Studies focus on understanding insulin-producing beta-cell origins through transgenic mouse generation. Three main research areas: determination of cell fates, establishment of islet cell lineages, and differentiation/regeneration potential of adult pancreatic cells. The Cre/loxP system tags endocrine progenitor cells in vivo to mark precursor or hormone-producing cells through site-specific recombination. Cell fate decisions in early pancreatic primordia involve cell autonomous and non-autonomous signals. Adult pancreata regeneration potential is studied using transgenic mice where specific pancreatic cell types can be conditionally ablated. Recent findings show extreme beta-cell loss in adult mice is followed by spontaneous beta-cell regeneration, primarily through conversion of adult glucagon-producing alpha-cells into insulin-producers. A limited number of alpha-cells suffices to prevent major metabolic deregulation under basal conditions in adult mice.