Age-related autocrine diabetogenic effects of transgenic resistin in spontaneously hypertensive rats: gene expression profile analysis
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
HL-35018
NHLBI NIH HHS - United States
HL-56028
NHLBI NIH HHS - United States
HL-63709
NHLBI NIH HHS - United States
PubMed
21285283
PubMed Central
PMC3092332
DOI
10.1152/physiolgenomics.00112.2010
PII: physiolgenomics.00112.2010
Knihovny.cz E-zdroje
- MeSH
- glukózový toleranční test MeSH
- inzulinová rezistence genetika fyziologie MeSH
- krysa rodu Rattus MeSH
- polymerázová řetězová reakce MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- resistin genetika metabolismus MeSH
- stanovení celkové genové exprese metody MeSH
- stárnutí genetika metabolismus MeSH
- tuková tkáň metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- resistin MeSH
Increased circulating levels of resistin have been proposed as a possible link between obesity and insulin resistance; however, many of the potential metabolic effects of resistin remain to be investigated, including systemic versus local resistin action. We investigated potential autocrine effects of resistin on lipid and glucose metabolism in 2- and 16-mo-old transgenic spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin under control of the aP2 promoter. To search for possible molecular mechanisms, we compared gene expression profiles in adipose tissue in 6-wk-old transgenic SHR versus control rats, before development of insulin resistance, by digital transcriptional profiling using high-throughput sequencing. Both young and old transgenic rats showed moderate expression of the resistin transgene in adipose tissue but had serum resistin levels similar to control SHR and undetectable levels of transgenic resistin in the circulation. Young transgenic rats exhibited mild glucose intolerance. In contrast, older transgenic rats displayed marked glucose intolerance in association with near total resistance of adipose tissue to insulin-stimulated glucose incorporation into lipids (6 ± 2 vs. 77 ± 19 nmol glucose·g(-1)·2 h(-1), P < 0.00001). Ingenuity Pathway Analysis of differentially expressed genes revealed calcium signaling, Nuclear factor-erythroid 2-related factor-2 (NRF2)-mediated oxidative stress response, and actin cytoskeletal signaling canonical pathways as those most significantly affected. Analysis using DAVID software revealed oxidative phosphorylation, glutathione metabolism, pyruvate metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling as top Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These results suggest that with increasing age autocrine effects of resistin in fat tissue may predispose to diabetes in part by impairing insulin action in adipose tissue.
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