Determinants of pancreatic β-cell regeneration

Recent studies have revealed a surprising plasticity of pancreatic β-cell mass. β-cell mass is now recognized to increase and decrease in response to physiological demand, for example during pregnancy and in insulin-resistant states. Moreover, we and others have shown that mice recover spontaneously from diabetes induced by killing of 70-80% of β-cells, by β-cell regeneration. The major cellular source for new β-cells following specific ablation, as well as during normal homeostatic maintenance of adult β-cells, is proliferation of differentiated β-cells. More recently, it was shown that one form of severe pancreatic injury, ligation of the main pancreatic duct, activates a population of embryonic-type endocrine progenitor cells, which can differentiate into new β-cells. The molecular triggers for enhanced β-cell proliferation during recovery from diabetes and for activation of embryonic-type endocrine progenitors remain unknown and represent key challenges for future research. Taken together, recent data suggest that regenerative therapy for diabetes may be a realistic goal.