Biochemical basis and clinical consequences of glucolipotoxicity: a primer

Heart Fail Clin. 2012 Oct;8(4):501-11. doi: 10.1016/j.hfc.2012.06.011.


Both glucose and fatty acids may have good/adaptive or toxic/maladaptive actions on the pancreatic beta cell, depending on their concentrations. Hyperglycemia, via metabolic intermediates, may result in multiple cellular effects that are toxic to the pancreatic beta cell and indeed other tissues. While free fatty acids may affect cellular processes beyond lipid metabolism by interacting with transcription factors, triglyceride rich lipoproteins are endothelial cell-toxic and facilitate atherogenesis. The paradigm of "glucolipotoxicity" espouses that increased glucose and fatty acid levels act synergistically in causing toxicity to pancreatic islets and other organs, a process that eventually leads to the multiple defects seen in the metabolic syndrome and diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Chronic Disease
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / pathology
  • Fatty Acids, Nonesterified / metabolism
  • Glucose Intolerance
  • Heart / physiopathology*
  • Heart Diseases / metabolism*
  • Heart Diseases / pathology
  • Humans
  • Hyperglycemia
  • Hyperlipidemias / complications*
  • Hyperlipidemias / pathology
  • Insulin Resistance*
  • Insulin-Secreting Cells / pathology*
  • Reactive Oxygen Species


  • Fatty Acids, Nonesterified
  • Reactive Oxygen Species