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Keun Gyu Park  (Park KG) 1 Article
The Effect of Tribbles-Related Protein 3 on ER Stress-Suppressed Insulin Gene Expression in INS-1 Cells
Young Yun Jang, Nam Keong Kim, Mi Kyung Kim, Ho Young Lee, Sang Jin Kim, Hye Soon Kim, Hye-Young Seo, In Kyu Lee, Keun Gyu Park
Korean Diabetes J. 2010;34(5):312-319.   Published online October 31, 2010
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AbstractAbstract PDFPubReader   

The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression.


The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter.


The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression.


This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.


Citations to this article as recorded by  
  • Endoplasmic reticulum stress causes insulin resistance by inhibiting delivery of newly synthesized insulin receptors to the cell surface
    Max Brown, Samantha Dainty, Natalie Strudwick, Adina D. Mihai, Jamie N. Watson, Robina Dendooven, Adrienne W. Paton, James C. Paton, Martin Schröder, James Arthur Olzmann
    Molecular Biology of the Cell.2020; 31(23): 2597.     CrossRef
  • PTB and TIAR binding to insulin mRNA 3′- and 5′UTRs; implications for insulin biosynthesis and messenger stability
    Rikard G. Fred, Syrina Mehrabi, Christopher M. Adams, Nils Welsh
    Heliyon.2016; 2(9): e00159.     CrossRef
  • Asna1/TRC40 Controls β-Cell Function and Endoplasmic Reticulum Homeostasis by Ensuring Retrograde Transport
    Stefan Norlin, Vishal S. Parekh, Peter Naredi, Helena Edlund
    Diabetes.2016; 65(1): 110.     CrossRef
  • Role of the Unfolded Protein Response inβCell Compensation and Failure during Diabetes
    Nabil Rabhi, Elisabet Salas, Philippe Froguel, Jean-Sébastien Annicotte
    Journal of Diabetes Research.2014; 2014: 1.     CrossRef
  • Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review
    Mi-Kyung Kim, Hye-Soon Kim, In-Kyu Lee, Keun-Gyu Park
    Experimental Diabetes Research.2012; 2012: 1.     CrossRef

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