β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.
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.
Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Matthew M
MM
Rankin
Christopher J
CJ
Wilbur
Kimberly
K
Rak
Emily J
EJ
Shields
Anne
A
Granger
Jake A
JA
Kushner
D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D003433:Crosses, Genetic; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008026:Ligation; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010183:Pancreatic Ducts / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D007328:Insulin; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C407737:Neurog3 protein, mouse