Molecular control of cell cycle progression in the pancreatic β-cell

Type 1 and type 2 diabetes both result from inadequate production of insulin by the β-cells of the pancreatic islet. Accordingly, strategies that lead to increased pancreatic β-cell mass, as well as retained or enhanced function of islets, would be desirable for the treatment of diabetes. Although pancreatic β-cells have long been viewed as terminally differentiated and irreversibly arrested, evidence now indicates that β-cells can and do replicate, that this replication can be enhanced by a variety of maneuvers, and that β-cell replication plays a quantitatively significant role in maintaining pancreatic β-cell mass and function. Because β-cells have been viewed as being unable to proliferate, the science of β-cell replication is undeveloped. In the past several years, however, this has begun to change at a rapid pace, and many laboratories are now focused on elucidating the molecular details of the control of cell cycle in the β-cell. In this review, we review the molecular details of cell cycle control as they relate to the pancreatic β-cell. Our hope is that this review can serve as a common basis and also a roadmap for those interested in developing novel strategies for enhancing β-cell replication and improving insulin production in animal models as well as in human pancreatic β-cells.