Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress
DC Field | Value | Language |
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dc.contributor.author | Jung, Tae Woo | - |
dc.contributor.author | Kim, Hyung-Chun | - |
dc.contributor.author | Abd El-Aty, A. M. | - |
dc.contributor.author | Jeong, Ji Hoon | - |
dc.date.available | 2019-03-08T08:38:16Z | - |
dc.date.issued | 2017-06 | - |
dc.identifier.issn | 0898-6568 | - |
dc.identifier.issn | 1873-3913 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/4355 | - |
dc.description.abstract | Several studies have shown that protectins, which are ca-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-H0-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis. | - |
dc.format.extent | 8 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.title | Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.cellsig.2017.03.013 | - |
dc.identifier.bibliographicCitation | CELLULAR SIGNALLING, v.34, pp 133 - 140 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000401388600014 | - |
dc.identifier.scopusid | 2-s2.0-85016492107 | - |
dc.citation.endPage | 140 | - |
dc.citation.startPage | 133 | - |
dc.citation.title | CELLULAR SIGNALLING | - |
dc.citation.volume | 34 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | Protectin DX | - |
dc.subject.keywordAuthor | Gluconeogenesis | - |
dc.subject.keywordAuthor | Endoplasmic reticulum stress | - |
dc.subject.keywordAuthor | AMP-activated protein kinase | - |
dc.subject.keywordAuthor | Heme oxygenase 1 | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | HEME OXYGENASE-1 GENE | - |
dc.subject.keywordPlus | GLUCOSE-HOMEOSTASIS | - |
dc.subject.keywordPlus | INSULIN ACTION | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | INJURY | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | DEPHOSPHORYLATION | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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