β-Cells Are Not Generated in Pancreatic Duct Ligation–Induced Injury in Adult Mice

  1. Jake A. Kushner2,3
  1. 1Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
  2. 2McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Houston, Texas
  3. 3Texas Children’s Diabetes and Endocrinology Center, Texas Children’s Hospital, Houston, Texas
  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 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.

Footnotes

  • Received June 24, 2012.
  • Accepted January 9, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

| Table of Contents

This Article

  1. Diabetes vol. 62 no. 5 1634-1645
  1. Supplementary Data
  2. All Versions of this Article:
    1. db12-0848v1
    2. db12-0848v2
    3. 62/5/1634 most recent