The role of alpha-to-beta-cell transdifferentiation in beta-cell mass regeneration in adult versus neonatal mice

This study investigated whether pancreatic alpha-to-beta-cell transdifferentiation contributes to beta-cell recovery after a partial beta cell depletion using streptozotocin in either neonatal or adult Glucagon-Cre or Glucagon-CreERT2/Rosa26-eYFP transgenic mice. Pancreas immunofluorescence was performed at 2, 14, and 30 days post-treatment. Lineage tracing of alpha-cells showed increased bi-hormonal (YFP+Ins+Gluc+) and transdifferentiated (YFP+Ins+Gluc-) cells in both age groups following STZ, being highest in neonates. However, the greatest functional recovery was detected in adult females following a glucose tolerance test. Despite increased alpha-to-beta-cell transdifferentiation following STZ, beta-cell abundance did not recover to control levels at either age. The relationship between age and islet cell plasticity was further explored in an observational study through immunofluorescence analysis of human pancreas which revealed that bi-hormonal cells are present in non-diabetic individuals throughout the lifespan. These findings highlight islet cell plasticity that is retained to adulthood and its potential for endogenous regenerative therapies for diabetic patients.