Advanced glycation end-products: modifiable environmental factors profoundly mediate insulin resistance

Abstract

Advanced glycation end-products are toxic by-products of metabolism and are also acquired from high-temperature processed foods. They promote oxidative damage to proteins, lipids and nucleotides. Aging and chronic diseases are strongly associated with markers for oxidative stress, especially advanced glycation end-products, and resistance to peripheral insulin-mediated glucose uptake. Modifiable environmental factors including high levels of refined and simple carbohydrate diets, hypercaloric diets and sedentary lifestyles drive endogenous formation of advanced glycation end-products via accumulation of highly reactive glycolysis intermediates and activation of the polyol/aldose reductase pathway producing high intracellular fructose. High advanced glycation end-products overwhelm innate defenses of enzymes and receptor-mediated endocytosis and promote cell damage via the pro-inflammatory and pro-oxidant receptor for advanced glycation end-products. Oxidative stress disturbs cell signal transduction, especially insulin-mediated metabolic responses. Here we review emerging evidence that restriction of dietary advanced glycation end-products significantly reduces total systemic load and insulin resistance in animals and humans in diabetes, polycystic ovary syndrome, healthy populations and dementia. Of clinical importance, this insulin sensitizing effect is independent of physical activity, caloric intake and adiposity level.

Dietary iron intake, iron status, and gestational diabetes

“…Yet the possibility of unmeasured residual confounding cannot be ruled out as data on heme iron were mostly based on observational studies. For example, nitrites and other preservatives in processed meat, as well as advanced glycation end products formed during the high-temperature cooking of animal-derived foods, have been shown to contribute to insulin resistance (72)(73)(74). Findings on dietary nonheme iron intakes and iron supplement are inconclusive in general.…”

Dietary fat quantity and quality modifies advanced glycation end products metabolism in patients with metabolic syndrome

“…Recent studies show the contribution of advanced glycation end products (AGEs) in the origin and progression of certain chronic diseases, as well as MetS . AGEs are a group of prooxidant and cytotoxic compounds, derived from the nonenzymatic glycation of proteins, lipids, and nuclear acids via a complex sequence of reactions referred as the Maillard reaction .…”

Assessment of the Concentration of Advanced Glycation End Products in Traditional Chinese Foods

“…Likewise, lipids initiate the formation of free radicals by lipid peroxidation, and therefore they are a significant contributor to AGE formation (Rizzi ; Ottum et al . ). However, comparing the CML content of the food items with similar ingredients, we found that although The CML content was related to the type of ingredients, there was not necessarily a connection between one specific ingredient and the CML level, as shown in Fig.…”

“…Consequently, a diet rich in protein and carbohydrate causes higher concentrations of AGEs (CML or AGE-fl), and high quantities of AGE-modified proteins were produced with increasing temperature (Uribarri and Tuttle 2006;Frolov et al 2014). Likewise, lipids initiate the formation of free radicals by lipid peroxidation, and therefore they are a significant contributor to AGE formation (Rizzi 2003;Ottum et al 2015). However, comparing the CML content of the food items with similar ingredients, we found that although The CML content was related to the type of ingredients, there was not necessarily a connection between one specific ingredient and the CML level, as shown in Fig.…”