Abstract
The term glycotoxins includes the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds, such as methylglyoxal (MG). Glycotoxins were initially thought to participate in the development of diabetic complications because of their increased formation from glucose. However, they also form and accumulate in tissues since the early stages of disease, such as metabolically unhealthy obesity and prediabetes. Such accumulation has been suggested to result from dysregulated activity of detoxification systems, such as the glyoxalase system, as well as increased dietary consumption, namely from high-glucose and high-fructose foods processed at high temperatures. Although some studies may have used supraphysiological doses, in vitro systems and animal models have shown glycotoxin-induced insulin resistance. Moreover, dietary glycotoxin restriction was shown to improve insulin resistance in humans and glyoxalase (GLO)-1 upregulation improved insulin sensitivity and metabolic function. This review summarizes the current knowledge about glycotoxin involvement in the development of insulin resistance, the mechanisms involved and the usefulness of GLO-1 modulation, and a possible therapeutic strategy to improve insulin sensitivity.
Highlights
The term glycotoxins includes the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds, such as methylglyoxal (MG)
We have shown that MG accumulation impairs adipose tissue response to hypoxia, leading to higher activation of inflammatory pathways, but insulin resistance was only observed in an experimental model of adipose tissue ischemia [62]
Such observations suggest a link with early stages of metabolic dysregulation such as prediabetes and avoiding the classical idea of glycosative stress being a consequence of chronic hyperglycemia [73,75]
Summary
The term glycotoxins includes the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds, such as methylglyoxal (MG). Some findings in lean animal models were controversial because of the high doses used, insulin resistance was consistently observed in obese animal models with increased glycosative stress, while AGE-restricted diets have been shown to improve insulin sensitivity in normal, overweight, and diabetic patients (reviewed by [1]). Such mechanisms may contribute to the progressive deterioration of metabolic homeostasis observed in metabolic syndrome/prediabetes and later in type 2 diabetes. The sections will discuss the impact of glycotoxins on the mechanisms governing insulin secretion and sensitivity
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have