Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Glucose Controls the Expression of Polypyrimidine Tract-Binding Protein 1 via the Insulin Receptor Signaling Pathway in Pancreatic β Cells

  • Jeong, Da Eun (Department of Molecular Science and Technology, Ajou University) ;
  • Heo, Sungeun (Department of Molecular Science and Technology, Ajou University) ;
  • Han, Ji Hye (Department of Molecular Science and Technology, Ajou University) ;
  • Lee, Eun-young (Department of Molecular Science and Technology, Ajou University) ;
  • Kulkarni, Rohit N. (Department of Islet Cell and Regenerative Biology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, and Harvard Stem Cell Institute) ;
  • Kim, Wook (Department of Molecular Science and Technology, Ajou University)
  • Received : 2018.03.28
  • Accepted : 2018.08.09
  • Published : 2018.10.31
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Abstract

In pancreatic ${\beta}$ cells, glucose stimulates the biosynthesis of insulin at transcriptional and post-transcriptional levels. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), also named hnRNP I, acts as a critical mediator of insulin biosynthesis through binding to the pyrimidine-rich region in the 3'-untranslated region (UTR) of insulin mRNA. However, the underlying mechanism that regulates its expression in ${\beta}$ cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in ${\beta}$ cells. PTBP1 is present in ${\beta}$ cells of both mouse and monkey, where its levels are increased by glucose and insulin, but not by insulin-like growth factor 1. PTBP1 levels in immortalized ${\beta}$ cells established from wild-type (${\beta}IRWT$) mice are higher than levels in ${\beta}$ cells established from IR-null (${\beta}IRKO$) mice, and ectopic re-expression of IR-WT in ${\beta}IRKO$ cells restored PTBP1 levels. However, PTBP1 levels were not altered in ${\beta}IRKO$ cells transfected with IR-3YA, in which the Tyr1158/1162/1163 residues are substituted with Ala. Consistently, treatment with glucose or insulin elevated PTBP1 levels in ${\beta}IRWT$ cells, but not in ${\beta}IRKO$ cells. In addition, silencing Akt significantly lowered PTBP1 levels. Thus, our results identify insulin as a pivotal mediator of glucose-induced PTBP1 expression in pancreatic ${\beta}$ cells.

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References

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