Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2011-9-22
pubmed:abstractText
Deiodinases are selenoproteins that activate or inactivate thyroid hormone. During vertebrate development, these pathways control thyroid hormone action in a cell-specific fashion explaining how systemic thyroid hormone can affect local control of tissue embryogenesis. Here we investigated the role of the thyroid hormone-inactivating deiodinase (D3) in pancreatic islet function and glucose homeostasis. D3 expression was determined by real-time PCR, immunofluorescence, and enzyme activity. Embryonic and adult wild-type mice and Mice with targeted disruption of Dio3 gene (D3KO) as well as human fetal pancreas and adult islets were studied. Insulin secretion was evaluated in adult mouse isolated islets. We found Dio3 gene expression and protein highly expressed in embryonic and adult pancreatic islets, predominantly in ?-cells in both humans and mice. However, mRNA levels were barely detectable for both the thyroid hormone-activating deiodinases types 1 and 2. D3KO animals were found to be glucose intolerant due to in vitro and in vivo impaired glucose-stimulated insulin secretion, without changes in peripheral sensitivity to insulin. D3KO neonatal (postnatal day 0) and adult pancreas exhibited reduced total islet area due to reduced ?-cell mass, insulin content, and impaired expression of key ?-cells genes. D3 expression in perinatal pancreatic ?-cells prevents untimely exposure to thyroid hormone, the absence of which leads to impaired ?-cell function and subsequently insulin secretion and glucose homeostasis. An analogous role is likely in humans, given the similar D3 expression pattern.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3717-27
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The thyroid hormone-inactivating type III deiodinase is expressed in mouse and human beta-cells and its targeted inactivation impairs insulin secretion.
pubmed:affiliation
Division of Endocrinology, Diabetes, and Metabolism, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural