Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells
Autor: | Akinori Okumachi, Katsuhiko Ishizaki, Kohtaro Minami, Susumu Seino, Miho Kawaguchi, Toshihiko Iwanaga, Masaaki Okuno, Nobuko Ishizuka, Kazumasa Miyawaki, Kazunobu Oyama |
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Rok vydání: | 2005 |
Předmět: |
Male
medicine.medical_specialty Carbachol medicine.medical_treatment Biology Mice chemistry.chemical_compound Genes Reporter Internal medicine medicine Animals Insulin Cell Lineage Receptor Cells Cultured Chelating Agents chemistry.chemical_classification Multidisciplinary Epidermal Growth Factor Nicotinamide Kinase Gene Expression Profiling Transdifferentiation Cell Differentiation Biological Sciences Pancreas Exocrine In vitro Cell biology Mice Inbred C57BL Enzyme Endocrinology chemistry Dithizone Signal Transduction medicine.drug |
Zdroj: | Proceedings of the National Academy of Sciences. 102:15116-15121 |
ISSN: | 1091-6490 0027-8424 |
Popis: | 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 ≈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 β cells, and that activation of EGF signaling is required in such transdifferentiation. |
Databáze: | OpenAIRE |
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