Linked Life Data

19336477

Source:http://linkedlifedata.com/resource/pubmed/id/19336477

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-5-25
pubmed:abstractText
Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome is a recently described autosomal recessive disorder associated with predominantly antibody negative, insulin-dependent diabetes mellitus. In order to identify the genetic basis of PHID and study its relationship with glucose metabolism, we performed homozygosity mapping in five unrelated families followed by candidate gene sequencing. Five loss-of-function mutations were identified in the SLC29A3 gene which encodes a member of a highly conserved protein family that transports nucleosides, nucleobases and nucleoside analogue drugs, hENT3. We show that PHID is allelic with a related syndrome without diabetes mellitus, H syndrome. The interaction of SLC29A3 with insulin signaling pathways was then studied using an established model in Drosophila melanogaster. Ubiquitous knockdown of the Drosophila ortholog of hENT3, dENT1 is lethal under stringent conditions; whereas milder knockdown induced scutellar bristle phenotypes similar to those previously reported in the knockdown of the Drosophila ortholog of the Islet gene. A cellular growth assay showed a reduction of cell size/number which could be rescued or enhanced by manipulation of the Drosophila insulin receptor and its downstream signaling effectors, dPI3K and dAkt. In summary, inactivating mutations in SLC29A3 cause a syndromic form of insulin-dependent diabetes in humans and in Drosophila profoundly affect cell size/number through interactions with the insulin signaling pathway. These data suggest that further investigation of the role of SLC29A3 in glucose metabolism is a priority for diabetes research.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2257-65
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19336477-Amino Acid Sequence, pubmed-meshheading:19336477-Animals, pubmed-meshheading:19336477-Base Sequence, pubmed-meshheading:19336477-Diabetes Mellitus, Type 1, pubmed-meshheading:19336477-Disease Models, Animal, pubmed-meshheading:19336477-Drosophila Proteins, pubmed-meshheading:19336477-Drosophila melanogaster, pubmed-meshheading:19336477-Female, pubmed-meshheading:19336477-Humans, pubmed-meshheading:19336477-Hypertrichosis, pubmed-meshheading:19336477-Insulin, pubmed-meshheading:19336477-Male, pubmed-meshheading:19336477-Molecular Sequence Data, pubmed-meshheading:19336477-Mutation, pubmed-meshheading:19336477-Nucleoside Transport Proteins, pubmed-meshheading:19336477-Pedigree, pubmed-meshheading:19336477-Receptor, Insulin, pubmed-meshheading:19336477-Sequence Alignment, pubmed-meshheading:19336477-Signal Transduction, pubmed-meshheading:19336477-Skin Pigmentation
pubmed:year
2009
pubmed:articleTitle
SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway.
pubmed:affiliation
Department of Haematology and Genetics, South Eastern Area Laboratory Services, Sydney, NSW 2031, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't