ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells

Gabriela da Silva Xavier; Gao Sun; Qingwen Qian; Guy A. Rutter; Isabelle Leclerc

doi:10.1016/j.bbrc.2010.10.010

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ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells

Journal article

Open access

Peer reviewed

ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells

Gabriela da Silva Xavier, Gao Sun, Qingwen Qian, Guy A. Rutter and Isabelle Leclerc

Biochemical and biophysical research communications, Vol.402(2-2), pp.252-257

11/12/2010

DOI: 10.1016/j.bbrc.2010.10.010

PMCID: PMC2989445

PMID: 20934404

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Abstract

► ChREBP silencing enhances glucose-responsive gene expression in MIN6 β-cells. ► ChREBP modulation of Pdx-1 gene expression might be indirect. ► ChREBP over-expression decreases Pdx-1, MafA, Ins1, Ins2 and GcK mRNA levels in mouse pancreatic islets of Langerhans. Carbohydrate responsive element-binding protein (ChREBP) is a transcription factor whose expression and activity are increased in pancreatic β-cells maintained at elevated glucose concentrations. We show here that ChREBP inactivation in clonal pancreatic MIN6 β-cells results in an increase in Pdx-1 expression at low glucose and to a small, but significant, increase in Ins2 , GcK and MafA gene expression at high glucose concentrations. Conversely, adenovirus-mediated over-expression of ChREBP in mouse pancreatic islets results in decreases in Pdx-1, MafA, Ins1, Ins2 and GcK mRNA levels. These data suggest that strategies to reduce ChREBP activity might protect against β-cell dysfunction in type 2 diabetes.

ARNT, aryl hydrocarbon receptor nuclear translocator

ChIP, chromatin immunoprecipitation

ChoRE, carbohydrate-responsive element

ChREBP

ChREBP, carbohydrate responsive element-binding protein

FAS, fatty acid synthase

GcK, glucokinase

Gene expression

GFP, green fluorescent protein

Glucokinase

HIF, hypoxia inducible factor

Insulin

Islets of Langerhans

L-PK, L-type pyruvate kinase

MafA

MIN6

Pancreatic β-cells

Pdx-1

Pdx-1, pancreatic and duodenum homeobox-1

siRNA, small interfering RNA

SREBP-1c, sterol regulatory response-element-binding protein-1c

USF, upstream stimulatory factor

Details

Title: Subtitle: ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic β-cells
Creators: Gabriela da Silva Xavier - Imperial College London
Gao Sun - Imperial College London
Qingwen Qian - Imperial College London
Guy A. Rutter - Imperial College London
Isabelle Leclerc - Imperial College London
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.402(2-2), pp.252-257
DOI: 10.1016/j.bbrc.2010.10.010
PMID: 20934404
PMCID: PMC2989445
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: Academic Press
Grant note: DOI: 10.13039/501100000361, name: Diabetes UK, award: BDA:RD04/0002895; name: Wellcome Trust, award: WT082366MA, 081958/2/07/Z; name: The European Union; name: Medical Research Council, award: G0401641
Language: English
Date published: 11/12/2010
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984420845302771

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