DNA damage does not cause brdu labeling of mouse or human β-cells Academic Article uri icon


MeSH Major

  • Hyperglycemia
  • Hyperinsulinism


  • Pancreatic β-cell regeneration, the therapeutic expansion of β-cell number to reverse diabetes, is an important goal. Replication of differentiated insulin-producing cells is the major source of new β-cells in adult mice and juvenile humans. Nucleoside analogs such as BrdU, which are incorporated into DNA during S-phase, have been widely used to quantify β-cell proliferation. However, reports of β-cell nuclei labeling with both BrdU and γ-phosphorylated H2A histone family member X (γH2AX), a DNA damage marker, have raised questions about the fidelity of BrdU to label S-phase, especially during conditions when DNA damage is present. We performed experiments to clarify the causes of BrdU-γH2AX double labeling in mouse and human β-cells. BrdU-γH2AX colabeling is neither an age-related phenomenon nor limited to human β-cells. DNA damage suppressed BrdU labeling and BrdU-γH2AX colabeling. In dispersed islet cells, but not in intact islets or in vivo, pro-proliferative conditions promoted both BrdU and γH2AX labeling, which could indicate DNA damage, DNA replication stress, or cell cycle-related intrinsic H2AX phosphorylation. Strategies to increase β-cell number must not only tackle the difficult challenge of enticing a quiescent cell to enter the cell cycle, but also achieve safe completion of the cell division process.

publication date

  • January 2019



  • Academic Article



  • eng

PubMed Central ID

  • PMC6477907

Digital Object Identifier (DOI)

  • 10.2337/db18-0761

PubMed ID

  • 30833468

Additional Document Info

start page

  • 975

end page

  • 987


  • 68


  • 5