Beta Cells Are Not Generated in Pancreatic Duct Ligation Induced Injury in Adult Mice

  1. Jake A. Kushner
  1. Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Division of Endocrinology and Diabetes, Philadelphia, Pennsylvania, United States
  2. Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Division of Endocrinology and Diabetes, Philadelphia, Pennsylvania, United States
  3. Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Division of Endocrinology and Diabetes, Philadelphia, Pennsylvania, United States
  4. Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Division of Endocrinology and Diabetes, Philadelphia, Pennsylvania, United States
  5. Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Division of Endocrinology and Diabetes, Philadelphia, Pennsylvania, United States
  6. Baylor College of Medicine, Pediatric Diabetes and Endocrinology, 6701 Fannin Street, Suite 1020, Houston, Texas, United States
  1. Corresponding author: Jake A. Kushner, kushner{at}bcm.edu

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, which 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 ductal 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 analogues, 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.

  • Received June 24, 2012.
  • Accepted January 7, 2013.

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