dc.contributor.author | Hinault, Charlotte | |
dc.contributor.author | Kawamori, Dan | |
dc.contributor.author | Liew, Chong-Wee | |
dc.contributor.author | Maier, Bernhard | |
dc.contributor.author | Hu, Jiang | |
dc.contributor.author | Keller, Susanna R. | |
dc.contributor.author | Mirmira, Raghavendra G. | |
dc.contributor.author | Scrable, Heidi | |
dc.contributor.author | Kulkarni, Rohit Narayan | |
dc.date.accessioned | 2013-02-25T15:27:47Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Hinault, Charlotte, Dan Kawamori, Chong Wee Liew, Bernhard Maier, Jiang Hu, Susanna R. Keller, Raghavendra G. Mirmira, Heidi Scrable, and Rohit N. Kulkarni. 2011. \(\Delta\)40 isoform of p53 controls \(\beta\)-cell proliferation and glucose homeostasis in mice. Diabetes 60(4): 1210-1222. | en_US |
dc.identifier.issn | 0012-1797 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10336927 | |
dc.description.abstract | Objective: Investigating the dynamics of pancreatic \(\beta\)-cell mass is critical for developing strategies to treat both type 1 and type 2 diabetes. p53, a key regulator of the cell cycle and apoptosis, has mostly been a focus of investigation as a tumor suppressor. Although p53 alternative transcripts can modulate p53 activity, their functions are not fully understood. We hypothesized that \(\beta\)-cell proliferation and glucose homeostasis were controlled by \(\Delta\)40p53, a p53 isoform lacking the transactivation domain of the full-length protein that modulates total p53 activity and regulates organ size and life span in mice. Research Design and Methods: We phenotyped metabolic parameters in \(\Delta\)40p53 transgenic (p44tg) mice and used quantitative RT-PCR, Western blotting, and immunohistochemistry to examine \(\beta\)-cell proliferation. Results: Transgenic mice with an ectopic p53 gene encoding \(\Delta\)40p53 developed hypoinsulinemia and glucose intolerance by 3 months of age, which worsened in older mice and led to overt diabetes and premature death from \(\sim\)14 months of age. Consistent with a dramatic decrease in \(\beta\)-cell mass and reduced \(\beta\)-cell proliferation, lower expression of cyclin D2 and pancreatic duodenal homeobox-1, two key regulators of proliferation, was observed, whereas expression of the cell cycle inhibitor p21, a p53 target gene, was increased. Conclusions: These data indicate a significant and novel role for \(\Delta\)40p53 in \(\beta\)-cell proliferation with implications for the development of age-dependent diabetes. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | American Diabetes Association | en_US |
dc.relation.isversionof | doi:10.2337/db09-1379 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064094/pdf/ | en_US |
dash.license | LAA | |
dc.title | \(\Delta\)40 Isoform of p53 Controls \(\beta\)-Cell Proliferation and Glucose Homeostasis in Mice | 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 | 2013-02-25T15:27:47Z | |
dc.identifier.doi | 10.2337/db09-1379 | * |
dash.contributor.affiliated | Liew, Chong-Wee | |
dash.contributor.affiliated | Kulkarni, Rohit | |