2017
DOI: 10.2337/db16-1352
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Apoptosis Repressor With Caspase Recruitment Domain Ameliorates Amyloid-Induced β-Cell Apoptosis and JNK Pathway Activation

Abstract: Islet amyloid is present in more than 90% of individuals with type 2 diabetes, where it contributes to β-cell apoptosis and insufficient insulin secretion. Apoptosis repressor with caspase recruitment domain (ARC) binds and inactivates components of the intrinsic and extrinsic apoptosis pathways and was recently found to be expressed in islet β-cells. Using a human islet amyloid polypeptide transgenic mouse model of islet amyloidosis, we show ARC knockdown increases amyloid-induced β-cell apoptosis and loss, w… Show more

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Cited by 22 publications
(16 citation statements)
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“…More recently, ARC was proven to inhibit the TNF-αpathway itself to block multiple downstream outcomes, including apoptosis, necrosis and NF-κB activation. 20 Exogenous ARC was also shown to bind JNK and inhibit its activation in hepatocytes and islet β-cells 21,22 . In this study, the RNAseq analysis revealed TNF-αsignal pathway was inhibited and Fgf-2 gene was up-regulated in ARC overexpressed BMSCs.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…More recently, ARC was proven to inhibit the TNF-αpathway itself to block multiple downstream outcomes, including apoptosis, necrosis and NF-κB activation. 20 Exogenous ARC was also shown to bind JNK and inhibit its activation in hepatocytes and islet β-cells 21,22 . In this study, the RNAseq analysis revealed TNF-αsignal pathway was inhibited and Fgf-2 gene was up-regulated in ARC overexpressed BMSCs.…”
Section: Discussionmentioning
confidence: 99%
“…Apoptosis repressor with caspase recruitment domain (ARC) also terms NOL3, is a highly potent and multifunctional inhibitor of apoptosis 8 . It is physiologically expressed in terminally differentiated cells, including cardiomyocytes, neurons and skeletal muscle cells 9 .…”
Section: Introductionmentioning
confidence: 99%
“…It was reported that β-cell mass decreased by approximately 40 and 65% in lean and obese individuals with T2DM, respectively, compared to the cell mass of age-and BMI-matched nondiabetic individuals. In approximately two-thirds of obese individuals who did not develop T2DM, pancreatic islet mass increased to compensate for increased insulin demand (22,23). Changes in β-cell mass might occur several years before hyperglycemia appears, as suggested by the United Kingdom Prospective Diabetes Study (UKPDS) (24).…”
Section: Discussionmentioning
confidence: 99%
“…ARC binds with and prevents the activation of JUN N-terminal kinase (JNK), inhibiting cell death dependent on the JNK signaling pathway (30,77,78). ARC blocks acetaminophen- induced hepatic damage by antagonizing the JNK signaling pathway and preventing ROS production (77).…”
Section: Cytoprotection and Anti-apoptosis Mechanisms Of Arcmentioning
confidence: 99%
“…ARC blocks acetaminophen- induced hepatic damage by antagonizing the JNK signaling pathway and preventing ROS production (77). ARC decreases amyloid-induced JNK phosphorylation, and ARC upregulation decreases β-cell apoptosis induced by activation of the JNK signaling pathway (78). Furthermore, ARC blocks Fas- and TNF-regulated cell death by JNK-dependent or independent pathways (30) (Fig.…”
Section: Cytoprotection and Anti-apoptosis Mechanisms Of Arcmentioning
confidence: 99%