Open AccessCCCTC ‐binding factor mediates effects of glucose on beta cell survival
Author(s) -
Tsui S.,
Dai W.,
Lu L.
Publication year - 2014
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12085
Subject(s) - ctcf , mapk/erk pathway , pax6 , cell growth , microbiology and biotechnology , transcription factor , downregulation and upregulation , biology , glucose homeostasis , insulin , reporter gene , chemistry , endocrinology , signal transduction , gene expression , insulin resistance , genetics , gene , enhancer
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 m m ); 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.