title: Apoptosis of beta cells in diabetes mellitus.
abstract: Diabetes mellitus is a multifactorial metabolic disorder characterized by hyperglycemia. Apoptosis in beta cells has been observed in response to diverse stimuli, such as glucose, cytokines, free fatty acids, leptin, and sulfonylureas, leading to the activation of polyol, hexosamine, and diacylglycerol/protein kinase-C (DAG/PKC) pathways that mediate oxidative and nitrosative stress causing the release of different cytokines. Cytokines induce the expression of Fas and tumor necrosis factor-alpha (TNF-α) by activating the transcription factor, nuclear factor-κb, and signal transducer and activator of transcription 1 (STAT-1) in the β cells in the extrinsic pathway of apoptosis. Cytokines produced in beta cells also induce proapoptotic members of the intrinsic pathway of apoptosis. The genetic alterations in apoptosis signaling machinery and the pathogenesis of diabetes include Fas, FasL, Akt, caspases, calpain-10, and phosphatase and tensin homolog (Pten). The other gene products that are involved in diabetes are nitric oxide synthase-2 (NOS2), small ubiquitin-like modifier (SUMO), apolipoprotein CIII (ApoCIII), forkhead box protein O1 (FOXO1), and Kruppel-like zinc finger protein Gli-similar 3 (GLIS3). The gene products having antiapoptotic nature are Bcl-2 and Bcl-XL. Epigenetic mechanisms play an important role in type I and type II diabetes. Further studies on the apoptotic genes and gene products in diabetics may be helpful in pharmacogenomics and individualized treatment along with antioxidants targeting apoptosis in diabetes.
authors.affiliation: Department of Genetics, Osmania University , Hyderabad, India .
authors.forename: Rachakatla
authors.initials: R
authors.lastname: Anuradha
authors.forename: Mudigonda
authors.initials: M
authors.lastname: Saraswati
authors.forename: Kishore G
authors.initials: KG
authors.lastname: Kumar
authors.forename: Surekha H
authors.initials: SH
authors.lastname: Rani
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents