scholarly journals The vascular smooth muscle cell: a therapeutic target in Type 2 diabetes?

2013 ◽  
Vol 125 (4) ◽  
pp. 167-182 ◽  
Author(s):  
Karen E. Porter ◽  
Kirsten Riches
Keyword(s):  
Type 2 Diabetes ◽  
Smooth Muscle ◽  
Cardiovascular Risk ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Experimental Studies ◽  
Metabolic Memory ◽  
Diabetic Patients ◽  
Metabolic Disturbances

The rising epidemic of T2DM (Type 2 diabetes mellitus) worldwide is of significant concern. The inherently silent nature of the disease in its early stages precludes early detection; hence cardiovascular disease is often established by the time diabetes is diagnosed. This increased cardiovascular risk leads to significant morbidity and mortality in these individuals. Progressive development of complications as a result of previous exposure to metabolic disturbances appears to leave a long-lasting impression on cells of the vasculature that is not easily reversed and is termed ‘metabolic memory’. SMCs (smooth muscle cells) of blood vessel walls, through their inherent ability to switch between a contractile quiescent phenotype and an active secretory state, maintain vascular homoeostasis in health and development. This plasticity also confers SMCs with the essential capacity to adapt and remodel in pathological states. Emerging clinical and experimental studies propose that SMCs in diabetes may be functionally impaired and thus contribute to the increased incidence of macrovascular complications. Although this idea has general support, the underlying molecular mechanisms are currently unknown and hence are the subject of intense research. The aim of the present review is to explore and evaluate the current literature relating to the problem of vascular disease in T2DM and to discuss the critical role of SMCs in vascular remodelling. Possibilities for therapeutic strategies specifically at the level of T2DM SMCs, including recent novel advances in the areas of microRNAs and epigenetics, will be evaluated. Since restoring glucose control in diabetic patients has limited effect in ameliorating their cardiovascular risk, discovering alternative strategies that restrict or reverse disease progression is vital. Current research in this area will be discussed.

scholarly journals Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Expression Pattern ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Unsupervised Classification ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract Background Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempted to provide a better understanding of abnormalities in this tissue. Methods We have explored the muscle gene expression pattern in healthy and newly diagnosed T2DM individuals using supervised and unsupervised classification along with examining the potential of sub-typing based on the gene expression pattern in patients.Results A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminate between normoglycemic and diabetic groups. A gene set comprises 26 genes identified, which was able to discriminate healthy from diabetic individuals with 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct clusters with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion This study implies that it seems the disease has triggered through different cellular/molecular mechanisms and it has the potential to be sub-typing. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.

scholarly journals Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery study followed by metabolic modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Gene Expression Patterns ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract BackgroundType 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempted to provide a better understanding of abnormalities in this tissue. MethodsThe muscle gene expression patterns in healthy and newly diagnosed T2DM individuals were explored using supervised and unsupervised classification approach. Moreover, the potential of sub-typing T2DM patients based on the gene expression patterns was evaluated.ResultsA machine-learning technique was applied to identify a gene expression pattern that could discriminate between normoglycemic and diabetic groups. A gene set comprises of 26 genes was found that was able to discriminate healthy from diabetic individuals with 94% accuracy. In addition, three distinct clusters of diabetic patients with different dysregulated genes and metabolic pathways were identified. Conclusions This study implies that it seems the disease has triggered through different cellular/molecular mechanisms, and it has the potential to be categorized in different sub-types. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group. Thus, this approach will help to recommend the appropriate treatment for each subtype in the future.

scholarly journals Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery followed by metabolic modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Critical Role ◽  
Unsupervised Classification ◽  
Gene Expression Patterns ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract BackgroundType 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence worldwide. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake and plays a critical role in T2DM. Here, we sought to provide a better understanding of the abnormalities in this tissue. MethodsThe muscle gene expression patterns were explored in healthy and newly diagnosed T2DM individuals using supervised and unsupervised classification approaches. Moreover, the potential of subtyping T2DM patients was evaluated based on the gene expression patterns.ResultsA machine-learning technique was applied to identify a set of genes whose expression patterns could discriminate diabetic subjects from healthy ones. A gene set comprising of 26 genes was found that was able to distinguish healthy from diabetic individuals with 94% accuracy. In addition, three distinct clusters of diabetic patients with different dysregulated genes and metabolic pathways were identified. Conclusions This study indicates that T2DM is triggered by different cellular/molecular mechanisms, and it can be categorized into different subtypes. Subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of the abnormalities in each group and more effective therapeutic approaches in the future.

scholarly journals Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Expression Pattern ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Unsupervised Classification ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract Background: Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempted to provide a better understanding of abnormalities in this tissue. Methods: We have explored the muscle gene expression pattern in healthy and newly diagnosed T2DM individuals using supervised and unsupervised classification along with examining the potential of sub-typing based on the gene expression pattern in patients.Results: A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminate between normoglycemic and diabetic groups. A gene set comprises 26 genes identified, which was able to discriminate healthy from diabetic individuals with 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct clusters with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion :This study implies that it seems the disease has triggered through different cellular/molecular mechanisms and it has the potential to be sub-typing. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.

scholarly journals Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Unsupervised Classification ◽  
Diabetic Patients ◽  
Molecular Heterogeneity ◽  
Muscle Gene Expression

Abstract Background: Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake thus plays a critical role in T2DM. Here, we attempt to provide a better understanding of abnormalities in this tissue. Methods: We have explored the muscle gene expression pattern in healthy and newly-diagnosed T2DM individuals using supervised and unsupervised classification along with the discovery of potential subtypes of type 2 diabetes. Results: A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminates between normoglycemic and diabetic groups. A gene set comprises of 26 genes identified which was able to discriminate healthy from diabetic individuals with the 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct potential subtypes with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion: This study implies that it seems the disease has triggered through different cellular/molecular mechanisms. Therefore, subtyping of T2DM patients in combination with real clinical profiles of patients will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.

scholarly journals Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Expression Pattern ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Unsupervised Classification ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract Background: Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempt to provide a better understanding of abnormalities in this tissue. Methods: We have explored the muscle gene expression pattern in healthy and newly-diagnosed T2DM individuals using supervised and unsupervised classification along with examining the potential of sub-typing based on the gene expression pattern in patients.Results: A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminates between normoglycemic and diabetic groups. A gene set comprises of 26 genes identified which was able to discriminate healthy from diabetic individuals with the 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct clusters with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion : This study implies that it seems the disease has triggered through different cellular/molecular mechanisms and it has the potential to be sub-typing. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.

scholarly journals Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia

2021 ◽  
Vol 22 (2) ◽  
pp. 660
Author(s):  
María Aguilar-Ballester ◽  
Gema Hurtado-Genovés ◽  
Alida Taberner-Cortés ◽  
Andrea Herrero-Cervera ◽  
Sergio Martínez-Hervás ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Leukocyte Adhesion ◽  
Experimental Studies ◽  
Lipid Lowering ◽  
Foam Cell Formation ◽  
Relevant Parameter

Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.

scholarly journals Molecular mechanisms and the vital roles of resistin, TLR 4, and NF-κB in treating type 2 diabetic complications

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Venkataiah Gudise ◽  
Bimalendu Chowdhury
Keyword(s):  
Type 2 Diabetes ◽  
Effective Treatment ◽  
Diabetic Complications ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Rapid Progression ◽  
Main Body

Abstract Background Type 2 diabetes in obese (≥ 25 and ≥ 30 kg/m2) patients is the foremost cause of cardiovascular complications like stroke, osteoarthritis, cancers (endometrial, breast, ovarian, liver, kidney, colon, and prostate), and vascular complications like diabetic neuropathy, diabetic and retinopathy, and diabetic nephropathy. It is recognized as a global burden disorder with high prevalence in middle-income nations which might lead to a double burden on health care professionals. Hence, this review emphasizes on understanding the complexity and vital signaling tracts involved in diabetic complications for effective treatment. Main body Type 2 diabetes in overweight patients induces the creation of specific ROS that further leads to changes in cellular proliferation, hypothalamus, and fringe. The resistin, TLR4, and NF-κB signalings are mainly involved in the progression of central and fringe changes such as insulin resistance and inflammation in diabetic patients. The overexpression of these signals might lead to the rapid progression of diabetic vascular complications induced by the release of proinflammatory cytokines, chemokines, interleukins, and cyclooxygenase-mediated chemicals. Until now, there has been no curative treatment for diabetes. Therefore, to effectively treat complications of type 2 diabetes, the researchers need to concentrate on the molecular mechanisms and important signaling tracts involved. Conclusion In this review, we suggested the molecular mechanism of STZ-HFD induced type 2 diabetes and the vital roles of resistin, TLR4, and NF-κB signalings in central, fringe changes, and development diabetic complications for its effective treatment. Graphical abstract

Glucagon-like peptide-1 (GLP-1) Biological Role in Patients of Type 2 Diabetes and Metabolic Syndrome

2019 ◽  
Vol 56 (2) ◽  
pp. 227
Author(s):  
Mohammedziyad Abu Awad
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Glucagon Secretion ◽  
Diabetic Patients ◽  
Metabolic Disturbances ◽  
Cvd Risk ◽  
First Line Therapy ◽  
Increased Risk ◽  
Glucagon Like Peptide 1

<p style="margin: 0in 0in 10pt; text-align: justify; line-height: 200%;">Type2 diabetes is estimated to affect 380 million people worldwide in 2025. Patients of this disease are at increased risk of cardiovascular diseases (CVD).The CVD risk is greater when diabetic patients have metabolic syndrome. Thus, the management of metabolic syndrome and CVD is crucial for diabetic patient’s life progress. GLP-1 has positive biological influences on glucose metabolism control by inhibiting glucagon secretion, enhancing insulin secretion and protecting the effects of cells. GLP-1 was also found to have other positive influences including weight loss, appetite sensation and food intake. These are important factors in metabolic disturbances control and CVD management. The paper reviewed several studies regarding the GLP-1 positive concerns. In conclusion, the paper supports the modern proposal of GLP-1 RAs as a first line therapy in initially diagnosed type 2 diabetes patients.</p>

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.

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