β-Cells Are Not Generated in Pancreatic Duct Ligation–Induced Injury in Adult Mice
- Matthew M. Rankin1,
- Christopher J. Wilbur1,
- Kimberly Rak1,
- Emily J. Shields1,
- Anne Granger1 and
- Jake A. Kushner2,3
- 1Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- 2McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Houston, Texas
- 3Texas Children’s Diabetes and Endocrinology Center, Texas Children’s Hospital, Houston, Texas
- Corresponding author: Jake A. Kushner, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0848/-/DC1.
- Received June 24, 2012.
- Accepted January 9, 2013.
- © 2013 by the American Diabetes Association.
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