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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.10
- 수록면
- 909 - 916 (8page)
- DOI
- 10.14348/molcells.2018.0147
이용수
초록· 키워드
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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.
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등록된 정보가 없습니다.
참고문헌 (31)
참고문헌 신청
Assmann, A. / 2009 / Glucose effects on beta-cell growth and survival require activation of insulin receptors and insulin receptor substrate 2 / Mol. Cell Biol. 29:3219~3228
Brunstedt, J. / 1982 / Direct effect of glucose on the preproinsulin mRNA level in isolated pancreatic islets / Biochem. Biophys. Res. Commun. 106:1383~1389
Dor, Y. / 2004 / Adult pancreatic beta-cells are formed by self-duplication rather than stemcell differentiation / Nature 429:41~46
Folli, F. / 2011 / Altered insulin receptor signalling and ${\beta}$ -cell cycle dynamics in type 2 diabetes mellitus / PLoS One 6:e28050
Georgia, S. / 2004 / Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass / J. Clin. Invest. 114:963~968
Brunstedt, J. / 1982 / Direct effect of glucose on the preproinsulin mRNA level in isolated pancreatic islets / Biochem. Biophys. Res. Commun. 106:1383~1389
Dor, Y. / 2004 / Adult pancreatic beta-cells are formed by self-duplication rather than stemcell differentiation / Nature 429:41~46
Folli, F. / 2011 / Altered insulin receptor signalling and
Georgia, S. / 2004 / Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass / J. Clin. Invest. 114:963~968
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