scholarly journals The role of «metabolic memory» mechanisms in the development and progression of vascular complications of diabetes mellitus

10.14341/7674 ◽  
2017 ◽  
Vol 20 (2) ◽  
pp. 126-134
Author(s):  
Alexander Alexandrovich Chernikov ◽  
Anastasia Sergeevna Severina ◽  
Minara Shamhalovna Shamhalova ◽  
Marina Vladimirovna Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Late Complications ◽  
Metabolic Memory ◽  
Delayed Effect ◽  
Glycation End Products ◽  
Point Of No Return ◽  
Insight Into

The study of diabetes mellitus (DM), its complications and related pathologies has been continuously performed for many years; however, despite the substantial work and outstanding achievements in studying the mechanisms of DM development and the success of new medicinal products for controlling glycaemia, the problems associated with the late complications of DM continue to increase. The importance of glycaemic control in the early stages of DM for the development of complications is seen only after a sufficiently long period of observation. Such a delayed effect of primary good or unsatisfactory metabolic control, which shapes the patients clinical fate to a greater extent, is termed metabolic memory. The disorders developed under the influence of hyperglycaemia persist for long periods after the normalisation of carbohydrate metabolism; moreover, the effect of previous hyperglycaemia extends over the next 20 and even 30 years. Current research is focused on the possible mechanisms of metabolic memory development, including oxidative stress, advanced glycation end products and epigenetic mechanisms. This research will provide insight into potential markers for the early development and progression of vascular complications and new therapeutic possibilities for the future. However, determining the probable point of no return is more important, which implies that a point exists; after this point is crossed, the progression of vascular complications associated with DM cannot be prevented or reversed. The results of numerous experimental studies demonstrate that the prerequisite components of metabolic memory can be used as potential markers of the progression of DM complications, and may be potential therapeutic targets.

Role of methylglyoxal adducts in the development of vascular complications in diabetes mellitus

2003 ◽  
Vol 31 (6) ◽  
pp. 1400-1402 ◽  
Author(s):  
M. Bourajjaj ◽  
C.D.A. Stehouwer ◽  
V.W.M. van Hinsbergh ◽  
C.G. Schalkwijk
Keyword(s):  
Diabetes Mellitus ◽  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Advanced Glycation ◽  
Exact Role ◽  
Dicarbonyl Compound ◽  
Diabetic Vascular Complications ◽  
Glycation End Products ◽  
End Products

Various theories have been proposed to explain the hyperglycaemia-induced pathogenesis of vascular complications of diabetes, including detrimental effects of AGEs (advanced glycation end products) on vascular tissues. Increased formation of the very reactive dicarbonyl compound MGO (methylglyoxal), one of the side-products of glycolysis, and MGO-derived AGEs seem to be implicated in the development of diabetic vascular complications. Although the exact role of MGO and MGO adducts in the development of vascular complications is unknown, receptor-mediated activation of vascular cells by the MGO–arginine adduct hydroimidazolone, as well as intracellular modifications of protein by MGO, seem to be involved. The aim of this mini-review is to assess to what extent MGO is related to vascular complications in diabetes.

Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

scholarly journals Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 18
Author(s):  
Laura Toma ◽  
Camelia Sorina Stancu ◽  
Anca Volumnia Sima
Keyword(s):  
Plasma Proteins ◽  
Diabetes Complications ◽  
Vascular Complications ◽  
High Density Lipoproteins ◽  
Diabetic Patients ◽  
Inflammatory Stress ◽  
Glycation End Products ◽  
Molecular Therapies ◽  
Specific Receptors

Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.

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.

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.

Neural Foundations of Variability in Attachment

2017 ◽  
Author(s):  
Allyson J. Bennett ◽  
William D. Hopkins ◽  
Ruth Feldman ◽  
Valeria Gazzola ◽  
Jay Giedd ◽  
...  
Keyword(s):  
Brain Development ◽  
Animal Studies ◽  
Experimental Studies ◽  
Theory Development ◽  
Single Type ◽  
Negative Consequences ◽  
Cultural Contexts ◽  
The Social ◽  
Insight Into

Neuroscience offers insight into processes that support the development of the social brain within the cultural contexts that permit attachment relationships to form. Both human and nonhuman animal studies are critical to inform theory development and hypothesis testing via descriptive and experimental studies. A scientifically valid evolutionary theory is necessary to account for the remarkable diversity of parenting systems across human and many nonhuman animals. This chapter examines the neural foundations of attachment and poses critical questions that relate to the initiation of this relationship: How does attachment interface with brain development? What is the interplay between attachment and brain development (including elements of bidirectionality)? Are there negative consequences associated with variation in attachment, and are they reversible? Rather than conceptualizing attachment in terms of a single type of relationship, or a rigid developmental channel, this chapter proposes that an expanded consideration of variation is necessary to understand the neural foundations of infant-caregiver relationships, and the role of those relationships in developing competence across the life span. This approach will permit identification of common neurobiological elements of attachment as well as the remarkable plasticity and diversity within and across individuals, cultures, and species.

Radical yields in DNA exposed to ionizing radiation: Role of energy and charge transfer

1990 ◽  
Vol 68 (9) ◽  
pp. 962-966 ◽  
Author(s):  
John H. Miller ◽  
Charles E. Swenberg
Keyword(s):  
Charge Transfer ◽  
Ionizing Radiation ◽  
Mechanistic Model ◽  
Experimental Studies ◽  
High Mobility ◽  
Orientation Dependence ◽  
Model Calculations ◽  
Insight Into ◽  
High Linear Energy Transfer

Theoretical and experimental studies of free-radical yields in oriented DNA samples exposed to ionizing radiation with high linear energy transfer at 77 K are discussed. The dependence of radical yields on the orientation of DNA chains relative to the particle flux is being investigated to gain insight into the role of intramolecular energy and charge transfer processes in radical production and decay. Model calculations based on a thermal-spike approximation are presented and their limitations for predicting the orientation dependence of radical yields observed after neutron irradiation (see C. M. Arroyo et al. Int. J. Radiat. Biol. 50, 789 (1986)) are discussed. A more mechanistic model based on the high mobility of excess electrons in hydrated DNA (D. van Lith et al. J. Chem. Soc. Faraday Trans. 1, 82, 2933 (1986)) is outlined.

scholarly journals Effect of the Air-Water Interface on the Conformation of Amyloid Beta

2020 ◽  
Author(s):  
Suman Samantray ◽  
David Cheung
Keyword(s):  
Conformational Change ◽  
Amyloid Beta ◽  
Md Simulation ◽  
Experimental Studies ◽  
Water Interface ◽  
Air Water Interface ◽  
Protein Conformational Change ◽  
Protein Fibrillation ◽  
Insight Into

Using MD simulation the conformation of the fibril forming protein amyloid beta at the air-water interface. It is found that adsorption at the air-water interface induces the formation of aggregation prone alpha-helical conformations, consistent with experimental studies of amyloid beta. Adsorption on the air-water interface also reduces the number of distinct conformations that the protein exhibits. This provides insight into the role of protein conformational change into the enhancement of protein fibrillation at interfaces.

scholarly journals Effect of the Air-Water Interface on the Conformation of Amyloid Beta

2020 ◽  
Author(s):  
Suman Samantray ◽  
David Cheung
Keyword(s):  
Conformational Change ◽  
Amyloid Beta ◽  
Md Simulation ◽  
Experimental Studies ◽  
Water Interface ◽  
Air Water Interface ◽  
Protein Conformational Change ◽  
Protein Fibrillation ◽  
Insight Into

Using MD simulation the conformation of the fibril forming protein amyloid beta at the air-water interface. It is found that adsorption at the air-water interface induces the formation of aggregation prone alpha-helical conformations, consistent with experimental studies of amyloid beta. Adsorption on the air-water interface also reduces the number of distinct conformations that the protein exhibits. This provides insight into the role of protein conformational change into the enhancement of protein fibrillation at interfaces.

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