| Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. | |
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MedLine Citation:
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PMID: 16210247 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although several studies have suggested that insulin-secreting cells can be generated in vitro from cells residing in adult exocrine pancreas, neither the origin of these cells nor their precise insulin secretory properties was obtained. We show here that insulin-secreting cells can be derived from adult mouse pancreatic exocrine cells by suspension culture in the presence of EGF and nicotinamide. The frequency of insulin-positive cells was only 0.01% in the initial preparation and increased to approximately 5% in the culture conditions. Analysis by the Cre/loxP-based direct cell lineage tracing system indicates that these newly made cells originate from amylase/elastase-expressing pancreatic acinar cells. Insulin secretion is stimulated by glucose, sulfonylurea, and carbachol, and potentiation by glucagon-like peptide-1 also occurs. Insulin-containing secretory granules are present in these cells. In addition, we found that the enzymatic dissociation of pancreatic acini itself leads to activation of EGF signaling, and that inhibition of EGF receptor kinase blocks the transdifferentiation. These data demonstrate that pancreatic acinar cells can transdifferentiate into insulin-secreting cells with secretory properties similar to those of native pancreatic beta cells, and that activation of EGF signaling is required in such transdifferentiation. |
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Authors:
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Kohtaro Minami; Masaaki Okuno; Kazumasa Miyawaki; Akinori Okumachi; Katsuhiko Ishizaki; Kazunobu Oyama; Miho Kawaguchi; Nobuko Ishizuka; Toshihiko Iwanaga; Susumu Seino |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-10-06 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 102 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-10-20 Completed Date: 2005-12-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 15116-21 Citation Subset: IM |
Affiliation:
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Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation / physiology Cell Lineage* Cells, Cultured Chelating Agents / metabolism Dithizone / metabolism Epidermal Growth Factor / metabolism Gene Expression Profiling Genes, Reporter Insulin / metabolism* Male Mice Mice, Inbred C57BL Pancreas, Exocrine / cytology*, physiology Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Chelating Agents; 11061-68-0/Insulin; 60-10-6/Dithizone; 62229-50-9/Epidermal Growth Factor |
| Comments/Corrections | |
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