JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis

Research output: Contribution to journalJournal articlepeer-review

Standard

JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis. / Prause, Michala; Christensen, Dan Ploug; Billestrup, Nils; Mandrup-Poulsen, Thomas.

In: PLOS ONE, Vol. 9, No. 1, e87067, 2014, p. 1-11.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Prause, M, Christensen, DP, Billestrup, N & Mandrup-Poulsen, T 2014, 'JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis', PLOS ONE, vol. 9, no. 1, e87067, pp. 1-11. https://doi.org/10.1371/journal.pone.0087067

APA

Prause, M., Christensen, D. P., Billestrup, N., & Mandrup-Poulsen, T. (2014). JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis. PLOS ONE, 9(1), 1-11. [e87067]. https://doi.org/10.1371/journal.pone.0087067

Vancouver

Prause M, Christensen DP, Billestrup N, Mandrup-Poulsen T. JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis. PLOS ONE. 2014;9(1):1-11. e87067. https://doi.org/10.1371/journal.pone.0087067

Author

Prause, Michala ; Christensen, Dan Ploug ; Billestrup, Nils ; Mandrup-Poulsen, Thomas. / JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis. In: PLOS ONE. 2014 ; Vol. 9, No. 1. pp. 1-11.

Bibtex

@article{b6615fca7bdf4b079338890dec8119d6,
title = "JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis",
abstract = "Pancreatic β-cell dysfunction is central to type 2 diabetes pathogenesis. Prolonged elevated levels of circulating free-fatty acids and hyperglycemia, also termed glucolipotoxicity, mediate β-cell dysfunction and apoptosis associated with increased c-Jun N-terminal Kinase (JNK) activity. Endoplasmic reticulum (ER) and oxidative stress are elicited by palmitate and high glucose concentrations further potentiating JNK activity. Our aim was to determine the role of the JNK subtypes JNK1, JNK2 and JNK3 in palmitate and high glucose-induced β-cell apoptosis. We established insulin-producing INS1 cell lines stably expressing JNK subtype specific shRNAs to understand the differential roles of the individual JNK isoforms. JNK activity was increased after 3 h of palmitate and high glucose exposure associated with increased expression of ER and mitochondrial stress markers. JNK1 shRNA expressing INS1 cells showed increased apoptosis and cleaved caspase 9 and 3 compared to non-sense shRNA expressing control INS1 cells when exposed to palmitate and high glucose associated with increased CHOP expression, ROS formation and Puma mRNA expression. JNK2 shRNA expressing INS1 cells did not affect palmitate and high glucose induced apoptosis or ER stress markers, but increased Puma mRNA expression compared to non-sense shRNA expressing INS1 cells. Finally, JNK3 shRNA expressing INS1 cells did not induce apoptosis compared to non-sense shRNA expressing INS1 cells when exposed to palmitate and high glucose but showed increased caspase 9 and 3 cleavage associated with increased DP5 and Puma mRNA expression. These data suggest that JNK1 protects against palmitate and high glucose-induced β-cell apoptosis associated with reduced ER and mitochondrial stress.",
author = "Michala Prause and Christensen, {Dan Ploug} and Nils Billestrup and Thomas Mandrup-Poulsen",
year = "2014",
doi = "10.1371/journal.pone.0087067",
language = "English",
volume = "9",
pages = "1--11",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

RIS

TY - JOUR

T1 - JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis

AU - Prause, Michala

AU - Christensen, Dan Ploug

AU - Billestrup, Nils

AU - Mandrup-Poulsen, Thomas

PY - 2014

Y1 - 2014

N2 - Pancreatic β-cell dysfunction is central to type 2 diabetes pathogenesis. Prolonged elevated levels of circulating free-fatty acids and hyperglycemia, also termed glucolipotoxicity, mediate β-cell dysfunction and apoptosis associated with increased c-Jun N-terminal Kinase (JNK) activity. Endoplasmic reticulum (ER) and oxidative stress are elicited by palmitate and high glucose concentrations further potentiating JNK activity. Our aim was to determine the role of the JNK subtypes JNK1, JNK2 and JNK3 in palmitate and high glucose-induced β-cell apoptosis. We established insulin-producing INS1 cell lines stably expressing JNK subtype specific shRNAs to understand the differential roles of the individual JNK isoforms. JNK activity was increased after 3 h of palmitate and high glucose exposure associated with increased expression of ER and mitochondrial stress markers. JNK1 shRNA expressing INS1 cells showed increased apoptosis and cleaved caspase 9 and 3 compared to non-sense shRNA expressing control INS1 cells when exposed to palmitate and high glucose associated with increased CHOP expression, ROS formation and Puma mRNA expression. JNK2 shRNA expressing INS1 cells did not affect palmitate and high glucose induced apoptosis or ER stress markers, but increased Puma mRNA expression compared to non-sense shRNA expressing INS1 cells. Finally, JNK3 shRNA expressing INS1 cells did not induce apoptosis compared to non-sense shRNA expressing INS1 cells when exposed to palmitate and high glucose but showed increased caspase 9 and 3 cleavage associated with increased DP5 and Puma mRNA expression. These data suggest that JNK1 protects against palmitate and high glucose-induced β-cell apoptosis associated with reduced ER and mitochondrial stress.

AB - Pancreatic β-cell dysfunction is central to type 2 diabetes pathogenesis. Prolonged elevated levels of circulating free-fatty acids and hyperglycemia, also termed glucolipotoxicity, mediate β-cell dysfunction and apoptosis associated with increased c-Jun N-terminal Kinase (JNK) activity. Endoplasmic reticulum (ER) and oxidative stress are elicited by palmitate and high glucose concentrations further potentiating JNK activity. Our aim was to determine the role of the JNK subtypes JNK1, JNK2 and JNK3 in palmitate and high glucose-induced β-cell apoptosis. We established insulin-producing INS1 cell lines stably expressing JNK subtype specific shRNAs to understand the differential roles of the individual JNK isoforms. JNK activity was increased after 3 h of palmitate and high glucose exposure associated with increased expression of ER and mitochondrial stress markers. JNK1 shRNA expressing INS1 cells showed increased apoptosis and cleaved caspase 9 and 3 compared to non-sense shRNA expressing control INS1 cells when exposed to palmitate and high glucose associated with increased CHOP expression, ROS formation and Puma mRNA expression. JNK2 shRNA expressing INS1 cells did not affect palmitate and high glucose induced apoptosis or ER stress markers, but increased Puma mRNA expression compared to non-sense shRNA expressing INS1 cells. Finally, JNK3 shRNA expressing INS1 cells did not induce apoptosis compared to non-sense shRNA expressing INS1 cells when exposed to palmitate and high glucose but showed increased caspase 9 and 3 cleavage associated with increased DP5 and Puma mRNA expression. These data suggest that JNK1 protects against palmitate and high glucose-induced β-cell apoptosis associated with reduced ER and mitochondrial stress.

U2 - 10.1371/journal.pone.0087067

DO - 10.1371/journal.pone.0087067

M3 - Journal article

C2 - 24475223

VL - 9

SP - 1

EP - 11

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e87067

ER -

ID: 113810150