scholarly journals AGEs-Induced and Endoplasmic Reticulum Stress/Inflammation-Mediated Regulation of GLUT4 Expression and Atherogenesis in Diabetes Mellitus

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
Marisa Passarelli ◽  
Ubiratan Fabres Machado
Keyword(s):  
Diabetes Mellitus ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Glucose Transporter ◽  
Current Knowledge ◽  
Advanced Glycation ◽  
Inflammatory Stress ◽  
Glut4 Expression ◽  
Glycation End Products ◽  
Solute Carrier

In recent decades, complex and exquisite pathways involved in the endoplasmic reticulum (ER) and inflammatory stress responses have been demonstrated to participate in the development and progression of numerous diseases, among them diabetes mellitus (DM). In those pathways, several players participate in both, reflecting a complicated interplay between ER and inflammatory stress. In DM, ER and inflammatory stress are involved in both the pathogenesis of the loss of glycemic control and the development of degenerative complications. Furthermore, hyperglycemia increases the generation of advanced glycation end products (AGEs), which in turn refeed ER and inflammatory stress, contributing to worsening glycemic homeostasis and to accelerating the development of DM complications. In this review, we present the current knowledge regarding AGEs-induced and ER/inflammation-mediated regulation of the expression of GLUT4 (solute carrier family 2, facilitated glucose transporter member 4), as a marker of glycemic homeostasis and of cardiovascular disease (CVD) development/progression, as a leading cause of morbidity and mortality in DM.

scholarly journals Advanced glycation end products induce a prothrombotic phenotype in mice via interaction with platelet CD36

Blood ◽  
2012 ◽  
Vol 119 (25) ◽  
pp. 6136-6144 ◽  
Author(s):  
Weifei Zhu ◽  
Wei Li ◽  
Roy L. Silverstein
Keyword(s):  
Diabetes Mellitus ◽  
Mouse Models ◽  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Drug Induced ◽  
Glycation End Products ◽  
End Products

Abstract Diabetes mellitus has been associated with platelet hyperreactivity, which plays a central role in the hyperglycemia-related prothrombotic phenotype. The mechanisms responsible for this phenomenon are not established. In the present study, we investigated the role of CD36, a class-B scavenger receptor, in this process. Using both in vitro and in vivo mouse models, we demonstrated direct and specific interactions of platelet CD36 with advanced glycation end products (AGEs) generated under hyperglycemic conditions. AGEs bound to platelet CD36 in a specific and dose-dependent manner, and binding was inhibited by the high-affinity CD36 ligand NO2LDL. Cd36-null platelets did not bind AGE. Using diet- and drug-induced mouse models of diabetes, we have shown that cd36-null mice had a delayed time to the formation of occlusive thrombi compared with wild-type (WT) in a FeCl3-induced carotid artery injury model. Cd36-null mice had a similar level of hyperglycemia and a similar level of plasma AGEs compared with WT mice under this condition, but WT mice had more AGEs incorporated into thrombi. Mechanistic studies revealed that CD36-dependent JNK2 activation is involved in this prothrombotic pathway. Therefore, the results of the present study couple vascular complications in diabetes mellitus with AGE-CD36–mediated platelet signaling and hyperreactivity.

Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease

2018 ◽  
Vol 475 (6) ◽  
pp. 1037-1057 ◽  
Author(s):  
Alex B. Addinsall ◽  
Craig R. Wright ◽  
Sof Andrikopoulos ◽  
Chris van der Poel ◽  
Nicole Stupka
Keyword(s):  
Metabolic Disease ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Metabolic Dysfunction ◽  
Iodothyronine Deiodinase ◽  
Inflammatory Stress ◽  
Cellular Stress Responses

Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.

Glycation End-Products and their Receptors: Pathophysiology and Therapeutic Targeting in Diabetes Mellitus

2021 ◽  
Vol 1 ◽  
pp. 19-35
Author(s):  
Hussein Saad Alzadi ◽  
Naza Mohammed Ali Mahmood
Keyword(s):  
Diabetes Mellitus ◽  
Signaling Pathway ◽  
Cellular Metabolism ◽  
Fragility Fractures ◽  
Clinical Results ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Soluble Rage ◽  
Glycation End Products ◽  
End Products

Diabetes mellitus (DM) compromises cell metabolism and function in many organs, resulting in increased risks of complications in many organs such as kidney, nervous system, eye, and fragility fractures. Advanced glycation end products (AGEs) are chemical moieties produced during long-term hyperglycemia; they interact with the specific receptors for AGEs (RAGEs) and make a meaningful contribution to cellular metabolism and/or alteration of their functions. Searches in PubMed using the keywords "advanced glycation end product "RAGE", "sRAGE", "DM", and "complications” were made to reveal some of the clinical outcomes of DM in cellular metabolism and organ function through the AGE-RAGE signaling pathway. All published experimental and clinical studies were included in tables. The AGE-RAGE signaling is involved in diabetic complications such as nephropathy, neuropathy, retinopathy, and osteopathy. Some clinical results in diabetic patients could be potentially attributed to AGE-RAGE signaling consequences. However, the AGE-RAGE signaling pathway has some helpful roles in many tissues, including an increase in osteogenic function. Soluble RAGE (sRAGE), as a ligand decoy, may increase in either condition of RAGE production or destruction, and then it cannot always reflect the AGE-RAGE signaling. Although various medicines are capable to target the AGE-RAGE axis. They can also limit the associated damaging consequences. Recombinant sRAGE can block the AGE-RAGE signaling pathway; however, it is associated with some limitations such as accessibility to AGEs, increase in other RAGE ligands, and a long half-life (24 hours). It is associated with losing the beneficial effect of AGE/RAGE. As a result, sRAGE is not a helpful marker to assess the activity of the RAGE signaling pathway. The recombinant sRAGE cannot be translated into clinical practice due to its limitations.

Sign in / Sign up

Export Citation Format

Share Document