notion of a potential role for exocrine pancreas involvement in T1D. This study also demonstrates the utility for this approach to analyze dysregulated proteins as a means to investigate islet biology, pancreatic pathology and T1D pathogenesis.

Keywords: Biomedicine; Isobaric labeling; Pancreas proteome; TMT10; Type 1 diabetes; nPOD.