Insulin-inducible SMILE inhibits hepatic gluconeogenesis

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dc.contributor.authorJ M Lee-
dc.contributor.authorW Y Seo-
dc.contributor.authorH S Han-
dc.contributor.authorKyoung Jin Oh-
dc.contributor.authorY S Lee-
dc.contributor.authorD K Kim-
dc.contributor.authorS Choi-
dc.contributor.authorB H Choi-
dc.contributor.authorR A Harris-
dc.contributor.authorChul Ho Lee-
dc.contributor.authorS H Koo-
dc.contributor.authorH S Choi-
dc.date.accessioned2017-04-19T10:18:53Z-
dc.date.available2017-04-19T10:18:53Z-
dc.date.issued2016-
dc.identifier.issn00121797-
dc.identifier.uri10.2337/db15-0249ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/13190-
dc.description.abstractThe role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes.-
dc.publisherAmer Diabetes Assoc-
dc.titleInsulin-inducible SMILE inhibits hepatic gluconeogenesis-
dc.title.alternativeInsulin-inducible SMILE inhibits hepatic gluconeogenesis-
dc.typeArticle-
dc.citation.titleDiabetes-
dc.citation.number1-
dc.citation.endPage73-
dc.citation.startPage62-
dc.citation.volume65-
dc.contributor.affiliatedAuthorKyoung Jin Oh-
dc.contributor.affiliatedAuthorChul Ho Lee-
dc.contributor.alternativeName이지민-
dc.contributor.alternativeName서우영-
dc.contributor.alternativeName한혜숙-
dc.contributor.alternativeName오경진-
dc.contributor.alternativeName이용수-
dc.contributor.alternativeName김돈규-
dc.contributor.alternativeName최세리-
dc.contributor.alternativeName최병훈-
dc.contributor.alternativeNameHarris-
dc.contributor.alternativeName이철호-
dc.contributor.alternativeName구승회-
dc.contributor.alternativeName최흥식-
dc.identifier.bibliographicCitationDiabetes, vol. 65, no. 1, pp. 62-73-
dc.identifier.doi10.2337/db15-0249-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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