β-cell growth: An unusual paradigm of organogenesis that is cyclin D2/Cdk4 dependent

Abstract

Improved understanding of the signals that regulate growth and maintenance of adult β-cells remains one of the main challenges in diabetes research. However, new advances in identifying the specific components involved in G 1 cell cycle progression of β-cells suggest that the molecular determinants of this pathway could ultimately be revealed. We find that cyclin D2, and to a minor degree cyclin D1, are required for adult β-cell growth. Our observations complement previous data regarding cdk4, and suggest that mitogenic signals could act via this pathway to influence acquisition of adult β-cell mass. Although cyclin D2/cdk4 activity is critically important for β-cell growth, it was unclear how much ongoing replication is required to maintain β-cell mass. Our recent long-term β-cell labeling studies reveal that adult β-cells could conceivably live for the life of the organism. This new paradigm of long-lived β-cells challenges previous notions of rapid turnover of adult β-cell mass. Thus, much remains to be learned in order to expand adult β-cell mass in diabetes patients. ©2006 Landes Bioscience.