Advanced glycation end products attenuate cellular insulin sensitivity by increasing the generation of intracellular reactive oxygen species in adipocytes

Diabetes Res Clin Pract. 2007 May;76(2):236-44. doi: 10.1016/j.diabres.2006.09.016. Epub 2006 Nov 13.


Advanced glycation end products (AGE) have been observed in various pathological conditions especially in diabetes mellitus. However, it is unclear as to whether AGE are involved in insulin resistance in adipose tissues. In this study, we examined the effects of AGE on insulin sensitivity in adipocytes by examining the effects of AGE and its mechanisms on the glucose uptake in adipocytes and adipocyte differentiation. Glucose-, glyceraldehyde-, or glycolaldehyde-derived AGE inhibited the differentiation of 3T3-L1 cells. These AGE also inhibited the glucose uptake in the absence or presence of insulin, which were completely prevented by antibody against AGE or receptor for AGE (RAGE). The AGE increased the intracellular reactive oxygen species (ROS) generation in 3T3-L1 adipocytes, and the effects of AGE on glucose uptake were completely reversed by the treatment with an anti-oxidant, N-acetylcysteine. The AGE also induced the expression of monocyte chemoattractant protein-1, which has been implicated in the development of obesity-associated glucose intolerance, in 3T3-L1 adipocytes. Our present study suggests that AGE-RAGE interaction inhibits the glucose uptake through the overgeneration of intracellular ROS, thus indicating that it is involved in the development of obesity-related insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / pharmacology
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Biological Transport / drug effects
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Deoxyglucose / metabolism
  • Deoxyglucose / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Glucose / chemistry
  • Glucose / metabolism
  • Glycation End Products, Advanced / chemistry
  • Glycation End Products, Advanced / metabolism
  • Glycation End Products, Advanced / pharmacology*
  • Glyceraldehyde / chemistry
  • Glyceraldehyde / metabolism
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Mice
  • Reactive Oxygen Species / metabolism*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Glycation End Products, Advanced
  • Insulin
  • Reactive Oxygen Species
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Glyceraldehyde
  • N-Acetylcysteinamide
  • Deoxyglucose
  • Glucose
  • Acetylcysteine