TY - JOUR
T1 - Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products
AU - Zheng, Feng
AU - He, Cijiang
AU - Cai, Weijing
AU - Hattori, Masakazu
AU - Steffes, Michael
AU - Vlassara, Helen
PY - 2002
Y1 - 2002
N2 - Background. Reactive advanced glycation end products (AGEs), known to promote diabetic tissue damage, occur endogenously as well as in heated foods and are orally absorbed. The relative contribution of diet-derived AGEs to diabetic nephropathy (DN) remains unclear. Methods. We tested a standard mouse food (AIN-93G) found to be rich in AGEs (H-AGE diet) in parallel with a similar diet that contained six-fold lower AGE content (L-AGE), but equal calories, macromitrients, and micronutrients. Non-obese diabetic mice (NOD) with type I diabetes (TID) and db/db mice with type 2 diabetes (T2D) were randomly assigned to each formula for either 4 or 11 months, during which time renal parameters and AGE levels were assessed. Results. Compared to the progressive DN and short survival seen in NOD mice exposed to long-term H-AGE feeding, L-AGE-fed NOD mice developed minimal glomerular pathology and a modest increase in urinary albumin: creatinine ratio (p<0.005), and a significantly extended survival (p<0.0001), consistent with lower serum (p<0.025) and kidney AGEs (p<0.01). Also, in the 4-month study, and in contrast to the H-AGE-fed mice, L-A*E-fed NOD and dbldb mice exhibited low levels of renal cortex TGFfl-1 (p < 0.05), laminin 131 rnRNA (p < 0.01) and )cl IV collagen mRNA (p < 0.05) and protein, in concert with reduced serum and kidney AGEs (p < 0.05, respectively). Conclusion. Intake of high-level, food-derived AGEs is a major contributor to DN in T1D and T21) mice. Avoidance of dietary AGEs provides sustained protection against DN in mice; providing the rationale for similar studies in human diabetic patients.
AB - Background. Reactive advanced glycation end products (AGEs), known to promote diabetic tissue damage, occur endogenously as well as in heated foods and are orally absorbed. The relative contribution of diet-derived AGEs to diabetic nephropathy (DN) remains unclear. Methods. We tested a standard mouse food (AIN-93G) found to be rich in AGEs (H-AGE diet) in parallel with a similar diet that contained six-fold lower AGE content (L-AGE), but equal calories, macromitrients, and micronutrients. Non-obese diabetic mice (NOD) with type I diabetes (TID) and db/db mice with type 2 diabetes (T2D) were randomly assigned to each formula for either 4 or 11 months, during which time renal parameters and AGE levels were assessed. Results. Compared to the progressive DN and short survival seen in NOD mice exposed to long-term H-AGE feeding, L-AGE-fed NOD mice developed minimal glomerular pathology and a modest increase in urinary albumin: creatinine ratio (p<0.005), and a significantly extended survival (p<0.0001), consistent with lower serum (p<0.025) and kidney AGEs (p<0.01). Also, in the 4-month study, and in contrast to the H-AGE-fed mice, L-A*E-fed NOD and dbldb mice exhibited low levels of renal cortex TGFfl-1 (p < 0.05), laminin 131 rnRNA (p < 0.01) and )cl IV collagen mRNA (p < 0.05) and protein, in concert with reduced serum and kidney AGEs (p < 0.05, respectively). Conclusion. Intake of high-level, food-derived AGEs is a major contributor to DN in T1D and T21) mice. Avoidance of dietary AGEs provides sustained protection against DN in mice; providing the rationale for similar studies in human diabetic patients.
KW - Advanced glycation
KW - Animal models
KW - Diabetic complication
KW - Food
KW - Kidney
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U2 - 10.1002/dmrr.283
DO - 10.1002/dmrr.283
M3 - Article
C2 - 12112941
AN - SCOPUS:0035985243
SN - 1520-7552
VL - 18
SP - 224
EP - 237
JO - Diabetes/Metabolism Research and Reviews
JF - Diabetes/Metabolism Research and Reviews
IS - 3
ER -