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© 2002 by the American Diabetes Association, Inc.
Gastrin Stimulates ß-Cell Neogenesis and Increases Islet Mass From Transdifferentiated but Not From Normal Exocrine Pancreas Tissue
From the Cell Differentiation Group, Diabetes Research Center, Free University of Brussels (VUB), Brussels, Belgium
It is still unclear which factors regulate pancreatic regeneration and ß-cell neogenesis and which precursor cells are involved. We evaluated the role of intravenously infused gastrin in regenerating pancreas of duct-ligated rats. The ligation of exocrine ducts draining the splenic half of the pancreas resulted in acinoductal transdifferentiation within the ligated part but not in the unligated part. We found that infusion of gastrin from day 7 to 10 postligation resulted in a doubling of the ß-cell mass in the ligated part as measured by morphometry. This increase in insulin-expressing cells was not associated with increased proliferation, hypertrophy, or reduced cell death of the ß-cells. Furthermore, we found an increased percentage of single, extra-insular ß-cells and small ß-cell clusters induced by gastrin infusion. These changes occurred only in the ligated part of the pancreas, where transdifferentiation of the exocrine acinar cells to ductlike cells (metaplasia) had occurred, and was not found in the normal unaffected pancreatic tissue. In conclusion, we demonstrate that administration of gastrin stimulates ß-cell neogenesis and expansion of the ß-cell mass from transdifferentiated exocrine pancreas.
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