| http://purl.uniprot.org/citations/18930714 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18930714 | http://www.w3.org/2000/01/rdf-schema#comment | "Using various biochemical, pharmacological and molecular biological approaches, we have recently reported regulatory roles for Rac1, a small G-protein, in glucose-stimulated insulin secretion (GSIS). However, little is understood with respect to localization of, and regulation by, specific regulatory factors of Rac1 in GSIS. Herein, we investigated regulatory roles for Tiam1, a specific nucleotide exchange factor (GEF) for Rac1, in GSIS in pancreatic beta-cells. Western blot analysis indicated that Tiam1 is predominantly cytosolic in distribution. NSC23766, a specific inhibitor of Tiam1-mediated activation of Rac1, markedly attenuated glucose-induced, but not KCl-induced insulin secretion in INS 832/13 cells and normal rat islets. Further, NSC23766 significantly reduced glucose-induced activation (i.e. GTP-bound form) and membrane association of Rac1 in INS 832/13 cells and rat islets. Moreover, siRNA-mediated knock-down of Tiam1 markedly inhibited glucose-induced membrane trafficking and activation of Rac1 in INS 832/13 cells. Interestingly, however, in contrast to the inhibitory effects of NSC23766, Tiam1 gene depletion potentiated GSIS in these cells; such a potentiation of GSIS was sensitive to extracellular calcium. Together, our studies present the first evidence for a regulatory role for Tiam1/Rac1-sensitive signaling step in GSIS. They also provide evidence for the existence of a potential Rac1/Tiam1-independent, but calcium-sensitive component for GSIS in these cells."xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bcp.2008.09.021"xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/author | "McDonald P."xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/author | "Olson L.K."xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/author | "Kowluru A."xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/author | "Veluthakal R."xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/author | "Madathilparambil S.V."xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/name | "Biochem Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/pages | "101-113"xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/title | "Regulatory roles for Tiam1, a guanine nucleotide exchange factor for Rac1, in glucose-stimulated insulin secretion in pancreatic beta-cells."xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://purl.uniprot.org/core/volume | "77"xsd:string |
| http://purl.uniprot.org/citations/18930714 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18930714 |
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