α-Cells are dispensable in postnatal morphogenesis and maturation of mouse pancreatic islets

Glucagon-producing alpha-cells are the second-most abundant cell type in the islet. Whereas alpha-cells make up less than 20% of the cells in a mature mouse islet, they occupy a much larger proportion of the pancreatic endocrine cell population during the early postnatal period, the time when morphological and functional maturation occurs to form adult islets. To determine whether alpha-cells have a role in postnatal islet development, a diphtheria toxin-mediated alpha-cell ablation mouse model was established. Rapid and persistant depletion of alpha-cells was achieved by daily injection of the toxin for 2 wk starting at postnatal day 1 (P1). Total pancreatic glucagon content in the alpha-cell-ablated mice was undetectable at P14 and still less than 0.3% of that of the control mice at 4 mo of age. Histological analyses revealed that formation of spherical islets occurred normally, and the islet size distribution was not changed despite the near-total lack of alpha-cells. Furthermore, there were no differences in expression of beta-cell maturation marker proteins, including urocortin 3 and glucose transporter 2, in the alpha-cell-ablated islets at P14. Mice lacking alpha-cells grew normally and appeared healthy. Both glucose and insulin tolerance tests demonstrated that the alpha-cell-ablated mice had normal glucose homeostasis. These results indicate that alpha-cells do not play a critical role in postnatal islet morphogenesis or functional maturation of beta-cells.