Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives

Mariyam Khalid, Georg Petroianu, Abdu Adem

Research output: Contribution to journalReview articlepeer-review

182 Citations (Scopus)

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.

Original languageEnglish
Article number542
JournalBiomolecules
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2022
Externally publishedYes

Keywords

  • advanced glycation end products (AGEs)
  • diabetic complications
  • hyperglycemia
  • pancreatic beta cells
  • receptor for advanced glycation end products (RAGE)
  • type 2 diabetes mellitus

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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