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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.4
- 수록면
- 356 - 361 (6page)
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Mitochondrial dysfunction is associated with insulin resistance and diabetes. We previously showed that retinoid X receptor α (RXRα) played an important role in transcriptional regulation of oxidative phosphorylation (OXPHOS) genes in cells with mitochondrial dysfunction caused by mitochondrial DNA mutation. In this study, we investigated whether mitochondrial dysfunction induced by incubation with OXPHOS inhibitors affects insulin receptor substrate 1 (IRS1) mRNA and protein levels and whether RXRα activation or overexpression can restore IRS1 expression.
Both IRS1 and RXRα protein levels were significantly reduced when C2C12 myotubes were treated with the OXPHOS complex inhibitors, rotenone and antimycin A.
The addition of RXRα agonists, 9-cis retinoic acid (9cRA) and LG1506, increased IRS1 transcription and protein levels and restored mitochondrial function, which ultimately improved insulin signaling. RXRα overexpression also increased IRS1 transcription and mitochondrial function.
Because RXRα overexpression, knock-down, or activation by LG1506 regulated IRS1 transcription mostly independently of mitochondrial function, it is likely that RXRα directly regulates IRS1 transcription. Consistent with the hypothesis, we showed that RXRα bound to the IRS1 promoter as a heterodimer with peroxisome proliferatoractivated receptor δ (PPARδ). These results suggest that RXRα overexpression or activation alleviates insulin resistance by increasing IRS1 expression.
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참고문헌 (27)
참고문헌 신청
Anderson, E. J. / 2009 / Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans / J. Clin. Invest 119:573~581
Cesario, R. M. / 2001 / The rexinoid LG100754 is a novel RXR : PPARgamma agonist and decreases glucose levels in vivo / Mol. Endocrinol 15:1360~1369
Chae, S. / 2013 / A systems approach for decoding mitochondrial retrograde signaling pathways / Sci. Signal 6:4
Egawa, K. / 2000 / Persistent activation of phosphatidylinositol 3-kinase causes insulin resistance due to accelerated insulin-induced insulin receptor substrate-1degradation in 3T3-L1 adipocytes / Endocrinology 141:1930~1935
Evans, R. M. / 2014 / Nuclear receptors, RXR, and the big bang / Cell 157:255~266
Cesario, R. M. / 2001 / The rexinoid LG100754 is a novel RXR : PPARgamma agonist and decreases glucose levels in vivo / Mol. Endocrinol 15:1360~1369
Chae, S. / 2013 / A systems approach for decoding mitochondrial retrograde signaling pathways / Sci. Signal 6:4
Egawa, K. / 2000 / Persistent activation of phosphatidylinositol 3-kinase causes insulin resistance due to accelerated insulin-induced insulin receptor substrate-1degradation in 3T3-L1 adipocytes / Endocrinology 141:1930~1935
Evans, R. M. / 2014 / Nuclear receptors, RXR, and the big bang / Cell 157:255~266
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