β-Cells Are Not Generated in Pancreatic Duct Ligation–Induced Injury in Adult Mice
-
- Matthew M. Rankin
- Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
-
- Christopher J. Wilbur
- Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
-
- Kimberly Rak
- Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
-
- Emily J. Shields
- Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
-
- Anne Granger
- Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
-
- Jake A. Kushner
- McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Houston, Texas
説明
<jats:p>The existence of adult β-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that β-cell progenitors can be activated by ductal ligation–induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional β-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to β-cell mass expansion. Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of β-cell content via traditional morphometry methodologies that superficially sample the pancreas. To overcome this potential bias, we quantified β-cells from the entire pancreas and observed that β-cell mass and insulin content are totally unchanged by PDL-induced injury. Lineage-tracing studies using sequential administration of thymidine analogs, rat insulin 2 promoter–driven cre-lox, and low-frequency ubiquitous cre-lox reveal that PDL does not convert progenitors to the β-cell lineage. Thus, we conclude that β-cells are not generated in injured adult mouse pancreas.</jats:p>
収録刊行物
-
- Diabetes
-
Diabetes 62 (5), 1634-1645, 2013-04-16
American Diabetes Association
