Beta-cell growth: an unusual paradigm of organogenesis that is cyclin D2/Cdk4 dependent.
Improved understanding of the signals that regulate growth and maintenance of adult beta-cells remains one of the main challenges in diabetes research. However, new advances in identifying the specific components involved in G1 cell cycle progression of beta-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 beta-cell growth. Our observations complement previous data regarding cdk4, and suggest that mitogenic signals could act via this pathway to influence acquisition of adult beta-cell mass. Although cyclin D2/cdk4 activity is critically important for beta-cell growth, it was unclear how much ongoing replication is required to maintain beta-cell mass. Our recent long-term beta-cell labeling studies reveal that adult beta-cells could conceivably live for the life of the organism. This new paradigm of long-lived beta-cells challenges previous notions of rapid turnover of adult beta-cell mass. Thus, much remains to be learned in order to expand adult beta-cell mass in diabetes patients.
Kushner
Jake A
JA
Children's Hospital of Philadelphia, Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. kushnerj@mail.med.upenn.edu
D000375:Aging; D000818:Animals; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D056742:Cyclin D2; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D038081:Organogenesis; D010179:Pancreas / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D019938:Cyclin D1; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4