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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 373 - 383 (11page)
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Our previous study revealed a novel role of Fas-associated death domain-containing protein (FADD) in islet development and insulin secretion. Insulin-degrading enzyme (IDE) is a zinc metalloprotease that selectively degrades biologically important substrates associated with type 2 diabetes (T2DM). The current study was designed to investigate the effect of FADD phosphorylation on IDE. We found that the mRNA and protein levels of IDE were significantly downregulated in FADD-D mouse livers compared with control mice. Quantitative real-time polymerase chain reaction analysis showed that FADD regulates the expression of IDE at the transcriptional level without affecting the stability of the mRNA in HepG2 cells. Following treatment with cycloheximide, the IDE protein degradation rate was found to be increased in both FADD-D primary hepatocytes and FADD-knockdown HepG2 cells. Additionally, IDE expression levels were reduced in insulin-stimulated primary hepatocytes from FADD-D mice compared to those from control mice. Moreover, FADD phosphorylation promotes nuclear translocation of FoxO1, thus inhibiting the transcriptional activity of the IDE promoter. Together, these findings imply a novel role of FADD in the reduction of protein stability and expression levels of IDE.
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참고문헌 (43)
참고문헌 신청
Abdul-Hay, S. O. / 2011 / Deletion of insulin-degrading enzyme elicits antipodal, agedependent effects on glucose and insulin tolerance / PLoS One 6:e20818
Bojsen-Moller, K. N. / 2018 / Hepatic insulin clearance in regulation of systemic insulin concentrations-role of carbohydrate and energy availability / Diabetes 67:2129~2136
Bonnefond, A. / 2010 / The emerging genetics of type 2 diabetes / Trends Mol. Med 16:407~416
Bonnet, M. C. / 2011 / The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation / Immunity 35:572~582
Cao, Y. / 2016 / SIRT1 and insulin resistance / J. Diabetes Complications 30:178~183
Bojsen-Moller, K. N. / 2018 / Hepatic insulin clearance in regulation of systemic insulin concentrations-role of carbohydrate and energy availability / Diabetes 67:2129~2136
Bonnefond, A. / 2010 / The emerging genetics of type 2 diabetes / Trends Mol. Med 16:407~416
Bonnet, M. C. / 2011 / The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation / Immunity 35:572~582
Cao, Y. / 2016 / SIRT1 and insulin resistance / J. Diabetes Complications 30:178~183
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