Linked Life Data

10579310

Source:http://linkedlifedata.com/resource/pubmed/id/10579310

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-12-20
pubmed:abstractText
Organ weight was compared in adult mice with deletion of one (IRS-1-/+) or both (IRS-1-/-) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1+/+ littermates. IRS-1-/+ mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1-/- mice showed major reductions in weight of heart, liver, and spleen that were directly proportional to a decrease in body weight. In IRS-1-/- mice, kidney and particularly small intestine and brain exhibited proportionately smaller weight reductions, and gastrocnemius muscle showed a proportionately greater weight reduction than the decrease in body weight. Growth deficits in IRS-1-/- mice could reflect impaired actions of multiple hormones or cytokines that activate IRS-1. To assess the requirement for IRS-1 in insulin-like growth factor I (IGF-I)-dependent postnatal growth, IRS-1-/+ mice were cross-bred with mice that widely overexpress a human IGF-I transgene (IGF+) to generate IGF+ and wild-type mice on an IRS-1+/+, IRS-1-/+, and IRS-1-/- background. IGF-I overexpression increased body weight and weight of brain, small intestine, kidney, spleen, heart, and gastrocnemius muscle in IRS-1+/+ mice. IGF-I overexpression could not completely reverse the body growth retardation in IRS-1-/- mice. Absolute or partial IRS-1 deficiency impaired IGF-I-induced body overgrowth more in females than in males. In males and females, IGF-I stimulated similar overgrowth of brain regardless of IRS-1 status, and intestine and spleen showed dose dependence on IRS-1 for IGF-I-induced growth. IGF-I-induced growth of gastrocnemius muscle had an absolute requirement for IRS-1. IGF-I-induced growth of kidney and heart was impaired by IRS-1 deficiency only in females. In vivo, therefore, most organs do not require IRS-1 for IGF-I-induced growth and can use alternate signaling molecules to mediate IGF-I action. Other organs, such as gastrocnemius muscle, require IRS-1 for IGF-I-induced growth in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5478-87
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10579310-Animals, pubmed-meshheading:10579310-Brain, pubmed-meshheading:10579310-Crosses, Genetic, pubmed-meshheading:10579310-Female, pubmed-meshheading:10579310-Gene Deletion, pubmed-meshheading:10579310-Growth, pubmed-meshheading:10579310-Heart, pubmed-meshheading:10579310-Humans, pubmed-meshheading:10579310-Insulin Receptor Substrate Proteins, pubmed-meshheading:10579310-Insulin-Like Growth Factor I, pubmed-meshheading:10579310-Intestine, Small, pubmed-meshheading:10579310-Kidney, pubmed-meshheading:10579310-Liver, pubmed-meshheading:10579310-Male, pubmed-meshheading:10579310-Mice, pubmed-meshheading:10579310-Mice, Transgenic, pubmed-meshheading:10579310-Organ Size, pubmed-meshheading:10579310-Phosphoproteins, pubmed-meshheading:10579310-RNA, Messenger, pubmed-meshheading:10579310-Spleen, pubmed-meshheading:10579310-Weight Loss
pubmed:year
1999
pubmed:articleTitle
Postnatal growth responses to insulin-like growth factor I in insulin receptor substrate-1-deficient mice.
pubmed:affiliation
Department of Physiology, University of North Carolina, Chapel 27599-7545, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't