Advanced Glycation End Products and Inflammation in Type 1 Diabetes Development

Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which the β-cells of the pancreas are attacked by the host’s immune system, ultimately resulting in hyperglycemia. It is a complex multifactorial disease postulated to result from a combination of genetic and environmental factors. In parallel with increasing prevalence of T1D in genetically stable populations, highlighting an environmental component, consumption of advanced glycation end products (AGEs) commonly found in in Western diets has increased significantly over the past decades. AGEs can bind to cell surface receptors including the receptor for advanced glycation end products (RAGE). RAGE has proinflammatory roles including in host–pathogen defense, thereby influencing immune cell behavior and can activate and cause proliferation of immune cells such as islet infiltrating CD8+ and CD4+ T cells and suppress the activity of T regulatory cells, contributing to β-cell injury and hyperglycemia. Insights from studies of individuals at risk of T1D have demonstrated that progression to symptomatic onset and diagnosis can vary, ranging from months to years, providing a window of opportunity for prevention strategies. Interaction between AGEs and RAGE is believed to be a major environmental risk factor for T1D and targeting the AGE-RAGE axis may act as a potential therapeutic strategy for T1D prevention.

The analgesic effects of insulin and its disorders in streptozotocin‐induced short‐term diabetes

“…The formation of AGEs by reactive di‐carbonyls has been shown to play a key role in the pathogenesis of sensory neuron damage (El‐Mesallamy et al., 2011; Jack & Wright, 2012; Singh et al., 2014). Long‐term hyperglycemia in type 1 diabetes mellitus (T1DM) leads to increased expression of receptors for RAGE and accelerates the formation of RAGE ligands, including AGEs (Du et al., 2022; Khalid et al., 2022; Le Bagge et al., 2020). Insulin treatment reduces the activation of ROS and AGEs, and the expression levels of RAGE in diabetic rats.…”

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren’s syndrome

“…This perpetuates a proinflammatory cycle associated with chronic inflammation in autoimmune diseases, further contributing to tissue damage and disease progressionc. [50,51]…”

“…This perpetuates a proinflammatory cycle associated with chronic inflammation in autoimmune diseases, further contributing to tissue damage and disease progressionc. [50,51] HIF-1 signaling pathway is key in regulating various immune components and inflammation. It modulates the function of T cells, neutrophils, dendritic cells, and other immune cells within the immune system.…”

Molecular mechanisms of Tangningtongluo Tablet in the treatment of diabetes based on network pharmacology and bioinformatics

“…The interaction between AGEs and their receptor RAGE can lead to β-cell dysfunction. One possible therapeutic approach to stop T1DM could be to target the AGE-RAGE axis [30,31]; the expression of IL-17…”