Show simple item record

dc.contributor.authorTorii, Seiji
dc.contributor.authorSaito, Naoya
dc.contributor.authorKawano, Ayumi
dc.contributor.authorHou, Ni
dc.contributor.authorUeki, Kohjiro
dc.contributor.authorKulkarni, Rohit Narayan
dc.contributor.authorTakeuchi, Toshiyuki
dc.date.accessioned2012-03-23T15:32:39Z
dc.date.issued2009
dc.identifier.citationTorii, Seiji, Naoya Saito, Ayumi Kawano, Ni Hou, Kohjiro Ueki, Rohit N. Kulkarni, and Toshiyuki Takeuchi. 2009. Gene Silencing of Phogrin Unveils Its Essential Role in Glucose-Responsive Pancreatic β-Cell Growth. Diabetes 58(3): 682-692.en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8438177
dc.description.abstractOBJECTIVE—Phogrin and IA-2, autoantigens in insulin-dependent diabetes, have been shown to be involved in insulin secretion in pancreatic β-cells; however, implications at a molecular level are confusing from experiment to experiment. We analyzed biological functions of phogrin in β-cells by an RNA interference technique. RESEARCH DESIGN AND METHODS—Adenovirus-mediated expression of short hairpin RNA specific for phogrin (shPhogrin) was conducted using cultured β-cell lines and mouse islets. Both glucose-stimulated insulin secretion and cell proliferation rate were determined in the phogrin-knockdown cells. Furthermore, protein expression was profiled in these cells. To see the binding partner of phogrin in β-cells, coimmunoprecipitation analysis was carried out. RESULTS—Adenoviral expression of shPhogrin efficiently decreased its endogenous expression in pancreatic β-cells. Silencing of phogrin in β-cells abrogated the glucose-mediated mitogenic effect, which was accompanied by a reduction in the level of insulin receptor substrate 2 (IRS2) protein, without any changes in insulin secretion. Phogrin formed a complex with insulin receptor at the plasma membrane, and their interaction was promoted by high-glucose stimulation that in turn led to stabilization of IRS2 protein. Corroboratively, phogrin knockdown had no additional effect on the proliferation of β-cell line derived from the insulin receptor–knockout mouse. CONCLUSIONS—Phogrin is involved in β-cell growth via regulating stability of IRS2 protein by the molecular interaction with insulin receptor. We propose that phogrin and IA-2 function as an essential regulator of autocrine insulin action in pancreatic β-cells.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.isversionofdoi:10.2337/db08-0970en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646067/pdf/en_US
dash.licenseLAA
dc.titleGene Silencing of Phogrin Unveils Its Essential Role in Glucose-Responsive Pancreatic β-Cell Growthen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalDiabetesen_US
dash.depositing.authorKulkarni, Rohit Narayan
dc.date.available2012-03-23T15:32:39Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.2337/db08-0970*
dash.contributor.affiliatedKulkarni, Rohit


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record