Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes
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Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes. / Gorasia, Dhana G; Dudek, Nadine L; Veith, Paul D; Shankar, Renu; Safavi-Hemami, Helena; Williamson, Nicholas A; Reynolds, Eric C; Hubbard, Michael J; Purcell, Anthony W.
I: Journal of Proteome Research, Bind 14, Nr. 2, 2015, s. 688-99.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes
AU - Gorasia, Dhana G
AU - Dudek, Nadine L
AU - Veith, Paul D
AU - Shankar, Renu
AU - Safavi-Hemami, Helena
AU - Williamson, Nicholas A
AU - Reynolds, Eric C
AU - Hubbard, Michael J
AU - Purcell, Anthony W
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Animals
KW - Blotting, Western
KW - Diabetes Mellitus, Experimental/metabolism
KW - Endoplasmic Reticulum/metabolism
KW - Islets of Langerhans/metabolism
KW - Mice
KW - Mice, Inbred NOD
KW - Oxidative Stress
U2 - 10.1021/pr500643h
DO - 10.1021/pr500643h
M3 - Journal article
C2 - 25412008
VL - 14
SP - 688
EP - 699
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 2
ER -
ID: 232824485