Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse.
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.
Hofmann
Susanna M
SM
Brookdale Department of Genetics, Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA. susanna.hofmann@mssm.edu
Dong
Heng-Jiang
HJ
Li
Zhu
Z
Cai
Weijing
W
Altomonte
Jennifer
J
Thung
Swan N
SN
Zeng
Feng
F
Fisher
Edward A
EA
Vlassara
Helen
H
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004032:Diet; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007328:Insulin / Q000032:analysis / Q000502:physiology*; D007677:Kidney Function Tests; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity; D012016:Reference Values
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D017127:Glycation End Products, Advanced; D007328:Insulin; D003847:Deoxyglucose