| Transient overexpression of cyclin D2/CDK4/GLP1 genes induces proliferation and differentiation of adult pancreatic progenitors and mediates islet regeneration. | |
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MedLine Citation:
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PMID: 22373529 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The molecular mechanism of β-cell regeneration remains poorly understood. Cyclin D2/CDK4 expresses in normal β cells and maintains adult β-cell growth. We hypothesized that gene therapy with cyclin D2/CDK4/GLP-1 plasmids targeted to the pancreas of STZ-treated rats by ultrasound-targeted microbubble destruction (UTMD) would force cell cycle re-entry of residual G(0)-phase islet cells into G(1)/S phase to regenerate β cells. A single UTMD treatment induced β-cell regeneration with reversal of diabetes for 6 mo without evidence of toxicity. We observed that this β-cell regeneration was not mediated by self-replication of pre-existing β cells. Instead, cyclin D2/CDK4/GLP-1 initiated robust proliferation of adult pancreatic progenitor cells that exist within islets and terminally differentiate to mature islets with β cells and α cells. |
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Authors:
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Shuyuan Chen; Masayuki Shimoda; Jiaxi Chen; Shinichi Matsumoto; Paul A Grayburn |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 11 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-29 Completed Date: 2012-09-14 Revised Date: 2013-04-12 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 695-705 Citation Subset: IM |
Affiliation:
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Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / genetics, physiology Cell Differentiation / genetics, physiology* Cell Proliferation Cyclin D2 / genetics, metabolism* Cyclin-Dependent Kinase 4 / genetics, metabolism* Glucagon-Like Peptide 1 / genetics, metabolism* Immunohistochemistry Insulin-Secreting Cells / cytology*, metabolism* Male Pancreas / cytology* Plasmids Rats Stem Cells / cytology*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P02 DK58398/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclin D2; 89750-14-1/Glucagon-Like Peptide 1; EC 2.7.11.22/Cyclin-Dependent Kinase 4 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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