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

The existence of adult beta-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that beta-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 beta-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to beta-cell mass expansion. Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of beta-cell content via traditional morphometry methodologies that superficially sample the pancreas. To overcome this potential bias, we quantified beta-cells from the entire pancreas and observed that beta-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 beta-cell lineage. Thus, we conclude that beta-cells are not generated in injured adult mouse pancreas. Diabetes 62:1634-1645, 2013