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

  1. R. Paul Robertson,
  2. Jamie Harmon,
  3. Phuong Oanh T. Tran and
  4. Vincent Poitout
  1. From the Pacific Northwest Research Institute and the Departments of Medicine and Pharmacology, University of Washington, Seattle, Washington
  1. Address correspondence and reprint requests to R. Paul Robertson, Department of Medicine, University of Washington, 720 Broadway, Seattle, WA 98122. E-mail: rpr{at}


The relentless decline in β-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 β-cells. The latter theory suggests that the often-associated defect of hyperlipidemia is a primary cause of β-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 β-cells, that islets have intrinsically low antioxidant enzyme defenses, that antioxidant drugs and overexpression of antioxidant enzymes protect β-cells from glucose toxicity, and that lipotoxicity, to the extent it can be attributable to hyperlipidemia, occurs only in the context of preexisting hyperglycemia, whereas glucose toxicity can occur in the absence of hyperlipidemia.


  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Les Laboratoires Servier.

    • Accepted March 27, 2003.
    • Received March 4, 2003.
| Table of Contents