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Abstract
Background: Protein, lipid, and nucleic acid glycation reactions begin and continue as a result of persistent hyperglycemia in patients with diabetes mellitus. Advanced glycated end products (AGEs) are a complex group of chemical moieties that are formed as a result of the glycation process and play an important role in the pathogenesis of diabetes mellitus. When AGEs interact with their cellular receptor (RAGE), numerous signaling pathways, including nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), are activated, increasing oxidative stress.
Objective: The aim of this review was to summarize in vitro and in vivo studies underlining the involvement of AGEs on beta cell dysfunction and death via oxidative stress.
Methods: A literature search of publications published between 1912 and December 2022 was conducted using MEDLINE, EMBASE, and the Cochrane Library, with restrictions on articles written in English.
Results: Recent insights have revealed that oxidative stress has a crucial role in the development of beta cell dysfunction and insulin resistance, the major hallmarks of type 2 diabetes mellitus. Studies also revealed that AGEs decrease insulin synthesis and secretion in the pancreatic beta cells and induce cell apoptosis.
Conclusion: Experimental data have shown that both AGEs and oxidative stress contribute to beta cell dysfunction and development as well as to the progression of diabetic complications. Many anti- AGE therapies are being developed; however, it remains to be seen whether these therapies can help maintain beta cell function and prevent diabetes complications.
Keywords: Advanced glycation end products, oxidative stress, type 2 diabetes mellitus, reactive oxygen species, insulin resistance, beta cell dysfunction, apoptosis.
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