Fetal or neonatal low-glycotoxin environment prevents autoimmune diabetes in NOD mice

Diabetes. 2003 Jun;52(6):1441-8. doi: 10.2337/diabetes.52.6.1441.


Advanced glycation end products (AGEs) are implicated in beta-cell oxidant stress. Diet-derived AGE (dAGE) are shown to contribute to end-organ toxicity attributed to diabetes. To assess the role of dAGE on type 1 diabetes, NOD mice were exposed to a high-AGE diet (H-AGE) and to a nutritionally similar diet with approximate fivefold-lower levels of N(epsilon)-carboxymethyllysine (CML) and methylglyoxal-derivatives (MG) (L-AGE). Suppression of serum CML and MG in L-AGE-fed mice was marked by suppression of diabetes (H-AGE mice >94% vs. L-AGE mice 33% in founder [F](0), 14% in F(1), and 13% in F(2) offspring, P < 0.006) and by a delay in disease onset (4-month lag). Survival for L-AGE mice was 76 vs. 0% after 44 weeks of H-AGE mice. Reduced insulitis in L-AGE versus H-AGE mice (P < 0.01) was marked by GAD- and insulin-unresponsive pancreatic interleukin (IL)-4-positive CD4+ cells compared with the GAD- and insulin-responsive interferon (IFN)-gamma-positive T-cells from H-AGE mice (P < 0.005). Splenocytes from L-AGE mice consisted of GAD- and insulin-responsive IL-10-positive CD4+ cells compared with the IFN-gamma-positive T-cells from H-AGE mice (P < 0.005). Therefore, high AGE intake may provide excess antigenic stimulus for T-cell-mediated diabetes or direct beta-cell injury in NOD mice; both processes are ameliorated by maternal or neonatal exposure to L-AGE nutrition.

Publication types

  • Case Reports

MeSH terms

  • Administration, Oral
  • Aging
  • Albuminuria
  • Animals
  • Animals, Newborn
  • Blood Glucose / metabolism
  • Creatinine / urine
  • Crosses, Genetic
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Glycation End Products, Advanced / administration & dosage
  • Glycation End Products, Advanced / pharmacology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology
  • Lysine / analogs & derivatives*
  • Lysine / analysis
  • Male
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Pyruvaldehyde / analysis


  • Blood Glucose
  • Glycation End Products, Advanced
  • N(6)-carboxymethyllysine
  • Pyruvaldehyde
  • Creatinine
  • Lysine