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β-Cell Growth: An Unusual Paradigm of Organogenesis That is Cyclin D2/cdk4 Dependent

Jake A. Kushner

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Improved understanding of the signals that regulate growth and maintenance of adult ?-cells is remains one of the main questions in diabetes research. However, new advances in identifying the specific components involved in G1 cell cycle progression of ?-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 ?-cell growth. Our observations complement previous data regarding cdk4, and suggest that mitogenic signals act via this pathway to influence acquisition of adult ?-cell mass. Although cyclin D2/cdk4 activity is critically important for ?-cell growth, it was unclear how much ongoing replication is required to maintain ?-cell mass. Recent long-term ?-cell labeling studies reveal that adult ?-cells could conceivably live for the life of the organism. This new paradigm of long-lived ?-cells challenges previous notions of rapid turnover of adult ?-cell mass. Thus, much remains to be learned in order to expand adult ?-cell mass in diabetes patients.

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.