RGD Reference Report - Tissue-specific PAI-1 gene expression and glycosylation pattern in insulin-resistant old rats. - Rat Genome Database

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Tissue-specific PAI-1 gene expression and glycosylation pattern in insulin-resistant old rats.

Authors: Serrano, R  Barrenetxe, J  Orbe, J  Rodriguez, JA  Gallardo, N  Martinez, C  Andres, A  Paramo, JA 
Citation: Serrano R, etal., Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1563-9. doi: 10.1152/ajpregu.00093.2009. Epub 2009 Sep 23.
RGD ID: 8547949
Pubmed: PMID:19776253   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpregu.00093.2009   (Journal Full-text)

Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with obesity, aging, insulin resistance, and type 2 diabetes, conditions that contribute to increased cardiovascular risk. PAI-1 is expressed in a variety of tissues, but the cellular origin of plasma PAI-1 is unknown. To link insulin resistance, aging, and cardiovascular disease, we examined the expression and glycosylation pattern of PAI-1 in liver and white adipose tissue (WAT) from adult (3 mo) and insulin-resistant old (24 mo) Wistar rats. Glycosylated PAI-1 protein was also purified by affinity chromatography from endothelial culture supernatans to analyze its inhibitory activity. We also analyzed the contribution of adipocytes and stromal vascular cells from WAT to PAI-1 levels with aging. Aging caused a significant increase of PAI-1 mRNA (P < 0.001) in WAT that was predominantly due to the adipocytes and not to stroma-vascular cells, while there was no modification in liver from aged rats. Moreover, PAI-1 expression increased during preadipocyte differentiation (P < 0.001). Furthermore, we found a tissue-dependent PAI-1 glycosylation pattern: adipose tissue only expresses the glycosylated PAI-1 form, whereas the liver mainly expresses the nonglycosylated form. Finally, we also found evidences suggesting that the glycosylated PAI-1 form shows higher inhibitory activity than the nonglycosylated. Our data suggest that WAT may be a major source of the elevated plasma levels of PAI-1 in insulin-resistant old rats. Additionally, the high degree of PAI-1 glycosylation and activity, together with the significant increase in visceral fat in old rats, may well contribute to an increased cardiovascular risk associated with insulin-resistant states.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Insulin Resistance  ISOSerpine1 (Rattus norvegicus)8547949; 8547949mRNA:increased expression:white adipose tissue (rat)RGD 
Insulin Resistance  IEP 8547949mRNA:increased expression:white adipose tissue (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpine1  (serpin family E member 1)

Genes (Mus musculus)
Serpine1  (serine (or cysteine) peptidase inhibitor, clade E, member 1)

Genes (Homo sapiens)
SERPINE1  (serpin family E member 1)


Additional Information