Molecular Control of Cell Cycle Progression in the Pancreatic ß-Cell
Irene Cozar-Castellano,
Nathalie Fiaschi-Taesch,
Todd A. Bigatel,
Karen K. Takane,
Adolfo Garcia-Ocaña,
Rupangi Vasavada and
Andrew F. Stewart
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 productionof insulin by the ß-cells of the pancreatic islet.Accordingly, strategies that lead to increased pancreatic ß-cellmass, as well as retained or enhanced function of islets, wouldbe desirable for the treatment of diabetes. Although pancreaticß-cells have long been viewed as terminally differentiatedand irreversibly arrested, evidence now indicates that ß-cellscan and do replicate, that this replication can be enhancedby a variety of maneuvers, and that ß-cell replicationplays a quantitatively significant role in maintaining pancreaticß-cell mass and function.
Because ß-cells have been viewed as being unable toproliferate, the science of ß-cell replication isundeveloped. In the past several years, however, this has begunto change at a rapid pace, and many laboratories are now focusedon elucidating the molecular details of the control of cellcycle in the ß-cell. In this review, we review themolecular details of cell cycle control as they relate to thepancreatic ß-cell. Our hope is that this review canserve as a common basis and also a roadmap for those interestedin developing novel strategies for enhancing ß-cellreplication and improving insulin production in animal modelsas well as in human pancreatic ß-cells.
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