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Cited by 879

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Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives

Open access
Khalid, Mariyam, Petroianu, Georg, Adem, Abdu·2022·Biomolecules

Abstract

Persistent hyperglycemic state in type 2 diabetes mellitus leads to the initiation and progression of non-enzymatic glycation reaction with proteins and lipids and nucleic acids. Glycation reaction leads to the generation of a heterogeneous group of chemical moieties known as advanced glycated end products (AGEs), which play a central role in the pathophysiology of diabetic complications. The engagement of AGEs with its chief cellular receptor, RAGE, activates a myriad of signaling pathways such as MAPK/ERK, TGF-β, JNK, and NF-κB, leading to enhanced oxidative stress and inflammation. The downstream consequences of the AGEs/RAGE axis involve compromised insulin signaling, perturbation of metabolic homeostasis, RAGE-induced pancreatic beta cell toxicity, and epigenetic modifications. The AGEs/RAGE signaling instigated modulation of gene transcription is profoundly associated with the progression of type 2 diabetes mellitus and pathogenesis of diabetic complications. In this review, we will summarize the exogenous and endogenous sources of AGEs, their role in metabolic dysfunction, and current understandings of AGEs/RAGE signaling cascade. The focus of this review is to recapitulate the role of the AGEs/RAGE axis in the pathogenesis of type 2 diabetes mellitus and its associated complications. Furthermore, we present an overview of future perspectives to offer new therapeutic interventions to intervene with the AGEs/RAGE signaling pathway and to slow down the progression of diabetes-related complications.

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Metadata

Authors
Khalid, M., Petroianu, G., & Adem, A.
Venue
Biomolecules
Publisher
MDPI AG
Published
2022-04-04
Volume
12
Issue
4
Pages
542
ISSN
2218-273X (ISSN-L)
OpenAlex
W4224307827
Cited by
879
References
25
FWCI
83.57
Type
journal article
Language
en
Open access
gold

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