Fetal or Neonatal Low-Glycotoxin Environment Prevents Autoimmune Diabetes in NOD Mice

Abstract

Advanced glycation end products (AGEs) are implicated in ␤-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 ⑀ -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 GADand insulin-responsive interferon (IFN)-␥-positive Tcells from H-AGE mice (P

Advanced Glycation End Products (Ages) in Food: Focusing on Mediterranean Pasta

“…Positive correlation between dAGE content and serum/tissue AGE levels have been also confirmed by several animal study [17,27,28]. For example Peppa et al [29] to assess the role of dAGEs on type 1 diabetes, exposed the genetically susceptible NOD mice to a high-AGE diet and to a nutritionally similar diet with approximate fivefold-lower levels of CML and MG and demonstrated that after 44 weeks of treatment, NOD mice fed with Low-AGE diet showed almost half of serum AGE levels respect to High-AGE diet fed NOD mice. Moreover, Urribari et al [30] demonstrated that dAGEs were correlated to the excess serum AGE levels found in diabetics and renal failure patients, contributing markedly to the total AGE pool in the body [11][12][13].…”

Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes

“…There is increasing evidence to suggest that AGEs also promote beta cell dysfunction [12,13]. Furthermore, a reduced incidence of diabetes in a mouse model of autoimmune diabetes, the NOD mouse (NODLt) [14], has been reported following dietary restriction of AGEs. However, the specific mechanisms whereby insulin secretory pathways are damaged by AGEs are not known.…”

Involvement of advanced glycation end products in the pathogenesis of diabetic complications: the protective role of regular physical activity

“…These results support the concept that diabetes is a disease characterised by the acceleration of the degenerative chemical mechanisms associated with biological aging; namely, the disease affects tissue proteins with long life span by the formation of AGEs and by enhanced oxidative stress. The highest AGEs concentrations resulted from both enhanced endogenous synthesis and diet, and can also be directly implicated in the oxidative stress and damage induced on the beta cells of the pancreatic Langerhans islets in diabetic patients [100].…”