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http://purl.uniprot.org/citations/19797171http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19797171http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Obesity is a risk factor for cardiovascular dysfunction, yet the underlying factors driving this impaired function remain poorly understood. Insulin resistance is a common pathology in obese patients and has been shown to impair vascular function. Whether insulin resistance or obesity, itself, is causal remains unclear.

Objective

The present study tested the hypothesis that insulin resistance is the underlying mediator for impaired NO-mediated dilation in obesity by genetic deletion of the insulin-desensitizing enzyme protein tyrosine phosphatase (PTP)1B in db/db mice.

Methods and results

The db/db mouse is morbidly obese, insulin-resistant, and has tissue-specific elevation in PTP1B expression compared to lean controls. In db/db mice, PTP1B deletion improved glucose clearance, dyslipidemia, and insulin receptor signaling in muscle and fat. Hepatic insulin signaling in db/db mice was not improved by deletion of PTP1B, indicating specific amelioration of peripheral insulin resistance. Additionally, obese mice demonstrate an impaired endothelium dependent and independent vasodilation to acetylcholine and sodium nitroprusside, respectively. This impairment, which correlated with increased superoxide in the db/db mice, was corrected by superoxide scavenging. Increased superoxide production was associated with increased expression of NAD(P)H oxidase 1 and its molecular regulators, Noxo1 and Noxa1.

Conclusions

Deletion of PTP1B improved both endothelium dependent and independent NO-mediated dilation and reduced superoxide generation in db/db mice. PTP1B deletion did not affect any vascular function in lean mice. Taken together, these data reveal a role for peripheral insulin resistance as the mediator of vascular dysfunction in obesity."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.109.206318"xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Muta K."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Tremblay M.L."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Black S.M."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Fulton D.J."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Stepp D.W."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Ali M.I."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Marrero M.B."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Ketsawatsomkron P."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Belin de Chantemele E.J."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Mintz J.D."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/author"Salet C."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/pages"1013-1022"xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/title"Deletion of protein tyrosine phosphatase 1b improves peripheral insulin resistance and vascular function in obese, leptin-resistant mice via reduced oxidant tone."xsd:string
http://purl.uniprot.org/citations/19797171http://purl.uniprot.org/core/volume"105"xsd:string
http://purl.uniprot.org/citations/19797171http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19797171
http://purl.uniprot.org/citations/19797171http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19797171
http://purl.uniprot.org/uniprot/#_D0FZQ3-mappedCitation-19797171http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19797171
http://purl.uniprot.org/uniprot/#_A2AV66-mappedCitation-19797171http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19797171
http://purl.uniprot.org/uniprot/#_P35821-mappedCitation-19797171http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19797171
http://purl.uniprot.org/uniprot/#_P48356-mappedCitation-19797171http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19797171
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