Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2003-7-14
pubmed:abstractText
In 3T3-L1 adipocytes, hyperosmotic stress was found to inhibit insulin signaling, leading to an insulin-resistant state. We show here that, despite normal activation of insulin receptor, hyperosmotic stress inhibits both tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphoinositide 3 (PI 3)-kinase activity in response to physiological insulin concentrations. Insulin-induced membrane ruffling, which is dependent on PI 3-kinase activation, was also markedly reduced. These inhibitory effects were associated with an increase in IRS-1 Ser307 phosphorylation. Furthermore, the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented the osmotic shock-induced phosphorylation of IRS-1 on Ser307. The inhibition of mTOR completely reversed the inhibitory effect of hyperosmotic stress on insulin-induced IRS-1 tyrosine phosphorylation and PI 3-kinase activation. In addition, prolonged osmotic stress enhanced the degradation of IRS proteins through a rapamycin-insensitive pathway and a proteasome-independent process. These data support evidence of new mechanisms involved in osmotic stress-induced cellular insulin resistance. Short-term osmotic stress induces the phosphorylation of IRS-1 on Ser307 by an mTOR-dependent pathway. This, in turn, leads to a decrease in early proximal signaling events induced by physiological insulin concentrations. On the other hand, prolonged osmotic stress alters IRS-1 function by inducing its degradation, which could contribute to the down-regulation of insulin action.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Serine, http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus, http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine, http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, mouse
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26550-7
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12730242-3T3 Cells, pubmed-meshheading:12730242-Adipocytes, pubmed-meshheading:12730242-Animals, pubmed-meshheading:12730242-Cell Membrane, pubmed-meshheading:12730242-Enzyme Activation, pubmed-meshheading:12730242-Insulin, pubmed-meshheading:12730242-Insulin Receptor Substrate Proteins, pubmed-meshheading:12730242-Insulin Resistance, pubmed-meshheading:12730242-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:12730242-Mice, pubmed-meshheading:12730242-Osmotic Pressure, pubmed-meshheading:12730242-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12730242-Phosphoproteins, pubmed-meshheading:12730242-Phosphorylation, pubmed-meshheading:12730242-Protein Kinase Inhibitors, pubmed-meshheading:12730242-Protein Kinases, pubmed-meshheading:12730242-Receptor, Insulin, pubmed-meshheading:12730242-Serine, pubmed-meshheading:12730242-Signal Transduction, pubmed-meshheading:12730242-Sirolimus, pubmed-meshheading:12730242-TOR Serine-Threonine Kinases, pubmed-meshheading:12730242-Tyrosine
pubmed:year
2003
pubmed:articleTitle
Hyperosmotic stress inhibits insulin receptor substrate-1 function by distinct mechanisms in 3T3-L1 adipocytes.
pubmed:affiliation
INSERM U 568 and l'Institut Fédératif de Recherches 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 02, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't