scholarly journals Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 706
Author(s):  
Aishwarya R. Vaidya ◽  
Nina Wolska ◽  
Dina Vara ◽  
Reiner K. Mailer ◽  
Katrin Schröder ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Cell Damage ◽  
National Health System ◽  
Vascular Damage ◽  
Circulating Cells ◽  
Environmental Causes ◽  
Vascular Oxidative Stress

Diabetes mellitus is the fifth most common cause of death worldwide. Due to its chronic nature, diabetes is a debilitating disease for the patient and a relevant cost for the national health system. Type 2 diabetes mellitus is the most common form of diabetes mellitus (90% of cases) and is characteristically multifactorial, with both genetic and environmental causes. Diabetes patients display a significant increase in the risk of developing cardiovascular disease compared to the rest of the population. This is associated with increased blood clotting, which results in circulatory complications and vascular damage. Platelets are circulating cells within the vascular system that contribute to hemostasis. Their increased tendency to activate and form thrombi has been observed in diabetes mellitus patients (i.e., platelet hyperactivity). The oxidative damage of platelets and the function of pro-oxidant enzymes such as the NADPH oxidases appear central to diabetes-dependent platelet hyperactivity. In addition to platelet hyperactivity, endothelial cell damage and alterations of the coagulation response also participate in the vascular damage associated with diabetes. Here, we present an updated interpretation of the molecular mechanisms underlying vascular damage in diabetes, including current therapeutic options for its control.

scholarly journals The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

2021 ◽  
Vol 22 (2) ◽  
pp. 803
Author(s):  
Giuseppina Emanuela Grieco ◽  
Noemi Brusco ◽  
Giada Licata ◽  
Daniela Fignani ◽  
Caterina Formichi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Β Cell ◽  
Physiological Mechanisms ◽  
Effective Strategies ◽  
Chronic Hyperglycaemia ◽  
Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

scholarly journals Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

Does Neuronal Damage Precede Vascular Damage in Subjects with Type 2 Diabetes Mellitus and Having No Clinical Diabetic Retinopathy?

2012 ◽  
Vol 47 (4) ◽  
pp. 202-207 ◽  
Author(s):  
Aditya Verma ◽  
Rajiv Raman ◽  
K. Vaitheeswaran ◽  
Swakshyar Saumya Pal ◽  
Gella Laxmi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Neuronal Damage ◽  
Vascular Damage

scholarly journals Pathophysiology of Type 2 Diabetes Mellitus

2020 ◽  
Vol 21 (17) ◽  
pp. 6275 ◽  
Author(s):  
Unai Galicia-Garcia ◽  
Asier Benito-Vicente ◽  
Shifa Jebari ◽  
Asier Larrea-Sebal ◽  
Haziq Siddiqi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Release ◽  
Molecular Mechanisms ◽  
Metabolic Memory ◽  
Insulin Metabolism ◽  
Insulin Synthesis

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.

A Pathway and Network Oriented Approach to Enlighten Molecular Mechanisms of Type 2 Diabetes Using Multiple Association Studies

2020 ◽  
Author(s):  
Burcu Bakir-Gungor ◽  
Miray Unlu Yazici ◽  
Gokhan Goy ◽  
Mustafa Temiz
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Protein Interaction ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Oriented Approach

AbstractDiabetes Mellitus (DM) is a group of metabolic disorder that is characterized by pancreatic dysfunction in insulin producing beta cells, glucagon secreting alpha cells, and insulin resistance or insulin in-functionality related hyperglycemia. Type 2 Diabetes Mellitus (T2D), which constitutes 90% of the diabetes cases, is a complex multifactorial disease. In the last decade, genome-wide association studies (GWASs) for type 2 diabetes (T2D) successfully pinpointed the genetic variants (typically single nucleotide polymorphisms, SNPs) that associate with disease risk. However, traditional GWASs focus on the ‘the tip of the iceberg’ SNPs, and the SNPs with mild effects are discarded. In order to diminish the burden of multiple testing in GWAS, researchers attempted to evaluate the collective effects of interesting variants. In this regard, pathway-based analyses of GWAS became popular to discover novel multi-genic functional associations. Still, to reveal the unaccounted 85 to 90% of T2D variation, which lies hidden in GWAS datasets, new post-GWAS strategies need to be developed. In this respect, here we reanalyze three meta-analysis data of GWAS in T2D, using the methodology that we have developed to identify disease-associated pathways by combining nominally significant evidence of genetic association with the known biochemical pathways, protein-protein interaction (PPI) networks, and the functional information of selected SNPs. In this research effort, to enlighten the molecular mechanisms underlying T2D development and progress, we integrated different in-silico approaches that proceed in top-down manner and bottom-up manner, and hence presented a comprehensive analysis at protein subnetwork, pathway, and pathway subnetwork levels. Our network and pathway-oriented approach is based on both the significance level of an affected pathway and its topological relationship with its neighbor pathways. Using the mutual information based on the shared genes, the identified protein subnetworks and the affected pathways of each dataset were compared. While, most of the identified pathways recapitulate the pathophysiology of T2D, our results show that incorporating SNP functional properties, protein-protein interaction networks into GWAS can dissect leading molecular pathways, which cannot be picked up using traditional analyses. We hope to bridge the knowledge gap from sequence to consequence.

scholarly journals The Pathophysiology of Gestational Diabetes Mellitus

2018 ◽  
Vol 19 (11) ◽  
pp. 3342 ◽  
Author(s):  
Jasmine Plows ◽  
Joanna Stanley ◽  
Philip Baker ◽  
Clare Reynolds ◽  
Mark Vickers
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Overweight And Obesity ◽  
Chronic Hyperglycemia ◽  
Increased Risk

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

scholarly journals there any association of metabolic disturbances with joint destruction and pain?

2019 ◽  
Vol 65 (6) ◽  
pp. 441-456
Author(s):  
E.V. Chetina ◽  
G.A. Markova ◽  
E.P. Sharapova
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Joint Destruction ◽  
Metabolic Disturbances ◽  
Atp Production ◽  
Glucose And Lipid Metabolism ◽  
Common Risk Factors

Osteoarthritis and type 2 diabetes mellitus represent two the most common chronic diseases. They possess many shared epidemiologic traits, have common risk factors, and embody heterogeneous multifactorial pathologies, which develop due to interaction of genetic an environmental factors. In addition, these diseases are often occurring in the same patient. In spite of the differences in clinical manifestation both diseases have similar disturbances of cellular metabolism, primarily associated with ATP production and utilization. The review discusses molecular mechanisms determining pathophysiological processes associated with glucose and lipid metabolism as well as the means aiming to alleviate the disturbances of energy metabolism as a new a therapeutic approach.

scholarly journals Peculiarities of hypoglycaemic therapy in acute coronary syndrome in patients with type 2 diabetes mellitus

2021 ◽  
Vol 25 (2) ◽  
pp. 27
Author(s):  
K. Yu. Nikolaev ◽  
K. I. Bondareva ◽  
A. Ya. Kovaleva ◽  
G. I. Lifshic
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Acute Coronary Syndrome ◽  
Conflict Of Interest ◽  
Molecular Mechanisms ◽  
Protective Action ◽  
Coronary Syndrome ◽  
Antihyperglycaemic Drugs

<p>This study assessed the features of the course of acute coronary syndrome in patients with diabetic neuropathy. Additionally, the role of antihyperglycaemic therapy as a cardio protection factor in this syndrome was determined by analysing the available literature data and clinical guidelines. Various antihyperglycaemic drug groups demonstrate possible molecular mechanisms of protection against ischemic cardiomyocytes. Cardiovascular disease treatment for patients with type 2 diabetes mellitus is rapidly developing. However, many aspects, including the exact mechanisms of the cardio protective action of antihyperglycaemic drugs, the presence of an additional positive effect of antihyperglycaemic drugs for patients with other diseases (e.g. kidney disease and chronic heart failure), and possible primary prevention of cardiovascular events in patients with type 2 diabetes, remain unclear.</p><p>Received 11 September 2020. Revised 16 January 2021. Accepted 10 February 2021.</p><p><strong>Funding: </strong>The study did not have sponsorship.</p><p><strong>Conflict of interest: </strong>Authors declare no conflict of interest.</p>

scholarly journals Alzheimer’s Disease and Type 2 Diabetes Mellitus: Molecular Mechanisms and Similarities

2020 ◽  
Author(s):  
Karla Isabel Lira-De León ◽  
Alma Delia Bertadillo-Jilote ◽  
David Gustavo García-Gutiérrez ◽  
Marco Antonio Meraz-Ríos
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Mechanisms
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