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Diabetes. 2013 May;62(5):1634-45. doi: 10.2337/db12-0848. Epub 2013 Jan 24.

β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.

Author information

1
Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Abstract

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.

PMID:
23349489
PMCID:
PMC3636617
DOI:
10.2337/db12-0848
[Indexed for MEDLINE]
Free PMC Article
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