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http://purl.uniprot.org/citations/18792873http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18792873http://www.w3.org/2000/01/rdf-schema#comment"Advanced glycation end products (AGEs) could be implicated in insulin resistance. However, the molecular mechanisms underlying this are not fully understood. Since pigment epithelium-derived factor (PEDF) blocks the AGE-signaling pathways, we examined here whether and how PEDF improves insulin resistance in AGE-exposed hepatoma cells, Hep3B cells. Proteins were extracted from Hep3B cells, immunoprecipitated with or without insulin receptor substrate-1 (IRS-1) antibodies, and subjected to Western blot analysis. Glycogen synthesis was measured using [ (14)C]-d-glucose. AGE induced Rac-1 activation and increased phosphorylation of IRS-1 at serine-307 residues, JNK, c-JUN, and IkappaB kinase in association with decreased IkappaB levels in Hep3B cells. PEDF or overexpression of dominant negative Rac-1 blocked these effects of AGE on Hep3B cells. Further, AGEs decreased tyrosine phosphorylation of IRS-1, and subsequently reduced the association of p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by PEDF. Our present study suggests that PEDF could improve the AGE-elicited insulin resistance in Hep3B cells by inhibiting JNK- and IkappaB kinase-dependent serine phosphorylation of IRS-1 via suppression of Rac-1 activation. PEDF may play a protective role against hepatic insulin resistance in diabetes."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.org/dc/terms/identifier"doi:10.1055/s-0028-1083785"xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Nakamura K."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Koga H."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Yoshida T."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Takeuchi M."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Ueno T."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Yamagishi S."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Matsui T."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Imaizumi T."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/author"Sata M."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/name"Horm Metab Res"xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/pages"620-625"xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/title"Pigment epithelium-derived factor (PEDF) ameliorates advanced glycation end product (AGE)-induced hepatic insulin resistance in vitro by suppressing Rac-1 activation."xsd:string
http://purl.uniprot.org/citations/18792873http://purl.uniprot.org/core/volume"40"xsd:string
http://purl.uniprot.org/citations/18792873http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18792873
http://purl.uniprot.org/citations/18792873http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18792873
http://purl.uniprot.org/uniprot/#_A0A140VKF3-mappedCitation-18792873http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18792873
http://purl.uniprot.org/uniprot/#_P45983-mappedCitation-18792873http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18792873
http://purl.uniprot.org/uniprot/#_P36955-mappedCitation-18792873http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18792873
http://purl.uniprot.org/uniprot/P45983http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18792873
http://purl.uniprot.org/uniprot/A0A140VKF3http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18792873
http://purl.uniprot.org/uniprot/P36955http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18792873