CCCTC-binding factor mediates effects of glucose on beta cell survival.

Autor: Tsui S; Department of Medicine, David Geffen School of Medicine University of California Los Angeles, Torrance, CA, 90502, USA., Dai W, Lu L
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2014 Feb; Vol. 47 (1), pp. 28-37. Date of Electronic Publication: 2013 Dec 20.
DOI: 10.1111/cpr.12085
Abstrakt: Objectives: Pancreatic islet β-cell survival is paramount for regulation of insulin activity and for maintaining glucose homeostasis. Recently, Pax6 has been shown to be essential for many vital functions in β-cells, although many molecular mechanisms of its homeostasis in β-cells remain unclear. The present study investigates novel effects of glucose- and insulin-induced CCCTC-binding factor (CTCF) activity on Pax6 gene expression as well as for subsequent effects of insulin-activated signalling pathways, on β-cell proliferation.
Materials and Methods: Pancreatic β-TC-1-6 cells were cultured in DMEM and stimulated with high concentrations of glucose (5-125 mm); cell viability was assessed by MTT assay. Effects of CTCF on Pax6 were evaluated in the high glucose-induced environment and CTCF/Erk-suppressed cells, by promoter reporter and western blotting analyses.
Results: Increases in glucose and insulin concentrations upregulated CTCF and consequently downregulated Pax6 in β-cell survival and proliferation. Knocking-down CTCF directly affected Pax6 transcription through CTCF binding and blocked the response to glucose. Altered Erk activity mediated effects of CTCF on controlling Pax6 expression, which partially regulated β-cell proliferation.
Conclusions: CTCF functioned as a molecular mediator between insulin-induced upstream Erk signalling and Pax6 expression in these pancreatic β-cells. This pathway may contribute to regulation of β-cell survival and proliferation.
(© 2013 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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