title: Molecular control of cell cycle progression in the pancreatic beta-cell.
abstract: Type 1 and type 2 diabetes both result from inadequate production of insulin by the beta-cells of the pancreatic islet. Accordingly, strategies that lead to increased pancreatic beta-cell mass, as well as retained or enhanced function of islets, would be desirable for the treatment of diabetes. Although pancreatic beta-cells have long been viewed as terminally differentiated and irreversibly arrested, evidence now indicates that beta-cells can and do replicate, that this replication can be enhanced by a variety of maneuvers, and that beta-cell replication plays a quantitatively significant role in maintaining pancreatic beta-cell mass and function. Because beta-cells have been viewed as being unable to proliferate, the science of beta-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 beta-cell. In this review, we review the molecular details of cell cycle control as they relate to the pancreatic beta-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 beta-cell replication and improving insulin production in animal models as well as in human pancreatic beta-cells.
authors.affiliation: Division of Endocrinology and Metabolism, BST E-1140, The University of Pittsburgh School of Medicine, 200 Lothrop Street, Pennsylvania 15213, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Cozar-Castellano
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fiaschi-Taesch
authors.forename: Todd A
authors.initials: TA
authors.lastname: Bigatel
authors.forename: Karen K
authors.initials: KK
authors.lastname: Takane
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Ocaña
authors.forename: Rupangi
authors.initials: R
authors.lastname: Vasavada
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D016213:Cyclins / Q000502:physiology; D050684:E2F Transcription Factors / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D000957:Antigens, Viral, Tumor; D016213:Cyclins; D050684:E2F Transcription Factors; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D018844:Cyclin-Dependent Kinases