Glucose Controls the Expression of Polypyrimidine Tract-Binding Protein 1 via the Insulin Receptor Signaling Pathway in Pancreatic β Cells
Da Eun Jeong1,3, Sungeun Heo1,3, Ji Hye Han1, Eun-young Lee1, Rohit N. Kulkarni2, and Wook Kim1,*
1Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea, 2Department of Islet Cell and Regenerative Biology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, and Harvard Stem Cell Institute, Boston, MA 02215, USA, 3These authors contributed equally to this work.
*Correspondence: wookkim21@ajou.ac.kr
Received March 28, 2018; Revised August 6, 2018; Accepted August 9, 2018.; Published online August 31, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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ABSTRACT
In pancreatic β 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 β cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in β cells. PTBP1 is present in β 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 β cells established from wild-type (βIRWT) mice are higher than levels in β cells established from IR-null (βIRKO) mice, and ectopic re-expression of IR-WT in βIRKO cells restored PTBP1 levels. However, PTBP1 levels were not altered in βIRKO 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 βIRWT cells, but not in βIRKO 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 β cells.
Keywords: glucose, insulin, insulin receptor signaling, pancreatic β cell, PTBP1


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31 August 2018 Volume 41,
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