RGD Reference Report - JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis. - Rat Genome Database

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JNK1 protects against glucolipotoxicity-mediated beta-cell apoptosis.

Authors: Prause, M  Christensen, DP  Billestrup, N  Mandrup-Poulsen, T 
Citation: Prause M, etal., PLoS One. 2014 Jan 24;9(1):e87067. doi: 10.1371/journal.pone.0087067. eCollection 2014.
RGD ID: 10047243
Pubmed: PMID:24475223   (View Abstract at PubMed)
PMCID: PMC3901710   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0087067   (Journal Full-text)

Pancreatic beta-cell dysfunction is central to type 2 diabetes pathogenesis. Prolonged elevated levels of circulating free-fatty acids and hyperglycemia, also termed glucolipotoxicity, mediate beta-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 beta-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 beta-cell apoptosis associated with reduced ER and mitochondrial stress.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type B pancreatic cell apoptotic process involved_inIMP 10047243PMID:24475223CACAO 

Objects Annotated

Genes (Rattus norvegicus)
Mapk8  (mitogen-activated protein kinase 8)


Additional Information