Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications

Nat Clin Pract Endocrinol Metab. 2008 May;4(5):285-93. doi: 10.1038/ncpendmet0786. Epub 2008 Mar 11.


Many important biochemical mechanisms are activated in the presence of high levels of glucose, which occur in diabetes. Elevated levels of glucose accelerate the formation of advanced glycation end-products (AGEs). Via their chief signaling receptor-the AGE-specific receptor (commonly abbreviated as RAGE)-AGEs generate reactive oxygen species and activate inflammatory signaling cascades. Consequently, AGEs have key roles in the pathogenesis of diabetic complications. Two discoveries have advanced our knowledge of the roles of RAGE in inflammation. First, this receptor has multiple ligands and binds not only AGEs but also proinflammatory, calcium-binding S100 proteins (also known as calgranulins) and nuclear high mobility group protein box-1. Second, RAGE is expressed on T lymphocytes, monocytes and macrophages; RAGE expression on T lymphocytes is essential for effective priming of immune responses in vivo. In this Review, we chronicle roles for RAGE in the pathogenesis of diabetic complications and develop the hypothesis that, in addition to RAGE's central role in the inflammatory response, it is critically linked to the pathogenesis of types 1 and 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Diabetes Complications / metabolism*
  • Glycation End Products, Advanced / metabolism*
  • Humans
  • Inflammation / metabolism
  • Mice
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism*


  • Glycation End Products, Advanced
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic