Intraislet Pancreatic Ducts Can Give Rise to Insulin-Positive Cells
| Autor: | Chiyo Shiota, Shane Fischbach, Krishna Prasadan, Xiangwei Xiao, Christopher Rymer, John Wiersch, Zewen Song, Ping Guo, Yousef El-Gohary, Iljana Gaffar, George K. Gittes, Farzad Esni, Sidhartha Tulachan, Csaba Galambos |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse medicine.medical_specialty Adolescent Transgene medicine.medical_treatment Mice Transgenic Enteroendocrine cell Protein Serine-Threonine Kinases Biology Islets of Langerhans 03 medical and health sciences Pancreatectomy Endocrinology Insulin-Secreting Cells Internal medicine Cadaver medicine Regeneration Animals Humans Insulin Receptor Original Research geography geography.geographical_feature_category Age Factors Receptor Transforming Growth Factor-beta Type II Pancreatic Ducts Infant Islet Mice Mutant Strains Partial Pancreatectomy Luminescent Proteins 030104 developmental biology medicine.anatomical_structure Child Preschool Cell Transdifferentiation Mutant Proteins Female Pancreas Receptors Transforming Growth Factor beta |
| Zdroj: | Endocrinology. 157:166-175 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2015-1175 |
| Popis: | A key question in diabetes research is whether new β-cells can be derived from endogenous, nonendocrine cells. The potential for pancreatic ductal cells to convert into β-cells is a highly debated issue. To date, it remains unclear what anatomical process would result in duct-derived cells coming to exist within preexisting islets. We used a whole-mount technique to directly visualize the pancreatic ductal network in young wild-type mice, young humans, and wild-type and transgenic mice after partial pancreatectomy. Pancreatic ductal networks, originating from the main ductal tree, were found to reside deep within islets in young mice and humans but not in mature mice or humans. These networks were also not present in normal adult mice after partial pancreatectomy, but TGF-β receptor mutant mice demonstrated formation of these intraislet duct structures after partial pancreatectomy. Genetic and viral lineage tracings were used to determine whether endocrine cells were derived from pancreatic ducts. Lineage tracing confirmed that pancreatic ductal cells can typically convert into new β-cells in normal young developing mice as well as in adult TGF-β signaling mutant mice after partial pancreatectomy. Here the direct visual evidence of ducts growing into islets, along with lineage tracing, not only represents strong evidence for duct cells giving rise to β-cells in the postnatal pancreas but also importantly implicates TGF-β signaling in this process. |
| Databáze: | OpenAIRE |
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