Cell Biochemistry and Biophysics

, Volume 48, Issue 2, pp 139–146

Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in Type 2 diabetes


    • Pacific Northwest Research Institute
  • Huarong Zhou
    • Pacific Northwest Research Institute
  • Tao Zhang
    • Pacific Northwest Research Institute
  • Jamie S. Harmon
    • Pacific Northwest Research Institute
Original Paper

DOI: 10.1007/s12013-007-0026-5

Cite this article as:
Robertson, R.P., Zhou, H., Zhang, T. et al. Cell Biochem Biophys (2007) 48: 139. doi:10.1007/s12013-007-0026-5


Type 2 diabetes is characterized by a relentless decline in pancreatic islet beta cell function and worsening hyperglycemia despite optimal medical treatment. Our central hypothesis is that residual hyperglycemia, especially after meals, generates reactive oxygen species (ROS), which in turn causes chronic oxidative stress on the beta cell. This hypothesis is supported by several observations. Exposure of isolated islets to high glucose concentrations induces increases in intracellular peroxide levels. The beta cell has very low intrinsic levels of antioxidant proteins and activities and thus is very vulnerable to ROS. Treatment with antioxidants protects animal models of type 2 diabetes against complete development of phenotypic hyperglycemia. The molecular mechanisms responsible for the glucose toxic effect on beta cell function involves disappearance of two important regulators of insulin promoter activity, PDX-1 and MafA. Antioxidant treatment in vitro prevents disappearance of these two transcription factors and normalizes insulin gene expression. These observations suggest that the ancillary treatment with antioxidants may improve outcomes of standard therapy of type 2 diabetes in humans.


Oxidative stressGlucose toxicityBeta cell

Copyright information

© Humana Press Inc. 2007