The Development of Diabetes in E2f1/E2f2 Mutant Mice Reveals Important Roles for Bone Marrow-Derived Cells in Preventing Islet Cell Loss
Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance. Pancreatic exocrine cells in E2f1/E2f2 mutant mice become increasi...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2003-10, Vol.100 (22), p.12935-12940 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Li, Feng X. Zhu, Jing W. Tessem, Jeffery S. Beilke, Joshua Varella-Garcia, Marileila Jensen, Jan Hogan, Christopher J. DeGregori, James |
| description | Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance. Pancreatic exocrine cells in E2f1/E2f2 mutant mice become increasingly polyploid with age, coinciding with severe exocrine atrophy. Furthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes with high penetrance. Surprisingly, transplantation of wild-type bone marrow can prevent or rescue diabetes in E2f1-/-E2f2-/-mice. We hypothesize that exocrine degeneration results in a destructive environment for beta cells, which can be alleviated by restoration of the hematopoietic system that is also defective in E2f1-/-E2f2-/-mice. The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients. |
| doi_str_mv | 10.1073/pnas.2231861100 |
| format | Article |
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Pancreatic exocrine cells in E2f1/E2f2 mutant mice become increasingly polyploid with age, coinciding with severe exocrine atrophy. Furthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes with high penetrance. Surprisingly, transplantation of wild-type bone marrow can prevent or rescue diabetes in E2f1-/-E2f2-/-mice. We hypothesize that exocrine degeneration results in a destructive environment for beta cells, which can be alleviated by restoration of the hematopoietic system that is also defective in E2f1-/-E2f2-/-mice. The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2231861100</identifier><identifier>PMID: 14566047</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Beta cells ; Biological Sciences ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Bone marrow ; Bone Marrow Cells - physiology ; Bone Marrow Transplantation ; Cell Cycle Proteins ; Diabetes ; Diabetes complications ; Diabetes Mellitus - genetics ; Diabetes Mellitus - pathology ; Diabetes Mellitus - therapy ; DNA-Binding Proteins ; E2F Transcription Factors ; E2F1 protein ; E2F1 Transcription Factor ; E2F2 protein ; Exocrine cells ; Female ; Insulin ; Insulin - therapeutic use ; Islet cells ; Islets of Langerhans - pathology ; Male ; Medical research ; Mice ; Mice, Knockout ; Pancreas ; Pancreatic cells ; Polyploidy ; Sex Characteristics ; Transcription Factors - deficiency ; Transcription Factors - genetics ; Transplantation, Homologous ; Type 1 diabetes mellitus</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2003-10, Vol.100 (22), p.12935-12940</ispartof><rights>Copyright 1993-2003 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 28, 2003</rights><rights>Copyright © 2003, The National Academy of Sciences 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-a534b75611b3260ac88722e1c5089d07e4c1d53991d4ad927952831e9f4f5e23</citedby><cites>FETCH-LOGICAL-c526t-a534b75611b3260ac88722e1c5089d07e4c1d53991d4ad927952831e9f4f5e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/100/22.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3148064$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3148064$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14566047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Feng X.</creatorcontrib><creatorcontrib>Zhu, Jing W.</creatorcontrib><creatorcontrib>Tessem, Jeffery S.</creatorcontrib><creatorcontrib>Beilke, Joshua</creatorcontrib><creatorcontrib>Varella-Garcia, Marileila</creatorcontrib><creatorcontrib>Jensen, Jan</creatorcontrib><creatorcontrib>Hogan, Christopher J.</creatorcontrib><creatorcontrib>DeGregori, James</creatorcontrib><title>The Development of Diabetes in E2f1/E2f2 Mutant Mice Reveals Important Roles for Bone Marrow-Derived Cells in Preventing Islet Cell Loss</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance. 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The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients.</description><subject>Animals</subject><subject>Beta cells</subject><subject>Biological Sciences</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - physiology</subject><subject>Bone Marrow Transplantation</subject><subject>Cell Cycle Proteins</subject><subject>Diabetes</subject><subject>Diabetes complications</subject><subject>Diabetes Mellitus - genetics</subject><subject>Diabetes Mellitus - pathology</subject><subject>Diabetes Mellitus - therapy</subject><subject>DNA-Binding Proteins</subject><subject>E2F Transcription Factors</subject><subject>E2F1 protein</subject><subject>E2F1 Transcription Factor</subject><subject>E2F2 protein</subject><subject>Exocrine cells</subject><subject>Female</subject><subject>Insulin</subject><subject>Insulin - therapeutic use</subject><subject>Islet cells</subject><subject>Islets of Langerhans - pathology</subject><subject>Male</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Pancreas</subject><subject>Pancreatic cells</subject><subject>Polyploidy</subject><subject>Sex Characteristics</subject><subject>Transcription Factors - deficiency</subject><subject>Transcription Factors - genetics</subject><subject>Transplantation, Homologous</subject><subject>Type 1 diabetes mellitus</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2P0zAQhiMEYsvCmQtCFgckDtnO-COJDxygXaBSK9Cqd8tNJrup0rjYSYF_wM_G_dAWuOzFljzP-86HJ0leIlwh5GK87Wy44lxgkSECPEpGCBrTTGp4nIwAeJ4WksuL5FkIawDQqoCnyQVKlWUg81Hye3lHbEo7at12Q13PXM2mjV1RT4E1HbvmNY7jwdli6G2ML5qS2E0U2Daw2Wbr_OH5xrVRUDvPPrqO2MJ6736kU_LNjio2obY92H3zUdn1TXfLZqGl_hBhcxfC8-RJHS3pxem-TJafrpeTL-n86-fZ5MM8LRXP-tQqIVe5it2uBM_AlkWRc05YKih0BTnJEisltMZK2krzXCteCCRdy1oRF5fJ-6PtdlhtqCpjMd62ZuubjfW_jLON-TfSNXfm1u0MlxATRf3bk9677wOF3myaUMYmbEduCCZHwRVK_SCImkut9B588x-4doPv4gwMB5QAmcIIjY9Q6eOsPNX3FSOY_SaY_SaY8yZExeu_Gz3zp6-PwLsTsFee7SC6GORaKFMPbdvTzz6y7AE2Iq-OyDr0zt8zAmUBmRR_AJRn0Ag</recordid><startdate>20031028</startdate><enddate>20031028</enddate><creator>Li, Feng X.</creator><creator>Zhu, Jing W.</creator><creator>Tessem, Jeffery S.</creator><creator>Beilke, Joshua</creator><creator>Varella-Garcia, Marileila</creator><creator>Jensen, Jan</creator><creator>Hogan, Christopher J.</creator><creator>DeGregori, James</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20031028</creationdate><title>The Development of Diabetes in E2f1/E2f2 Mutant Mice Reveals Important Roles for Bone Marrow-Derived Cells in Preventing Islet Cell Loss</title><author>Li, Feng X. ; 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Pancreatic exocrine cells in E2f1/E2f2 mutant mice become increasingly polyploid with age, coinciding with severe exocrine atrophy. Furthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes with high penetrance. Surprisingly, transplantation of wild-type bone marrow can prevent or rescue diabetes in E2f1-/-E2f2-/-mice. We hypothesize that exocrine degeneration results in a destructive environment for beta cells, which can be alleviated by restoration of the hematopoietic system that is also defective in E2f1-/-E2f2-/-mice. The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>14566047</pmid><doi>10.1073/pnas.2231861100</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Beta cells Biological Sciences Blood Glucose - drug effects Blood Glucose - metabolism Bone marrow Bone Marrow Cells - physiology Bone Marrow Transplantation Cell Cycle Proteins Diabetes Diabetes complications Diabetes Mellitus - genetics Diabetes Mellitus - pathology Diabetes Mellitus - therapy DNA-Binding Proteins E2F Transcription Factors E2F1 protein E2F1 Transcription Factor E2F2 protein Exocrine cells Female Insulin Insulin - therapeutic use Islet cells Islets of Langerhans - pathology Male Medical research Mice Mice, Knockout Pancreas Pancreatic cells Polyploidy Sex Characteristics Transcription Factors - deficiency Transcription Factors - genetics Transplantation, Homologous Type 1 diabetes mellitus |
| title | The Development of Diabetes in E2f1/E2f2 Mutant Mice Reveals Important Roles for Bone Marrow-Derived Cells in Preventing Islet Cell Loss |
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