Improved Insulin Sensitivity Is Associated With Restricted Intake of Dietary Glycoxidation Products in the db/db Mouse

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 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 ϳ13% 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.

Diabetic threesome (hyperglycaemia, renal function and nutrition) and advanced glycation end products: evidence for the multiple-hit agent?

“…Rats on a high-AGE diet have been reported to show a higher increase in plasma AGE, urinary excretion of AGE, weight gain, renal protein excretion and renal expression of the pro-fibrotic cytokine transforming growth factor b (129) , while, increased fasting plasma insulin has been detected in mice (130) . Similar findings have been obtained in studies of mice with diabetes (non-obese or db/db) fed a high-AGE diet (higher plasma AGE, weight gain and fasting plasma insulin) (131) , as well as in another study in which there was also progressive development of diabetic nephropathy (higher urinary AGE excretion, renal protein excretion, glomerular hypertrophy, mesangial expansion and expression of transforming growth factor b) and shorter survival (non-obese NOD mice) (132) . A low-AGE diet has also been found to delay the onset of diabetes in diabetic (NOD) mice (133) , improve wound healing in db/db mice (134) and delay the progression of atherosclerosis (135) .…”

Processed meat intake and incidence of Type 2 diabetes in younger and middle-aged women

“…Here, animal models and human studies suggest that AGE could be involved in the progression of Type 2 diabetes. The development of Type 2 diabetes was reduced by treatment with aminoguanidine, an AGE inhibitor, in genetically diabetic mice [48] and improvement of various features of insulin resistance was shown in mice fed a diet low in AGE [49]. In addition, a diet high in AGE was found to promote inflammatory mediators that might be important in the genesis of diabetes, such as vascular adhesion molecule-1, tumour necrosis factor-alpha, and C-reactive protein, in a study among 24 diabetic subjects [50].…”

Soft Drink Consumption Linked with Fatty Liver in the Absence of Traditional Risk Factors

“…Also, regarding obesity and aspartame, formaldehyde converted from the free methyl alcohol accumulates in the cells and damages mitochondrial DNA, with most toxicity effects occurring in the liver. Finally, the effect of caramel colourant has been incriminated as a cause of elevated liver enzymes and may be a potential source of advanced glycation end product, which may promote insulin resistance and can be proinflammatory (5,6,20). The extent to which fructose, aspartame and caramel contributed to severe fatty liver could not be concluded due to the small size of the cohort.…”

“…Recent evidence suggests that sugar-sweetened soft drink consumption is associated with the risk of obesity and diabetes because they contain large amounts of high-fructose corn syrup (HFCS), which raises blood glucose similarly to sucrose (4). In addition, soft drinks contain caramel colouring, which is rich in advanced glycation end products that might increase insulin resistance and inflammation (4)(5)(6).…”