Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states
DC Field | Value | Language |
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dc.contributor.author | Kang, Hye Suk | - |
dc.contributor.author | Cho, Ho-Chan | - |
dc.contributor.author | Lee, Jae-Ho | - |
dc.contributor.author | Oh, Goo Taeg | - |
dc.contributor.author | Koo, Seung-Hoi | - |
dc.contributor.author | Park, Byung-Hyun | - |
dc.contributor.author | Lee, In-Kyu | - |
dc.contributor.author | Choi, Hueng-Sik | - |
dc.contributor.author | Song, Dae-Kyu | - |
dc.contributor.author | Im, Seung-Soon | - |
dc.date.accessioned | 2021-09-04T01:26:08Z | - |
dc.date.available | 2021-09-04T01:26:08Z | - |
dc.date.created | 2021-06-17 | - |
dc.date.issued | 2016-03-24 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/89191 | - |
dc.description.abstract | The anti-diabetic drug, metformin, exerts its action through AMP-activated protein kinase (AMPK), and Sirtuin (Sirt1) signaling. Insulin-like growth factor (IGF)-binding protein 2 (IGFBP-2) prevents IGF-1 binding to its receptors, thereby contributing to modulate insulin sensitivity. In this study, we demonstrate that metformin upregulates Igfbp-2 expression through the AMPK-Sirt1-PPAR alpha cascade pathway. In the liver of high fat diet, ob/ob, and db/db mice, Igfbp-2 expression was significantly decreased compared to the expression levels in the wild-type mice (p < 0.05). Upregulation of Igfbp-2 expression by metformin administration was disrupted by gene silencing of Ampk and Sirt1, and this phenomenon was not observed in Ppar alpha-null mice. Notably, activation of IGF-1 receptor (IGF-1R)dependent signaling by IGF-1 was inhibited by metformin. Finally, when compared to untreated type 2 diabetes patients, the metformin-treated diabetic patients showed increased IGFBP-2 levels with diminished serum IGF-1 levels. Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPA alpha-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | ACTIVATED PROTEIN-KINASE | - |
dc.subject | IGF-I | - |
dc.subject | PPAR-ALPHA | - |
dc.subject | BINDING PROTEIN-1 | - |
dc.subject | LIPID-METABOLISM | - |
dc.subject | INSULIN | - |
dc.subject | GROWTH | - |
dc.subject | SIRT1 | - |
dc.subject | OBESE | - |
dc.subject | LIVER | - |
dc.title | Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Koo, Seung-Hoi | - |
dc.identifier.doi | 10.1038/srep23665 | - |
dc.identifier.scopusid | 2-s2.0-84961669709 | - |
dc.identifier.wosid | 000372700100001 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.6 | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 6 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | IGF-I | - |
dc.subject.keywordPlus | PPAR-ALPHA | - |
dc.subject.keywordPlus | BINDING PROTEIN-1 | - |
dc.subject.keywordPlus | LIPID-METABOLISM | - |
dc.subject.keywordPlus | INSULIN | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | SIRT1 | - |
dc.subject.keywordPlus | OBESE | - |
dc.subject.keywordPlus | LIVER | - |
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