http://purl.uniprot.org/citations/18840784 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/18840784 | http://www.w3.org/2000/01/rdf-schema#comment | "ObjectiveThere is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3beta (GSK-3beta). Here, we investigate the role of GSK-3beta inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes.Research design and methodsRats with streptozotocin-induced diabetes were subjected to 30-min occlusion of common carotid arteries followed by 1 or 24 h of reperfusion. Insulin (2-12 IU/kg i.v.) or the selective GSK-3beta inhibitor TDZD-8 (0.2-3 mg/kg i.v.) was administered during reperfusion.ResultsInsulin or TDZD-8 dramatically reduced infarct volume and levels of S100B protein, a marker of cerebral injury. Both drugs induced phosphorylation of the Ser9 residue, thereby inactivating GSK-3beta in the rat hippocampus. Insulin, but not TDZD-8, lowered blood glucose. The hippocampi of the drug-treated animals displayed reduced oxidative stress at 1 h of reperfusion as shown by the decreased generation of reactive oxygen species and lipid peroxidation. I/R-induced activation of nuclear factor-kappaB was attenuated by both drug treatments. At 24 h of reperfusion, TDZD-8 and insulin significantly reduced plasma levels of tumor necrosis factor-alpha; neutrophil infiltration, measured as myeloperoxidase activity and intercellular-adhesion-molecule-1 expression; and cyclooxygenase-2 and inducible-NO-synthase expression.ConclusionsAcute administration of insulin or TDZD-8 reduced cerebral I/R injury in diabetic rats. We propose that the inhibitory effect on the activity of GSK-3beta contributes to the protective effect of insulin independently of any effects on blood glucose."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.org/dc/terms/identifier | "doi:10.2337/db08-0691"xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/author | "Aragno M."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/author | "Fantozzi R."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/author | "Thiemermann C."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/author | "Boccuzzi G."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/author | "Collino M."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/author | "Castiglia S."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/author | "Tomasinelli C."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/name | "Diabetes"xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/pages | "235-242"xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/title | "Insulin reduces cerebral ischemia/reperfusion injury in the hippocampus of diabetic rats: a role for glycogen synthase kinase-3beta."xsd:string |
http://purl.uniprot.org/citations/18840784 | http://purl.uniprot.org/core/volume | "58"xsd:string |
http://purl.uniprot.org/citations/18840784 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18840784 |
http://purl.uniprot.org/citations/18840784 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18840784 |
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http://purl.uniprot.org/uniprot/#_P04631-mappedCitation-18840784 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18840784 |
http://purl.uniprot.org/uniprot/#_P18266-mappedCitation-18840784 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18840784 |
http://purl.uniprot.org/uniprot/P04631 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18840784 |
http://purl.uniprot.org/uniprot/P18266 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18840784 |
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http://purl.uniprot.org/uniprot/A0A8I6A0X7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18840784 |