The replication of beta cells in normal physiology, in disease and for therapy

Abstract

Replication of beta cells is an important source of beta-cell expansion in early childhood. The recent linkage of type 2 diabetes with several transcription factors involved in cell cycle regulation implies that growth of the beta-cell mass in early childhood might be an important determinant of risk for type 2 diabetes. Under some circumstances, including obesity and pregnancy, the beta-cell mass is adaptively increased in adult humans. The mechanisms by which this adaptive growth occurs and the relative contributions of beta-cell replication or of mechanisms independent of beta-cell replication are unknown. Also, although there is interest in the potential for beta-cell regeneration as a therapeutic approach in both type 1 and 2 diabetes, little is yet known about the potential sources of new beta cells in adult humans. In common with other cell types, replicating beta cells have an increased vulnerability to apoptosis, which is likely to limit the therapeutic value of inducing beta-cell replication in the proapoptotic environment of type 1 and 2 diabetes unless applied in conjunction with a strategy to suppress increased apoptosis.