Cell cycle control of pancreatic beta cell proliferation.
Diabetes mellitus ensues as a consequence of the body's inability to respond normally to high blood glucose levels. The onset of diabetes is due to several pathological changes, which are a reflection of either the inability of the pancreatic beta cells to secrete sufficient insulin to combat the hyperglycemia or a state of insulin resistance in target tissues. However, the significance of changes in beta cell mass and decreased beta cell proliferation or growth in progression of diabetes has been under-appreciated. Beta cells, like all other cells of our body are under the regulatory checks and balances enforced by changes in cell cycle progression. However, very little is known regarding the key components of the cell cycle machinery regulating cell cycle control of beta cells. Knowledge of key elements involved in cell cycle regulation of beta cells will go a long way in improving our understanding of the replication capacity and developmental biology of beta cells. This information is essential for us to design new approaches that can be used to correct beta cell deficiency in diabetes. This review focuses on the current knowledge of factors important for proliferation of beta cells and proposes a cell cycle model for regeneration of the beta cell population lost or reduced in diabetes.
Rane
S G
SG
Fels Institute For Cancer Research And Molecular Biology, Temple University, School Of Medicine, 3307 North Broad Street. Philadelphia, PA 19140, USA. sushilrane@hotmail.com
Reddy
E P
EP
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D003920:Diabetes Mellitus / Q000473:pathology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction
D016213:Cyclins; D007328:Insulin; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases