The NOTCH pathway in β-cell growth and differentiation.

Beta-cell replacement represents the optimal therapy for type 1 diabetes. Efforts to manipulate β-cell proliferation and differentiation could be advanced by a better understanding of the normal pathways regulating β-cell development and renewal. NOTCH signaling is a highly conserved pathway which plays a central role in pancreas development. Cell-lineage tracing has revealed the reactivation of the NOTCH pathway in adult human β cells cultured under conditions which induce cell proliferation and dedifferentiation. Inhibition of NOTCH signaling in dedifferentiated cells following ex vivo expansion has been shown to promote restoration of the β-cell phenotype. This approach may increase the availability of functional β cells for transplantation.