Linked Life Data

12684063

Source:http://linkedlifedata.com/resource/pubmed/id/12684063

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-4-9
pubmed:abstractText
Insulin gene transcription is critical for the maintenance of pancreatic beta-cell differentiation and insulin production. In this study, we found that the basic helix-loop-helix transcription factor Mad, which usually acts as a repressor to c-Myc, enhances insulin gene transcription. In isolated rat islets adenoviral overexpression of Mad augmented insulin mRNA expression and insulin protein content, as well as glucokinase and GLUT2 mRNA expression. Also, Mad overexpression upregulated insulin promoter activity in beta-cell-derived cell lines, MIN6 and betaTC1, as well as in non-insulin producing liver cell line, HepG2. Mad overexpression in rat islets enhanced PDX-1 expression and its DNA binding activity. We found that Mad mediated increased PDX-1 expression by an E-box dependent transcriptional regulation of the PDX-1 gene. That the effects of Mad on insulin expression were mediated through PDX-1 was further substantiated by studies showing inhibition of insulin promoter activation by Mad in the presence of mutated PDX-1 binding site. Although Mad functions as a negative regulatory factor for multiple target genes, these studies establish the fact that Mad can also function as a positive regulatory factor for insulin gene transcription. Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
303
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1199-208
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Induction of Mad expression leads to augmentation of insulin gene transcription.
pubmed:affiliation
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't