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Molecular Control of Cell Cycle Progression in the Pancreatic ß-Cell

Division of Endocrinology, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213

Correspondence: Address all correspondence and requests for reprints to: Andrew F. Stewart, M.D., Chief, Division of Endocrinology and Metabolism, BST E-1140, The University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213. E-mail: stewart{at}dom.pitt.edu

Type 1 and type 2 diabetes both result from inadequate production of insulin by the ß-cells of the pancreatic islet. Accordingly, strategies that lead to increased pancreatic ß-cell mass, as well as retained or enhanced function of islets, would be desirable for the treatment of diabetes. Although pancreatic ß-cells have long been viewed as terminally differentiated and irreversibly arrested, evidence now indicates that ß-cells can and do replicate, that this replication can be enhanced by a variety of maneuvers, and that ß-cell replication plays a quantitatively significant role in maintaining pancreatic ß-cell mass and function.

Because ß-cells have been viewed as being unable to proliferate, the science of ß-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 ß-cell. In this review, we review the molecular details of cell cycle control as they relate to the pancreatic ß-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 ß-cell replication and improving insulin production in animal models as well as in human pancreatic ß-cells.

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