PKB/Akt phosphorylation of ERR gamma contributes to insulin-mediated inhibition of hepatic gluconeogenesis
DC Field | Value | Language |
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dc.contributor.author | Kim, Don-Kyu | - |
dc.contributor.author | Kim, Yong-Hoon | - |
dc.contributor.author | Hynx, Debby | - |
dc.contributor.author | Wang, Yanning | - |
dc.contributor.author | Yang, Keum-Jin | - |
dc.contributor.author | Ryu, Dongryeol | - |
dc.contributor.author | Kim, Kyung Seok | - |
dc.contributor.author | Yoo, Eun-Kyung | - |
dc.contributor.author | Kim, Jeong-Sun | - |
dc.contributor.author | Koo, Seung-Hoi | - |
dc.contributor.author | Lee, In-Kyu | - |
dc.contributor.author | Chae, Ho-Zoon | - |
dc.contributor.author | Park, Jongsun | - |
dc.contributor.author | Lee, Chul-Ho | - |
dc.contributor.author | Biddinger, Sudha B. | - |
dc.contributor.author | Hemmings, Brian A. | - |
dc.contributor.author | Choi, Hueng-Sik | - |
dc.date.accessioned | 2021-09-05T02:36:08Z | - |
dc.date.available | 2021-09-05T02:36:08Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-12 | - |
dc.identifier.issn | 0012-186X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/96670 | - |
dc.description.abstract | Insulin resistance, a major contributor to the pathogenesis of type 2 diabetes, leads to increased hepatic glucose production (HGP) owing to an impaired ability of insulin to suppress hepatic gluconeogenesis. Nuclear receptor oestrogen-related receptor gamma (ERR gamma) is a major transcriptional regulator of hepatic gluconeogenesis. In this study, we investigated insulin-dependent post-translational modifications (PTMs) altering the transcriptional activity of ERR gamma for the regulation of hepatic gluconeogenesis. We examined insulin-dependent phosphorylation and subcellular localisation of ERR gamma in cultured cells and in the liver of C57/BL6, leptin receptor-deficient (db/db), liver-specific insulin receptor knockout (LIRKO) and protein kinase B (PKB) beta-deficient (Pkb beta (-/-)) mice. To demonstrate the role of ERR gamma in the inhibitory action of insulin on hepatic gluconeogenesis, we carried out an insulin tolerance test in C57/BL6 mice expressing wild-type or phosphorylation-deficient mutant ERR gamma. We demonstrated that insulin suppressed the transcriptional activity of ERR gamma by promoting PKB/Akt-mediated phosphorylation of ERR gamma at S179 and by eliciting translocation of ERR gamma from the nucleus to the cytoplasm through interaction with 14-3-3, impairing its ability to promote hepatic gluconeogenesis. In addition, db/db, LIRKO and Pkb beta (-/-) mice displayed enhanced ERR gamma transcriptional activity due to a block in PKB beta-mediated ERR gamma phosphorylation during refeeding. Finally, the phosphorylation-deficient mutant ERR gamma S179A was resistant to the inhibitory action of insulin on HGP. These results suggest that ERR gamma is a major contributor to insulin action in maintaining hepatic glucose homeostasis. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | SPRINGER | - |
dc.subject | GLUCOSE-PRODUCTION | - |
dc.subject | RECEPTOR-ALPHA | - |
dc.subject | TRANSCRIPTIONAL ACTIVITY | - |
dc.subject | GENE-TRANSCRIPTION | - |
dc.subject | INVERSE AGONIST | - |
dc.subject | MICE LACKING | - |
dc.subject | LIVER | - |
dc.subject | COACTIVATOR | - |
dc.subject | HOMEOSTASIS | - |
dc.subject | METABOLISM | - |
dc.title | PKB/Akt phosphorylation of ERR gamma contributes to insulin-mediated inhibition of hepatic gluconeogenesis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Koo, Seung-Hoi | - |
dc.identifier.doi | 10.1007/s00125-014-3366-x | - |
dc.identifier.scopusid | 2-s2.0-84926656626 | - |
dc.identifier.wosid | 000344630700021 | - |
dc.identifier.bibliographicCitation | DIABETOLOGIA, v.57, no.12, pp.2576 - 2585 | - |
dc.relation.isPartOf | DIABETOLOGIA | - |
dc.citation.title | DIABETOLOGIA | - |
dc.citation.volume | 57 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 2576 | - |
dc.citation.endPage | 2585 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.subject.keywordPlus | GLUCOSE-PRODUCTION | - |
dc.subject.keywordPlus | RECEPTOR-ALPHA | - |
dc.subject.keywordPlus | TRANSCRIPTIONAL ACTIVITY | - |
dc.subject.keywordPlus | GENE-TRANSCRIPTION | - |
dc.subject.keywordPlus | INVERSE AGONIST | - |
dc.subject.keywordPlus | MICE LACKING | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | COACTIVATOR | - |
dc.subject.keywordPlus | HOMEOSTASIS | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordAuthor | Akt/PKB | - |
dc.subject.keywordAuthor | Hepatic gluconeogenesis | - |
dc.subject.keywordAuthor | Insulin receptor signalling | - |
dc.subject.keywordAuthor | Nuclear hormone receptor | - |
dc.subject.keywordAuthor | Phosphorylation | - |
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