Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse

Diabetes. 2002 Jul;51(7):2082-9. doi: 10.2337/diabetes.51.7.2082.


Advanced glycation end products (AGEs), known promoters of diabetic complications, form abundantly in heated foods and are ingested in bioreactive forms. To test whether dietary AGEs play a role in the progression of insulin resistance, C57/BL/KsJ db/db mice were randomly placed for 20 weeks on a diet with either a low AGE content (LAD) or a 3.4-fold higher content of AGE (high AGE diet [HAD]), including (epsilon)N-carboxymethyllysine (CML) and methylglyoxal (MG). LAD-fed mice showed lower fasting plasma insulin levels throughout the study (P = 0.01). Body weight was reduced by approximately 13% compared with HAD-fed mice (P = 0.04) despite equal food intake. LAD-fed mice exhibited significantly improved responses to both glucose (at 40 min, P = 0.003) and insulin (at 60 min, P = 0.007) tolerance tests, which correlated with a twofold higher glucose uptake by adipose tissue (P = 0.02). Compared with the severe hypertrophy and morphological disorganization of islets from HAD-fed mice, LAD-fed mice presented a better-preserved structure of the islets. LAD-fed mice demonstrated significantly increased plasma HDL concentrations (P < 0.0001). Consistent with these observations, LAD-fed mice exhibited twofold lower serum CML and MG concentrations compared with HAD-fed mice (P = 0.02). These results demonstrate that reduced AGE intake leads to lower levels of circulating AGE and to improved insulin sensitivity in db/db mice.

Publication types

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

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Biological Transport
  • Blood Glucose / metabolism*
  • Body Weight
  • Deoxyglucose / pharmacokinetics*
  • Diabetes Mellitus / physiopathology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diet*
  • Dietary Carbohydrates / metabolism*
  • Disease Models, Animal
  • Glucose Tolerance Test
  • Glycation End Products, Advanced / metabolism*
  • Insulin / analysis
  • Insulin / physiology*
  • Kidney Function Tests
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Obesity*
  • Reference Values


  • Blood Glucose
  • Dietary Carbohydrates
  • Glycation End Products, Advanced
  • Insulin
  • Deoxyglucose