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Cited 15 times in

Chronic HMGCR/HMG-CoA Reductase Inhibitor Treatment Contributes to Dysglycemia by Upregulating Hepatic Gluconeogenesis through Autophagy Induction

DC FieldValueLanguage
dc.contributor.author강은석-
dc.contributor.author김철훈-
dc.contributor.author윤미진-
dc.contributor.author이명식-
dc.contributor.author이향규-
dc.contributor.author차봉수-
dc.contributor.author허규연-
dc.date.accessioned2016-02-04T12:04:03Z-
dc.date.available2016-02-04T12:04:03Z-
dc.date.issued2015-
dc.identifier.issn1554-8627-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/141817-
dc.description.abstractStatins (HMGCR/HMG-CoA reductase [3-hydroxy-3-methylglutaryl-CoA reductase] inhibitors) are widely used to lower blood cholesterol levels but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanism underlying diabetogenic effects remains to be elucidated. Here we show that statins significantly increase the expression of key gluconeogenic enzymes (such as G6PC [glucose-6-phosphatase] and PCK1 (phosphoenolpyruvate carboxykinase 1 [soluble]) in vitro and in vivo and promote hepatic glucose output. Statin treatment activates autophagic flux in HepG2 cells. Acute suppression of autophagy with lysosome inhibitors in statin treated HepG2 cells reduced gluconeogenic enzymes expression and glucose output. Importantly, the ability of statins to increase gluconeogenesis was impaired when ATG7 was deficient and BECN1 was absent, suggesting that autophagy plays a critical role in the diabetogenic effects of statins. Moreover autophagic vacuoles and gluconeogenic genes expression in the liver of diet-induced obese mice were increased by statins, ultimately leading to elevated hepatic glucose production, hyperglycemia, and insulin resistance. Together, these data demonstrate that chronic statin therapy results in insulin resistance through the activation of hepatic gluconeogenesis, which is tightly coupled to hepatic autophagy. These data further contribute to a better understanding of the diabetogenic effects of stains in the context of insulin resistance.-
dc.description.statementOfResponsibilityopen-
dc.format.extent2089~2101-
dc.relation.isPartOfAUTOPHAGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleChronic HMGCR/HMG-CoA Reductase Inhibitor Treatment Contributes to Dysglycemia by Upregulating Hepatic Gluconeogenesis through Autophagy Induction-
dc.typeArticle-
dc.contributor.collegeCollege of Nursing (간호대학)-
dc.contributor.departmentDept. of Nursing Environment Systems (임상간호과학과)-
dc.contributor.googleauthorHye Jin Wang-
dc.contributor.googleauthor, Jae Yeo Park-
dc.contributor.googleauthorEun Seok Kang-
dc.contributor.googleauthorHyangkyu Lee-
dc.contributor.googleauthorYoung-Bum Kim-
dc.contributor.googleauthorBong Soo Cha-
dc.contributor.googleauthorMijin Yun-
dc.contributor.googleauthorMyung-Shik Lee-
dc.contributor.googleauthorKyu Yeon Hur-
dc.contributor.googleauthorChul Hoon Kim-
dc.contributor.googleauthorEun Yeong Choe-
dc.contributor.googleauthorObin Kwon-
dc.identifier.doi10.1080/15548627.2015.1091139-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00068-
dc.contributor.localIdA01057-
dc.contributor.localIdA02550-
dc.contributor.localIdA02752-
dc.contributor.localIdA03282-
dc.contributor.localIdA03996-
dc.contributor.localIdA04343-
dc.relation.journalcodeJ00269-
dc.identifier.eissn1554-8635-
dc.identifier.pmid26389569-
dc.identifier.urlhttp://www.tandfonline.com/doi/full/10.1080/15548627.2015.1091139#.VlZkSHIw-Uk-
dc.subject.keywordHMG-CoA reductase inhibitor-
dc.subject.keywordautophagy-
dc.subject.keyworddiabetes-
dc.subject.keywordgluconeogenesis-
dc.subject.keywordstatin-
dc.contributor.alternativeNameKang, Eun Seok-
dc.contributor.alternativeNameKim, Chul Hoon-
dc.contributor.alternativeNameYun, Mi Jin-
dc.contributor.alternativeNameLee, Myung Shik-
dc.contributor.alternativeNameLee, Hyang Kyu-
dc.contributor.alternativeNameCha, Bong Soo-
dc.contributor.alternativeNameHur, Kyu Yeon-
dc.contributor.affiliatedAuthorKang, Eun Seok-
dc.contributor.affiliatedAuthorKim, Chul Hoon-
dc.contributor.affiliatedAuthorYun, Mi Jin-
dc.contributor.affiliatedAuthorLee, Myung Shik-
dc.contributor.affiliatedAuthorLee, Hyang Kyu-
dc.contributor.affiliatedAuthorCha, Bong Soo-
dc.contributor.affiliatedAuthorHur, Kyu Yeon-
dc.rights.accessRightsnot free-
dc.citation.volume11-
dc.citation.number11-
dc.citation.startPage2089-
dc.citation.endPage2101-
dc.identifier.bibliographicCitationAUTOPHAGY, Vol.11(11) : 2089-2101, 2015-
Appears in Collections:
3. College of Nursing (간호대학) > Dept. of Nursing (간호학과) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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