Advanced glycation end products induce skeletal muscle atrophy and insulin resistance via activating ROS-mediated ER stress PERK/FOXO1 signaling
Haixia Du, Yanpeng Ma, Xiqiang Wang, Yong Zhang, Ling Zhu, Shuang Shi, Shuo Pan, Zhongwei Liu
Abstract
In this study, we proposed a molecular mechanism underlying the skeletal muscle atrophy-associated insulin resistance in type 2 diabetes mellitus (T2DM). Our investigation suggests that exposure to AGEs, which are characteristic metabolites of T2DM pathology, induces the activation of reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, leading to the upregulation of the protein kinase RNA-like ER kinase (PERK)/forkhead box O1 (FOXO1)/muscle atrophy F-box pathway and subsequent skeletal muscle atrophy, ultimately resulting in insulin resistance.
Topics & Concepts
Insulin resistanceDownregulation and upregulationFOXO1Endoplasmic reticulumGlycationAtrophyUnfolded protein responseInsulin receptorInternal medicineSkeletal muscleMuscle atrophyEndocrinologyOxidative stressKinaseCell biologyChemistryMedicineProtein kinase BInsulinDiabetes mellitusSignal transductionBiologyBiochemistryGeneAdipose Tissue and MetabolismMuscle Physiology and DisordersAutophagy in Disease and Therapy