Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways

2016 ◽  
Vol 310 (2) ◽  
pp. H153-H173 ◽  
Author(s):  
Rudo F. Mapanga ◽  
M. Faadiel Essop
Keyword(s):  
Oxidative Stress ◽  
Polyol Pathway ◽  
Cardiovascular Complications ◽  
Hexosamine Biosynthetic Pathway ◽  
Kinase C ◽  
Glycation End Products ◽  
Global Health Problem ◽  
Metabolic Cycle ◽  
Damaging Effects

The incidence of cardiovascular complications associated with hyperglycemia is a growing global health problem. This review discusses the link between hyperglycemia and cardiovascular diseases onset, focusing on the role of recently emerging downstream mediators, namely, oxidative stress and glucose metabolic pathway perturbations. The role of hyperglycemia-mediated activation of nonoxidative glucose pathways (NOGPs) [i.e., the polyol pathway, hexosamine biosynthetic pathway, advanced glycation end products (AGEs), and protein kinase C] in this process is extensively reviewed. The proposal is made that there is a unique interplay between NOGPs and a downstream convergence of detrimental effects that especially affect cardiac endothelial cells, thereby contributing to contractile dysfunction. In this process the AGE pathway emerges as a crucial mediator of hyperglycemia-mediated detrimental effects. In addition, a vicious metabolic cycle is established whereby hyperglycemia-induced NOGPs further fuel their own activation by generating even more oxidative stress, thereby exacerbating damaging effects on cardiac function. Thus NOGP inhibition, and particularly that of the AGE pathway, emerges as a novel therapeutic intervention for the treatment of cardiovascular complications such as acute myocardial infarction in the presence hyperglycemia.

scholarly journals Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 3
Author(s):  
Teresa Salvatore ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
Luca Rinaldi ◽  
Alfredo Caturano ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Clinical Evidence ◽  
Polyol Pathway ◽  
Cardiovascular Complications ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Kinase C ◽  
First Choice ◽  
Glycation End Products

Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin’s efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis.

Oxidative stress and aging: Is methylglyoxal the hidden enemy?This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 273-284 ◽  
Author(s):  
Kaushik M. Desai ◽  
Tuanjie Chang ◽  
Hui Wang ◽  
Ali Banigesh ◽  
Arti Dhar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Cellular Tissue ◽  
Cardiovascular Complications ◽  
Whole Body ◽  
Age Related ◽  
Transport Chain ◽  
Glycation End Products ◽  
Health And Disease

Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.

scholarly journals Glutathione “Redox Homeostasis” and Its Relation to Cardiovascular Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Vladan P. Bajic ◽  
Christophe Van Neste ◽  
Milan Obradovic ◽  
Sonja Zafirovic ◽  
Djordje Radak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Redox Homeostasis ◽  
Cardiovascular Complications ◽  
Homeostatic Mechanism ◽  
Redox Mechanism ◽  
Signaling Mechanisms ◽  
Research Findings ◽  
Glutathione Redox

More people die from cardiovascular diseases (CVD) than from any other cause. Cardiovascular complications are thought to arise from enhanced levels of free radicals causing impaired “redox homeostasis,” which represents the interplay between oxidative stress (OS) and reductive stress (RS). In this review, we compile several experimental research findings that show sustained shifts towards OS will alter the homeostatic redox mechanism to cause cardiovascular complications, as well as findings that show a prolonged antioxidant state or RS can similarly lead to such cardiovascular complications. This experimental evidence is specifically focused on the role of glutathione, the most abundant antioxidant in the heart, in a redox homeostatic mechanism that has been shifted towards OS or RS. This may lead to impairment of cellular signaling mechanisms and elevated pools of proteotoxicity associated with cardiac dysfunction.

scholarly journals The role of diabetes in the onset and development of endothelial dysfunction

2020 ◽  
Vol 66 (1) ◽  
pp. 47-55
Author(s):  
Era B. Popyhova ◽  
Tatiana V. Stepanova ◽  
Dar’ya D. Lagutina ◽  
Tatiana S. Kiriiazi ◽  
Alexey N. Ivanov
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Critical Role ◽  
Vascular Complications ◽  
Glycation End Products ◽  
Smooth Muscle Cell Migration ◽  
Basic Functions ◽  
Cell Migration And Proliferation ◽  
Radical Processes

The vascular endothelium performs many functions. It is a key regulator of vascular homeostasis, maintains a balance between vasodilation and vasoconstriction, inhibition and stimulation of smooth muscle cell migration and proliferation, fibrinolysis and thrombosis, and is involved to regulation of platelet adhesion and aggregation. Endothelial dysfunction (ED) plays the critical role in pathogenesis of diabetes mellitus (DM) vascular complications. The purpose of this review was to consider the mechanisms leading to the occurrence of ED in DM. The paper discusses current literature data concerning the role of hyperglycemia, oxidative stress, advanced glycation end products in endothelial alteration. A separate section is devoted to the particularities of the functioning of the antioxidant system and their significance in the development of ED in DM. The analysis of the literature allows to conclude that pathological activation of glucose utilization pathways causes damage of endothelial cells, which is accompanied by disorders of all their basic functions. Metabolic disorders in DM cause a pronounced imbalance of free radical processes and antioxidant defense, accompanied by oxidative stress of endotheliocytes, which contributes to the progression of ED and the development of vascular complications. Many aspects of multicomponent regulatory reactions in the pathogenesis of the development of ED in DM have not been sufficiently studied.

scholarly journals Curcumin attenuates oxidative stress in liver in Type 1 diabetic rats

2017 ◽  
Vol 12 (1) ◽  
pp. 452-459 ◽  
Author(s):  
Zhenglu Xie ◽  
Xinqi Zeng ◽  
Xiaqing Li ◽  
Binbin Wu ◽  
Guozhi Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Curcumin Treatment ◽  
Kinase C ◽  
Diabetic Model ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Plasma Malondialdehyde

AbstractWe investigated the effect of curcumin on liver anti-oxidative stress in the type 1 diabetic rat model induced by streptozotocin (STZ). Experimental diabetic rats were induced by STZ intraperitoneally. All rats were fed for 21 days including three groups of control (NC), diabetic model (DC) and curcumin-treated (Cur, 1.5 g/kg by gavage). The results showed that curcumin-treatment significantly decreased the blood glucose and plasma malondialdehyde levels, but significantly increased the plasma superoxide dismutase, glutathione peroxidase and reduced glutathione levels. Curcumin treatment decreased the activity of aldose reductase, but increased the plasma glucose-6-phosphate dehydrogenase, glucose synthetase and glucose-polymerizing activities. Curcumin treatment significantly decreased the protein of protein kinase C (PKC) and poly ADP ribose polymerase (PARP) expression in the Cur group compared with the DC group. Moreover, the sorbitol dehydrogenase activity was significantly decreased and deterred glucose enters into the polyol pathway leading to an increased NADPH content in the Cur group compared with the DC group. Our data provides evidence that oxidative stress in diabetic rats may be attenuated by curcumin by inhibiting polyol pathway associated with down-regulated expression of PKC and PARP, as evidenced by both an increase the antioxidant enzymes levels and glycogen biosynthesis enzymes activities.

scholarly journals Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Sonia Sifuentes-Franco ◽  
Diego Enrique Padilla-Tejeda ◽  
Sandra Carrillo-Ibarra ◽  
Alejandra Guillermina Miranda-Díaz
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Oxidative Damage ◽  
Primary Source ◽  
Cellular Receptors ◽  
Kinase C ◽  
Glycation End Products ◽  
Endogenous Antioxidants ◽  
Management Alternatives ◽  
Persistent Hyperglycemia

Diabetic nephropathy (DN) is the second most frequent and prevalent complication of diabetes mellitus (DM). The increase in the production of oxidative stress (OS) is induced by the persistent hyperglycemic state capable of producing oxidative damage to the macromolecules (lipids, carbohydrates, proteins, and nucleic acids). OS favors the production of oxidative damage to the histones of the double-chain DNA and affects expression of the DNA repairer enzyme which leads to cell death from apoptosis. The chronic hyperglycemic state unchains an increase in advanced glycation end-products (AGE) that interact through the cellular receptors to favor activation of the transcription factor NF-κB and the protein kinase C (PKC) system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the extracellular matrix (ECM) in DN. The reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications because the production of ROS increases during the persistent hyperglycemia. The primary source of the excessive production of ROS is the mitochondria with the capacity to exceed production of endogenous antioxidants. Due to the fact that the mechanisms involved in the development of DN have not been fully clarified, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN.

Role of peroxisome proliferator–activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus

2018 ◽  
Vol 37 (11) ◽  
pp. 1187-1198 ◽  
Author(s):  
A Tabassum ◽  
T Mahboob
Keyword(s):  
Oxidative Stress ◽  
Renal Damage ◽  
Peroxisome Proliferator ◽  
Advanced Glycation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Glycation End Products ◽  
End Products

The present study focused on the role of peroxisome proliferator–activated receptor-gamma (PPAR-γ) activation on renal oxidative damages, serum visfatin, and advanced glycation end products (AGEs) in high-fat diet (HFD)-induced type 2 diabetes mellitus. Following the institutional animal ethics committee guidelines, Wistar rats were categorized into five groups: group 1: fed on a normal rat diet; group 2: HFD-induced obese rats (HFD for 8 weeks); group 3: HFD-fed rats treated with rosiglitazone (RSG; 3 mg/kg orally for 7 days); group 4: T2DM rats induced by HFD and low dose of streptozotocin (i.p. 35 mg/kg); group 5: T2DM rats treated with RSG (3 mg/kg orally for 7 days). Serum levels of AGEs and visfatin, renal damage, and oxidative stress were analyzed. Results showed that HFD-induced obesity and T2DM caused an elevated blood glucose, serum AGEs, visfatin, insulin, urea, creatinine, and tissue malondialdehyde, whereas a decreased catalase and superoxide dismutase activity were observed. The PPAR-γ activation via agonist restored these changes. Our findings suggest that AGEs and visfatin possess an important role in the progression of renal oxidative stress, which can be reduced by the PPAR-γ agonist that impede deleterious effects of HFD and HFD-induced T2DM on renal damage.

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