Linked Life Data

17923767

Source:http://linkedlifedata.com/resource/pubmed/id/17923767

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-10-9
pubmed:abstractText
Mutations in the genes encoding transcriptional regulators HNF1beta (TCF2), HNF1alpha (TCF1), and HNF4alpha cause autosomal dominant diabetes (also known as maturity-onset diabetes of the young). Herein, we review what we have learnt during recent years concerning the functions of these regulators in the developing and adult pancreas. Mouse studies have revealed that HNF1beta is a critical regulator of a transcriptional network that controls the specification, growth, and differentiation of the embryonic pancreas. HNF1beta mutations in humans accordingly often cause pancreas hypoplasia. By contrast, HNF1alpha and HNF4alpha have been shown to regulate the function of differentiated beta-cells. HNF1alpha and HNF4alpha mutations in patients thus cause decreased glucose-induced insulin secretion that leads to a progressive form of diabetes. HNF4alpha mutations paradoxically also cause in utero and neonatal hyperinsulinism, which later evolves to decreased glucose-induced secretion. Recent studies show that Hnf4alpha deficiency in mice causes not only abnormal insulin secretion, but also an impairment of the expansion of beta-cell mass that normally occurs during pregnancy. In line with this finding, we present data that Hnf1alpha-/- beta-cells expressing SV40 large T antigen show a severe impairment of proliferation and failure to form tumours. Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1421-7082
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-45
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth.
pubmed:affiliation
Genomic Programming of Beta Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Endocrinology, Hospital Clínic de Barcelona, Barcelona, Spain.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't