pr500643h_si_008.xlsx (1.86 MB)
Pancreatic Beta Cells Are Highly Susceptible to Oxidative and ER Stresses during the Development of Diabetes
dataset
posted on 2015-02-06, 00:00 authored by Dhana
G. Gorasia, Nadine L. Dudek, Paul D. Veith, Renu Shankar, Helena Safavi-Hemami, Nicholas A. Williamson, Eric C. Reynolds, Michael J. Hubbard, Anthony W. PurcellThe
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.