Potential risks of endoplasmic reticulum stress on vasculopathy in diabetes

Abstract Endoplasmic reticulum (ER) is an essential cellular organelle known for secretory functions, including protein production and maturation. However, recent advances suggest that ER has a significant role in metabolic functions. When the ER homeostasis is altered due to stressful conditions, it generates coping signaling pathways identified as unfolded protein response (UPR). When this stress persists, ER then initiates cell apoptosis, leading to other pathological conditions such as insulin resistance, macro- and microvascular complications associated with diabetes, and diabetes mellitus. These consequential vasculopathy impose a significant burden on the management of diabetes. The ER stress plays a primary role in the development and progression of diabetes through multiple signaling pathways that cause the initiation of insulin resistance, inflammatory cytokines, and enhanced oxidative stress. The mechanism of ER stress shows that the phosphorylation of either IRE-1α or PERK leads to downstream signaling pathways that activate Jun N-terminal Kinase (JNK) causing stimulation of inflammatory cytokines and insulin resistance. In addition, leakage of Ca2+ via the mitochondria-associated membranes (MAMs) into the mitochondria enhances the generation of reactive oxygen species (ROS), leading to oxidative stress and subsequently the ER stress. Indeed, a comprehensive understanding of ER stress mechanisms and the signaling pathways will assist in understanding potential target for novel therapeutic approaches in the management of diabetes and other related diseases. The current article detailed the possible involvement of ER stress in diabetes associated vasculopathy.

• Publication year

  2020

• Venue

  Obesity Medicine

• Publication date

  2020-08-09

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.obmed.2020.100274
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Key milestones in the diabetes research: A comprehensive update

  2020cited by this paper
• Role of protein kinase C in obesity

  2020cited by this paper
• Endoplasmic reticulum stress and development of insulin resistance in adipose, skeletal, liver, and foetoplacental tissue in diabesity.

  2019cited by this paper
• Endoplasmic Reticulum Stress Activates Unfolded Protein Response Signaling and Mediates Inflammation, Obesity, and Cardiac Dysfunction: Therapeutic and Molecular Approach

  2019cited by this paper
• Potential prophylactic effect of chemical chaperones for alleviation of endoplasmic reticulum stress in experimental diabetic cataract

  2019cited by this paper
• Endoplasmic Reticulum Stress: A Critical Molecular Driver of Endothelial Dysfunction and Cardiovascular Disturbances Associated with Diabetes

  2019cited by this paper
• Research Progresses of the Mechanism of Insulin Resistance in Type II Diabetes

  2019cited by this paper
• Crosstalk Between Oxidative Stress and Endoplasmic Reticulum (ER) Stress in Endothelial Dysfunction and Aberrant Angiogenesis Associated With Diabetes: A Focus on the Protective Roles of Heme Oxygenase (HO)-1

  2019cited by this paper
• Factors affecting obesity and its treatment

  2019cited by this paper
• Emerging role of Unfolded Protein Response (UPR) mediated proteotoxic apoptosis in diabetes.

  2019cited by this paper
• Mechanisms of Insulin Action and Insulin Resistance.

  2018cited by this paper
• Endoplasmic Reticulum Stress in Metabolic Disorders

  2018cited by this paper
• Vascular endothelium dysfunction: a conservative target in metabolic disorders

  2018cited by this paper
• Insulin resistance: Review of the underlying molecular mechanisms

  2018cited by this paper
• In utero programming and early detection of cardiovascular disease in the offspring of mothers with obesity.

  2018cited by this paper
• Endothelial dysfunction in diabetes and hypertension: Role of microRNAs and long non‐coding RNAs

  2018cited by this paper
• Emerging Roles of Vascular Endothelium in Metabolic Homeostasis.

  2018cited by this paper
• Endothelial Cell Metabolism in Atherosclerosis

  2018cited by this paper
• Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications

  2018cited by this paper
• Insulin therapy and its consequences for the mother, foetus, and newborn in gestational diabetes mellitus.

  2018cited by this paper
• Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

  2017cited by this paper
• Endoplasmic reticulum stress and the development of endothelial dysfunction.

  2017cited by this paper
• Insulin/adenosine axis linked signalling.

  2017cited by this paper
• Heme oxygenase (HO)‐1 induction prevents Endoplasmic Reticulum stress‐mediated endothelial cell death and impaired angiogenic capacity

  2017cited by this paper
• Insulin Is a Key Modulator of Fetoplacental Endothelium Metabolic Disturbances in Gestational Diabetes Mellitus

  2016cited by this paper
• Endoplasmic Reticulum Stress and Associated ROS

  2016cited by this paper
• Inhibition of endoplasmic reticulum stress improves coronary artery function in type 2 diabetic mice

  2016cited by this paper
• Vascular endothelium - Gatekeeper of vessel health.

  2016cited by this paper
• Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load.

  2016cited by this paper
• Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum?

  2016cited by this paper
• Roles of LOX-1 in microvascular dysfunction.

  2016cited by this paper
• Role of endothelium-dependent hyperpolarisation and prostacyclin in diabetes.

  2015cited by this paper
• Proteostasis control by the unfolded protein response

  2015cited by this paper
• Methylglyoxal, the dark side of glycolysis

  2015cited by this paper
• Endothelial cell metabolism in normal and diseased vasculature.

  2015cited by this paper
• Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium

  2015cited by this paper
• The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

  2015cited by this paper
• Vascular Endothelial Growth Factor and Angiogenesis in the Regulation of Cutaneous Wound Repair

  2014cited by this paper
• Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells

  2014cited by this paper
• Diseases of Medium-Sized and Small Vessels

  2014cited by this paper
• Endoplasmic reticulum stress in insulin resistance and diabetes.

  2014cited by this paper
• Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 1. An overview.

  2014cited by this paper
• A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and Oxidative Stress

  2014cited by this paper
• Acute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exercise

  2013cited by this paper
• Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.

  2013cited by this paper
• Endoplasmic reticulum stress upregulates protein tyrosine phosphatase 1B and impairs glucose uptake in cultured myotubes

  2013cited by this paper
• Induction of endoplasmic reticulum stress impairs insulin-stimulated vasomotor relaxation in rat aortic rings: role of endothelin-1.

  2013cited by this paper
• Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?

  2012cited by this paper
• Endoplasmic Reticulum Stress Is Involved in Cardiac Damage and Vascular Endothelial Dysfunction in Hypertensive Mice

  2012cited by this paper
• IRE1, a double-edged sword in pre-miRNA slicing and cell death.

  2012cited by this paper
• Recoupling the Cardiac Nitric Oxide Synthases: Tetrahydrobiopterin Synthesis and Recycling

  2012cited by this paper
• Reactive Oxygen and Nitrogen Species in Pathogenesis of Vascular Complications of Diabetes

  2012cited by this paper
• Endoplasmic reticulum stress and type 2 diabetes.

  2012cited by this paper
• New insights into ER stress-induced insulin resistance.

  2012cited by this paper
• Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds

  2012cited by this paper
• Nitric oxide signalling in the regulation of cardiovascular and platelet function.

  2011cited by this paper
• eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity.

  2011cited by this paper
• Endothelium‐mediated control of vascular tone: COX‐1 and COX‐2 products

  2011cited by this paper
• Functional in Vitro Analysis of the ERO1 Protein and Protein-disulfide Isomerase Pathway*

  2011cited by this paper
• Inhibition of Insulin Signaling in Endothelial Cells by Protein Kinase C-induced Phosphorylation of p85 Subunit of Phosphatidylinositol 3-Kinase (PI3K)*

  2011cited by this paper
• The Endoplasmic Reticulum Stress-C/EBP Homologous Protein Pathway-Mediated Apoptosis in Macrophages Contributes to the Instability of Atherosclerotic Plaques

  2010cited by this paper
• The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects.

  2009cited by this paper
• Endothelial dysfunction in diabetes: from mechanisms to therapeutic targets.

  2009cited by this paper
• Vascular endothelial function in health and diseases.

  2008cited by this paper
• Effect of Endothelium-Specific Insulin Resistance on Endothelial Function In Vivo

  2008cited by this paper
• Transcriptional Induction of Mammalian ER Quality Control Proteins Is Mediated by Single or Combined Action of ATF6α and XBP1

  2007cited by this paper
• Cholesterol sensing, trafficking, and esterification.

  2006cited by this paper
• Rough sheets and smooth tubules.

  2006cited by this paper
• Endoplasmic reticulum architecture: structures in flux.

  2006cited by this paper
• The unfolded protein response

  2006cited by this paper
• Compromised arterial function in human type 2 diabetic patients.

  2005cited by this paper
• Endothelial dysfunction.

  2004cited by this paper
• Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes

  2004cited by this paper
• Molecular motors

  2003cited by this paper
• Endothelial dysfunction.

  2003cited by this paper
• ET-1 stimulates ERK signaling pathway through sequential activation of PKC and Src in rat myometrial cells.

  2002cited by this paper
• ER-associated degradation in protein quality control and cellular regulation.

  2002cited by this paper
• Effect of Fluid Shear Stress on the Permeability of the Arterial Endothelium

  2002cited by this paper
• Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB.

  2001cited by this paper
• Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

  2001cited by this paper
• Lipid metabolism and vesicle trafficking: more than just greasing the transport machinery.

  2001cited by this paper
• The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response.

  2000cited by this paper
• Similarities in antagonist affinity profiles of muscarinic M3 and M5 cholinoceptors: Pharmacological difficulties associated with identifying a functional M5 receptor

  1999cited by this paper
• Quality control in the secretory pathway.

  1995cited by this paper
• The Spectrum of Vasculopathies in the Differential Diagnosis of Vasculitis

  1994cited by this paper
• Molecular chaperone functions of heat-shock proteins.

  1993cited by this paper
• Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes.

  1991cited by this paper
• A STUDY OF TISSUE CULTURE CELLS BY ELECTRON MICROSCOPY

  1945cited by this paper

• Relevant Serum Endoplasmic Reticulum Stress Biomarkers in Type 2 Diabetes and Its Complications: A Systematic Review and Meta-Analysis

  2024cites this paper
• Inhibition of Endoplasmic Reticulum Stress Improves Acetylcholine-Mediated Relaxation in the Aorta of Type-2 Diabetic Rats

  2022cites this paper
• Potential Roles of Endoplasmic Reticulum Stress and Cellular Proteins Implicated in Diabesity

  2021cites this paper
• Current Status of Endoplasmic Reticulum Stress in Type II Diabetes

  2021cites this paper