title: Too many breaks (brakes): pancreatic β-cell senescence leads to diabetes.
abstract: Pancreatic β-cells regulate glucose homeostasis by secreting insulin in response to metabolic demands. The generation of these adult endocrine cells predominantly occurs through self-replication rather than through differentiation from their stem-cell progenitors; therefore, regulating cellular division through the cell cycle machinery is an essential component of this process. Arrest of the pancreatic β-cell cycle, which abolishes this replication capability, results in an inability to meet the metabolic demand for insulin, disrupting glucose homeostasis collectively driving type 2 diabetes mellitus-the most common metabolic disease worldwide. Therefore, the purpose of this review is to highlight how upstream cell cycle transcriptional regulators, direct cell cycle modulators, and external stress factors such as DNA damage and genomic instability, influence β-cell replication. We specifically highlight and compare recent animal models created to understand β-cell hyperplasia and hypoplasia as well as offer some insight into potential diabetic therapies.
authors.affiliation: Department of Immunology, The Graduate School of Biomedical Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Tavana
authors.forename: Chengming
authors.initials: C
authors.lastname: Zhu
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D016922:Cellular Senescence; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000473:pathology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases