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Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states
- Title
- Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states
- Authors
- Kang, Hye Suk; Cho, Ho-Chan; Lee, Jae-Ho; Oh, Goo Taeg; Koo, Seung-Hoi; Park, Byung-Hyun; Lee, In-Kyu; Choi, Hueng-Sik; Song, Dae-Kyu; Im, Seung-Soon
- Ewha Authors
- 오구택
- SCOPUS Author ID
- 오구택
- Issue Date
- 2016
- Journal Title
- SCIENTIFIC REPORTS
- ISSN
- 2045-2322
- Citation
- SCIENTIFIC REPORTS vol. 6
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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.
- DOI
- 10.1038/srep23665
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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