Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications

• Published in: The Journal of nutritional biochemistry Vol. 16; no. 12; pp. 705 - 713
• Main Authors: Allen, David A., Yaqoob, Muhammad M., Harwood, Steven M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2005; Elsevier Science
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Associated diseases and complications; biochemical mechanisms; Biological and medical sciences; Caspases - physiology; cell cycle; Cell Cycle - drug effects; Cell-cycle regulators; complications; diabetes; Diabetes Complications - etiology; Diabetes. Impaired glucose tolerance; Diabetic complications; DNA Damage; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; glucose; Glucose - pharmacology; high carbohydrate diet; High glucose-induced apoptosis; Humans; hyperglycemia; Hyperglycemia - complications; hypertrophy; literature reviews; Medical sciences; Mitochondria - physiology; mitogen-activated protein kinase; Mitogen-activated protein kinases; Mitogen-Activated Protein Kinases - physiology; oxidative stress; Oxidative Stress - drug effects; pathogenesis; pathogenesis-related proteins; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - physiology; signal transduction; Tumor Suppressor Protein p53 - physiology; High glucose-induced apoptosis; Cell-cycle regulators; Diabetic complications; Mitogen-activated protein kinases; Endocrinopathy; Human; Oxidative stress; Enzyme; Diabetes mellitus; Diabetic complications: Mitogen-activated protein kinases: Cell-cycle regulators; Cell cycle; Mitogen-activated protein kinase; Complication; Glycemia; Apoptosis
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2005.06.007

Cellular responses to high glucose are numerous and varied but ultimately result in functional changes and, often, cell death. High glucose induces oxidative and nitrosative stress in many cell types causing the generation of species such as superoxide, nitric oxide and peroxynitrite and their derivatives. The role of these species in high glucose-mediated apoptotic cell death is relevant to the complications of diabetes such as neuropathy, nephropathy and cardiovascular disease. High glucose causes activation of several proteins involved in apoptotic cell death, including members of the caspase and Bcl-2 families. These events and the relationship between high glucose-induced oxidative stress and apoptosis are discussed here with reference to additional regulators of apoptosis such as the mitogen-activated protein kinases (MAPKs) and cell-cycle regulators.