Linked Life Data

10650980

Source:http://linkedlifedata.com/resource/pubmed/id/10650980

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-2-28
pubmed:abstractText
Nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) is the target of antidiabetogenic thiazolidinediones (TZD). However, recent studies failed to show that TZD has an effect in vitro on insulin-regulated glucose uptake in skeletal muscles, the major site of glucose disposal. The potential effects of TZD on cells adjacent to skeletal muscles are not well characterized but may be involved in TZD's actions. Hence, we studied these cells from mice treated with the carrier and with the TZD ciglitazone (9 nmol/g body weight). The cells were typified by lipid enrichment (floating adipocytes and macrophages), by the ectopic expression of cellular fibronectin (fibroblasts), fibronectin and PPARgamma (preadipocytes), PPARgamma and CD11b/Mac-1 (active macrophages) as revealed by flow cytometry and immunoblotting. The glucose transporter 4 proteins (GLUT4) and the uptake of glucose and long-chain fatty acids (LCFA) were determined flow cytometrically using fluorescent derivatives of glucose (NBDG) and LCFA (C16-Bodipy). The expression of tumor necrosis factor alpha (TNFalpha) in CD11b/Mac-1-positive and CD11b/Mac-1-negative cells separated by magnetic immunobeads was analyzed. The results showed that TZD treatment upregulated GLUT4 expression, and increased insulin-regulated NBDG uptake and C16-Bodipy binding and influx, at the same time as increasing the quantity of PPARgamma-expressing fibroblasts; this indicates the development of the preadipocyte phenotype. In contrast, TZD lowered the number of adipocytes (0.6-fold compared to the carrier-treated control) perhaps through an action of TNFalpha from CD11b- and PPARgamma-expressing macrophages. The data suggest that the regulatory effects of TZD on energy homeostasis involve two major targets: the PPARgamma-positive fibroblasts whose adipogenic program is promoted, and CD11b-PPARgamma-expressing macrophages which become cytotoxic and fibrogenic because of the effects of TNFalpha on neighboring adipocytes and fibroblasts, respectively.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0031-6768
pubmed:author
pubmed:issnType
Print
pubmed:volume
439
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
288-96
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10650980-Adipocytes, pubmed-meshheading:10650980-Animals, pubmed-meshheading:10650980-Blotting, Western, pubmed-meshheading:10650980-Cell Separation, pubmed-meshheading:10650980-DNA, Complementary, pubmed-meshheading:10650980-Down-Regulation, pubmed-meshheading:10650980-Fatty Acids, pubmed-meshheading:10650980-Fibroblasts, pubmed-meshheading:10650980-Flow Cytometry, pubmed-meshheading:10650980-Glucose, pubmed-meshheading:10650980-Homeostasis, pubmed-meshheading:10650980-Hypoglycemic Agents, pubmed-meshheading:10650980-Immunohistochemistry, pubmed-meshheading:10650980-Macrophages, pubmed-meshheading:10650980-Male, pubmed-meshheading:10650980-Mice, pubmed-meshheading:10650980-Mice, Obese, pubmed-meshheading:10650980-Muscle, Skeletal, pubmed-meshheading:10650980-RNA, Messenger, pubmed-meshheading:10650980-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:10650980-Thiazoles, pubmed-meshheading:10650980-Thiazolidinediones, pubmed-meshheading:10650980-Transcription Factors, pubmed-meshheading:10650980-Tumor Necrosis Factor-alpha
pubmed:year
2000
pubmed:articleTitle
Thiazolidinedione-induced activation of the transcription factor peroxisome proliferator-activated receptor gamma in cells adjacent to the murine skeletal muscle: implications for fibroblast functions.
pubmed:affiliation
Research Institute of Animal Biology, Dummerstorf-Rostock, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't