DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Yong Deuk | ko |
dc.contributor.author | Kim, Yong-Hoon | ko |
dc.contributor.author | Tadi, Surendar | ko |
dc.contributor.author | Yu, Ji Hoon | ko |
dc.contributor.author | Yim, Yong-Hyeon | ko |
dc.contributor.author | Jeoung, Nam Ho | ko |
dc.contributor.author | Shong, Minho | ko |
dc.contributor.author | Hennighausen, Lothar | ko |
dc.contributor.author | Harris, Robert A. | ko |
dc.contributor.author | Lee, In-Kyu | ko |
dc.contributor.author | Lee, Chul-Ho | ko |
dc.contributor.author | Choi, Hueng-Sik | ko |
dc.date.accessioned | 2023-04-12T07:00:24Z | - |
dc.date.available | 2023-04-12T07:00:24Z | - |
dc.date.created | 2023-04-12 | - |
dc.date.created | 2023-04-12 | - |
dc.date.issued | 2012-10 | - |
dc.identifier.citation | DIABETES, v.61, no.10, pp.2484 - 2494 | - |
dc.identifier.issn | 0012-1797 | - |
dc.identifier.uri | http://hdl.handle.net/10203/306161 | - |
dc.description.abstract | Growth hormone (GH) is a counter-regulatory hormone that plays an important role in preventing hypoglycemia during fasting. Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin. The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice. Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation. Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction. The increase in PDK4 expression and PDC phosphorylation by GH was reduced in STAT5-null mice. Metformin decreased GH-mediated induction of PDK4 expression and metabolites in wildtype but not in SHP-null mice. In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression. SHP directly inhibited STAT5 association on the PDK4 gene promoter. Metformin inhibits GH-induced PDK4 expression and metabolites via an AMPK-SHP-dependent pathway. The metformin-AMPK-SHP network may provide a novel therapeutic approach for the treatment of hepatic metabolic disorders induced by the GH-mediated pathway. Diabetes 61:2484-2494, 2012 | - |
dc.language | English | - |
dc.publisher | AMER DIABETES ASSOC | - |
dc.title | Metformin Inhibits Growth Hormone-Mediated Hepatic PDK4 Gene Expression Through Induction of Orphan Nuclear Receptor Small Heterodimer Partner | - |
dc.type | Article | - |
dc.identifier.wosid | 000309304600013 | - |
dc.identifier.scopusid | 2-s2.0-84866601834 | - |
dc.type.rims | ART | - |
dc.citation.volume | 61 | - |
dc.citation.issue | 10 | - |
dc.citation.beginningpage | 2484 | - |
dc.citation.endingpage | 2494 | - |
dc.citation.publicationname | DIABETES | - |
dc.identifier.doi | 10.2337/db11-1665 | - |
dc.contributor.localauthor | Shong, Minho | - |
dc.contributor.nonIdAuthor | Kim, Yong Deuk | - |
dc.contributor.nonIdAuthor | Kim, Yong-Hoon | - |
dc.contributor.nonIdAuthor | Tadi, Surendar | - |
dc.contributor.nonIdAuthor | Yu, Ji Hoon | - |
dc.contributor.nonIdAuthor | Yim, Yong-Hyeon | - |
dc.contributor.nonIdAuthor | Jeoung, Nam Ho | - |
dc.contributor.nonIdAuthor | Hennighausen, Lothar | - |
dc.contributor.nonIdAuthor | Harris, Robert A. | - |
dc.contributor.nonIdAuthor | Lee, In-Kyu | - |
dc.contributor.nonIdAuthor | Lee, Chul-Ho | - |
dc.contributor.nonIdAuthor | Choi, Hueng-Sik | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | PYRUVATE-DEHYDROGENASE COMPLEX | - |
dc.subject.keywordPlus | SIGNAL TRANSDUCER | - |
dc.subject.keywordPlus | GLUCOSE-PRODUCTION | - |
dc.subject.keywordPlus | TRANSCRIPTION | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | STAT5B | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.