Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes

Dhana G Gorasia, Nadine Lee Dudek, Paul D Veith, Renu Shankar, Helena Safavi-Hemami, Nicholas A Williamson, Eric C Reynolds, Michael J Hubbard, Anthony W Purcell

Research output: Contribution to journalArticleResearchpeer-review

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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 (alphaTC-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 alphaTC-1 cells were differentially expressed when exposed to proinflammatory cytokines. The major difference in the protein expression between cytokine-treated NIT-1 and alphaTC-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.
Original languageEnglish
Pages (from-to)688 - 699
Number of pages12
JournalJournal of Proteome Research
Volume14
Issue number2
DOIs
Publication statusPublished - 2015

Cite this

Gorasia, Dhana G ; Dudek, Nadine Lee ; Veith, Paul D ; Shankar, Renu ; Safavi-Hemami, Helena ; Williamson, Nicholas A ; Reynolds, Eric C ; Hubbard, Michael J ; Purcell, Anthony W. / Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes. In: Journal of Proteome Research. 2015 ; Vol. 14, No. 2. pp. 688 - 699.
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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 (alphaTC-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 alphaTC-1 cells were differentially expressed when exposed to proinflammatory cytokines. The major difference in the protein expression between cytokine-treated NIT-1 and alphaTC-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.",
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Gorasia, DG, Dudek, NL, Veith, PD, Shankar, R, Safavi-Hemami, H, Williamson, NA, Reynolds, EC, Hubbard, MJ & Purcell, AW 2015, 'Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes', Journal of Proteome Research, vol. 14, no. 2, pp. 688 - 699. https://doi.org/10.1021/pr500643h

Pancreatic beta cells are highly susceptible to oxidative and ER stresses during the development of diabetes. / Gorasia, Dhana G; Dudek, Nadine Lee; Veith, Paul D; Shankar, Renu; Safavi-Hemami, Helena; Williamson, Nicholas A; Reynolds, Eric C; Hubbard, Michael J; Purcell, Anthony W.

In: Journal of Proteome Research, Vol. 14, No. 2, 2015, p. 688 - 699.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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AU - Gorasia, Dhana G

AU - Dudek, Nadine Lee

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 (alphaTC-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 alphaTC-1 cells were differentially expressed when exposed to proinflammatory cytokines. The major difference in the protein expression between cytokine-treated NIT-1 and alphaTC-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 (alphaTC-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 alphaTC-1 cells were differentially expressed when exposed to proinflammatory cytokines. The major difference in the protein expression between cytokine-treated NIT-1 and alphaTC-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.

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