β-Cell Glucose Toxicity, Lipotoxicity, and Chronic Oxidative Stress in Type 2 Diabetes

The relentless decline in beta-cell function frequently observed in type 2 diabetic patients, despite optimal drug management, has variously been attributed to glucose toxicity and lipotoxicity. The former theory posits hyperglycemia, an outcome of the disease, as a secondary force that further damages beta-cells. The latter theory suggests that the often-associated defect of hyperlipidemia is a primary cause of beta-cell dysfunction. We review evidence that patients with type 2 diabetes continually undergo oxidative stress, that elevated glucose concentrations increase levels of reactive oxygen species in beta-cells, that islets have intrinsically low antioxidant enzyme defenses, that antioxidant drugs and…

• NI
  National Institutes of Health