Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP = SHP의 AMPK-의존적 경로를 통한 metformin의 당신생억제효과

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dc.contributor.authorY D Kim-
dc.contributor.authorK G Park-
dc.contributor.authorY S Lee-
dc.contributor.authorY Y Park-
dc.contributor.authorD K Kim-
dc.contributor.authorB Nedumaran-
dc.contributor.authorW G Jang-
dc.contributor.authorW J Cho-
dc.contributor.authorJ Ha-
dc.contributor.authorI K Lee-
dc.contributor.authorChul Ho Lee-
dc.contributor.authorH S Choi-
dc.date.accessioned2017-04-19T09:11:37Z-
dc.date.available2017-04-19T09:11:37Z-
dc.date.issued2008-
dc.identifier.issn0012-1797-
dc.identifier.uri10.2337/db07-0381ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/8570-
dc.description.abstractOBJECTIVE: Metformin is an antidiabetic drug commonly used to treat type 2 diabetes. The aim of the study was to determine whether metformin regulates hepatic gluconeogenesis through the orphan nuclear receptor small heterodimer partner (SHP; NR0B2). RESEARCH DESIGN AND METHODS: We assessed the regulation of hepatic SHP gene expression by Northern blot analysis with metformin and adenovirus containing a constitutive active form of AMP-activated protein kinase (AMPK) (Ad-AMPK) and evaluated SHP, PEPCK, and G6Pase promoter activities via transient transfection assays in hepatocytes. Knockdown of SHP using siRNA SHP was conducted to characterize the metformin-induced inhibition of hepatic gluconeogenic gene expression in hepatocytes, and metformin-and adenovirus SHP (Ad-SHP)-mediated hepatic glucose production was measured in B6-Lep(ob/ob) mice. RESULTS: Hepatic SHP gene expression was induced by metformin, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and Ad-AMPK. Metformin-induced SHP gene expression was abolished by adenovirus containing the dominant negative form of AMPK (Ad-DN-AMPK), as well as by compound C. Metformin inhibited hepatocyte nuclear factor-4alpha-or FoxA2-mediated promoter activity of PEPCK and G6Pase, and the inhibition was blocked with siRNA SHP. Additionally, SHP knockdown by adenovirus containing siRNA SHP inhibited metformin-mediated repression of cAMP/dexamethasone-induced hepatic gluconeogenic gene expression. Furthermore, oral administration of metformin increased SHP mRNA levels in B6-Lep(ob/ob) mice. Overexpression of SHP by Ad-SHP decreased blood glucose levels and hepatic gluconeogenic gene expression in B6-Lep(ob/ob) mice. CONCLUSIONS: We have concluded that metformin inhibits hepatic gluconeogenesis through AMPK-dependent regulation of SHP.-
dc.publisherAmer Diabetes Assoc-
dc.titleMetformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP = SHP의 AMPK-의존적 경로를 통한 metformin의 당신생억제효과-
dc.title.alternativeMetformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP-
dc.typeArticle-
dc.citation.titleDiabetes-
dc.citation.number2-
dc.citation.endPage314-
dc.citation.startPage306-
dc.citation.volume57-
dc.contributor.affiliatedAuthorChul Ho Lee-
dc.contributor.alternativeName김용득-
dc.contributor.alternativeName박근규-
dc.contributor.alternativeName이용수-
dc.contributor.alternativeName박윤용-
dc.contributor.alternativeName김돈규-
dc.contributor.alternativeNameNedumaran-
dc.contributor.alternativeName장원구-
dc.contributor.alternativeName조원제-
dc.contributor.alternativeName하주훈-
dc.contributor.alternativeName이인규-
dc.contributor.alternativeName이철호-
dc.contributor.alternativeName최흥식-
dc.identifier.bibliographicCitationDiabetes, vol. 57, no. 2, pp. 306-314-
dc.identifier.doi10.2337/db07-0381-
dc.description.journalClassY-
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Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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