Document Detail


Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells.
MedLine Citation:
PMID:  16210247     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-06
Journal Detail:
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:
Created Date:  2005-10-20     Completed Date:  2005-12-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15116-21     Citation Subset:  IM    
Affiliation:
Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Chelating Agents; 11061-68-0/Insulin; 60-10-6/Dithizone; 62229-50-9/Epidermal Growth Factor
Comments/Corrections

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