title: Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes.
abstract: The complex interplay of many cell types and the temporal heterogeneity of pancreatic islet composition obscure the direct role of resident alpha and beta cells in the development of Type 1 diabetes. Therefore, in addition to studying islets isolated from non-obese diabetic mice, we analyzed homogeneous cell populations of murine alpha (αTC-1) and beta (NIT-1) cell lines to understand the role and differential survival of these two predominant islet cell populations. A total of 56 proteins in NIT-1 cells and 50 in αTC-1 cells were differentially expressed when exposed to proinflammatory cytokines. The major difference in the protein expression between cytokine-treated NIT-1 and αTC-1 cells was free radical scavenging enzymes. A similar observation was made in cytokine-treated whole islets, where a comprehensive analysis of subcellular fractions revealed that 438 unique proteins were differentially expressed under inflammatory conditions. Our data indicate that beta cells are relatively susceptible to ER and oxidative stress and reveal key pathways that are dysregulated in beta cells during cytokine exposure. Additionally, in the islets, inflammation also leads to enhanced antigen presentation, which completes a three-way insult on beta cells, rendering them targets of infiltrating T lymphocytes.
authors.affiliation: Department of Biochemistry and Molecular Biology, ‡The Bio21 Molecular Science and Biotechnology Institute, §Oral Health Cooperative Research Centre, Melbourne Dental School, and Bio21 Institute, ∥Departments of Paediatrics and Pharmacology, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Dhana G
authors.initials: DG
authors.lastname: Gorasia
authors.forename: Nadine L
authors.initials: NL
authors.lastname: Dudek
authors.forename: Paul D
authors.initials: PD
authors.lastname: Veith
authors.forename: Renu
authors.initials: R
authors.lastname: Shankar
authors.forename: Helena
authors.initials: H
authors.lastname: Safavi-Hemami
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Williamson
authors.forename: Eric C
authors.initials: EC
authors.lastname: Reynolds
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hubbard
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018384:Oxidative Stress
keywords: 2D-DIGE; Diabetes; ER stress; MALDI-TOF MS; inflammation; oxidative stress