Improved insulin sensitivity is associated with restricted intake of dietary
glycoxidation products in the db/db mouse.
Authors Hofmann SM, Dong HJ, Li Z, Cai W, Altomonte J, Thung SN, Zeng F, Fisher EA,
Vlassara H
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal Diabetes
Year 2002
Date Published 7/1/2002
Volume : Pages 51 : 2082 - 2089
PubMed Reference 12086936
Abstract 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.

Investigators with authorship
Edward FisherNew York University School of Medicine