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http://purl.uniprot.org/citations/20627936http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20627936http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Insulin resistance is associated with the pathogenesis of metabolic disorders as type 2 diabetes and obesity. Given the emerging role of signal transduction in these syndromes, we set out to explore the possible role that G protein-coupled receptor kinase 2 (GRK2), first identified as a G protein-coupled receptor regulator, could have as a modulator of insulin responses.

Research design and methods

We analyzed the influence of GRK2 levels in insulin signaling in myoblasts and adipocytes with experimentally increased or silenced levels of GRK2, as well as in GRK2 hemizygous animals expressing 50% lower levels of this kinase in three different models of insulin resistance: tumor necrosis factor-α (TNF-α) infusion, aging, and high-fat diet (HFD). Glucose transport, whole-body glucose and insulin tolerance, the activation status of insulin pathway components, and the circulating levels of important mediators were measured. The development of obesity and adipocyte size with age and HFD was analyzed.

Results

Altering GRK2 levels markedly modifies insulin-mediated signaling in cultured adipocytes and myocytes. GRK2 levels are increased by ∼2-fold in muscle and adipose tissue in the animal models tested, as well as in lymphocytes from metabolic syndrome patients. In contrast, hemizygous GRK2 mice show enhanced insulin sensitivity and do not develop insulin resistance by TNF-α, aging, or HFD. Furthermore, reduced GRK2 levels induce a lean phenotype and decrease age-related adiposity.

Conclusions

Overall, our data identify GRK2 as an important negative regulator of insulin effects, key to the etiopathogenesis of insulin resistance and obesity, which uncovers this protein as a potential therapeutic target in the treatment of these disorders."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.org/dc/terms/identifier"doi:10.2337/db10-0771"xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Lorenzo M."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Diez J."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Fernandez-Veledo S."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Mayor F. Jr."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Murga C."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Zalba G."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Jurado-Pueyo M."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Nieto-Vazquez I."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Vila-Bedmar R."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/author"Garcia-Guerra L."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/name"Diabetes"xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/pages"2407-2417"xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/title"G protein-coupled receptor kinase 2 plays a relevant role in insulin resistance and obesity."xsd:string
http://purl.uniprot.org/citations/20627936http://purl.uniprot.org/core/volume"59"xsd:string
http://purl.uniprot.org/citations/20627936http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20627936
http://purl.uniprot.org/citations/20627936http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20627936
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http://purl.uniprot.org/uniprot/#_A0A494B9J9-mappedCitation-20627936http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20627936
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