dc.contributor.author | Torii, Seiji | |
dc.contributor.author | Saito, Naoya | |
dc.contributor.author | Kawano, Ayumi | |
dc.contributor.author | Hou, Ni | |
dc.contributor.author | Ueki, Kohjiro | |
dc.contributor.author | Kulkarni, Rohit Narayan | |
dc.contributor.author | Takeuchi, Toshiyuki | |
dc.date.accessioned | 2012-03-23T15:32:39Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | Torii, 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.issn | 0012-1797 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:8438177 | |
dc.description.abstract | OBJECTIVE—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.iso | en_US | en_US |
dc.publisher | American Diabetes Association | en_US |
dc.relation.isversionof | doi:10.2337/db08-0970 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646067/pdf/ | en_US |
dash.license | LAA | |
dc.title | Gene Silencing of Phogrin Unveils Its Essential Role in Glucose-Responsive Pancreatic β-Cell Growth | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | Diabetes | en_US |
dash.depositing.author | Kulkarni, Rohit Narayan | |
dc.date.available | 2012-03-23T15:32:39Z | |
dash.affiliation.other | HMS^Medicine-Brigham and Women's Hospital | en_US |
dc.identifier.doi | 10.2337/db08-0970 | * |
dash.contributor.affiliated | Kulkarni, Rohit | |