Linked Life Data

15182363

Source:http://linkedlifedata.com/resource/pubmed/id/15182363

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-6-8
pubmed:abstractText
Caveolae are plasma membrane invaginations with several functions, one of which appears to be to organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin receptor was localized to caveolae by electron microscopy/immunogold detection and by isolating caveolae from plasma membranes. Part of insulin receptor substrate 1 (IRS1), the immediate downstream signal mediator, was colocalized with the insulin receptor in the plasma membrane and caveolae, as demonstrated by immunofluorescence microscopy, immunogold electron microscopy, and immunogold electron microscopy of transfected recombinant HA-IRS1. In contrast, rat epididymal adipocytes lacked IRS1 at the plasma membrane. Depletion of cholesterol from the cells using beta-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation. Insulin-stimulated phosphorylation of the insulin receptor and IRS1 was not affected, indicating that caveolae integrity is required downstream of IRS1. In conclusion we show that insulin receptor and IRS1 are both caveolar proteins and that caveolae are required for both metabolic and mitogenic control in human adipocytes. Our results establish caveolae as foci of insulin action and stress the importance of examining human cells in addition to animal cells and cell lines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2471-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15182363-Adipose Tissue, pubmed-meshheading:15182363-Adult, pubmed-meshheading:15182363-Aged, pubmed-meshheading:15182363-Animals, pubmed-meshheading:15182363-Carrier Proteins, pubmed-meshheading:15182363-Caveolae, pubmed-meshheading:15182363-Cell Membrane, pubmed-meshheading:15182363-Cells, Cultured, pubmed-meshheading:15182363-Cholesterol, pubmed-meshheading:15182363-Female, pubmed-meshheading:15182363-Humans, pubmed-meshheading:15182363-Insulin, pubmed-meshheading:15182363-Insulin Receptor Substrate Proteins, pubmed-meshheading:15182363-Male, pubmed-meshheading:15182363-Middle Aged, pubmed-meshheading:15182363-Phosphoproteins, pubmed-meshheading:15182363-Phosphorylation, pubmed-meshheading:15182363-Rats, pubmed-meshheading:15182363-Receptor, Insulin, pubmed-meshheading:15182363-Signal Transduction
pubmed:year
2004
pubmed:articleTitle
Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes. Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control.
pubmed:affiliation
Department of Cell Biology and Diabetes Research Centre, University of Linköping, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't