Bridging the Gap Between Genetic Associations and Molecular Mechanisms for Type 2 Diabetes

2013 ◽  
Vol 13 (6) ◽  
pp. 778-785 ◽  
Author(s):  
Hui Jin Ng ◽  
Anna L. Gloyn
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Genetic Associations

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

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.

scholarly journals High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 76 ◽  
Author(s):  
Suresh P. Khadke ◽  
Aniket A. Kuvalekar ◽  
Abhay M. Harsulkar ◽  
Nitin Mantri
Keyword(s):  
Type 2 Diabetes ◽  
Transcription Factors ◽  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
High Energy ◽  
Tolerance Test ◽  
Diabetic Control ◽  
Ppar Γ

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκβ, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.

scholarly journals The Transgenerational Transmission of the Paternal Type 2 Diabetes-Induced Subfertility Phenotype

2021 ◽  
Vol 12 ◽  
Author(s):  
Eva Zatecka ◽  
Romana Bohuslavova ◽  
Eliska Valaskova ◽  
Hasmik Margaryan ◽  
Fatima Elzeinova ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Sperm Quality ◽  
Reproductive Age ◽  
Reproductive Outcomes ◽  
Metabolic Characteristics ◽  
Two Generations ◽  
Negative Impacts ◽  
Health Complications

Diabetes is a chronic metabolic disorder characterized by hyperglycemia and associated with many health complications due to the long-term damage and dysfunction of various organs. A consequential complication of diabetes in men is reproductive dysfunction, reduced fertility, and poor reproductive outcomes. However, the molecular mechanisms responsible for diabetic environment-induced sperm damage and overall decreased reproductive outcomes are not fully established. We evaluated the effects of type 2 diabetes exposure on the reproductive system and the reproductive outcomes of males and their male offspring, using a mouse model. We demonstrate that paternal exposure to type 2 diabetes mediates intergenerational and transgenerational effects on the reproductive health of the offspring, especially on sperm quality, and on metabolic characteristics. Given the transgenerational impairment of reproductive and metabolic parameters through two generations, these changes likely take the form of inherited epigenetic marks through the germline. Our results emphasize the importance of improving metabolic health not only in women of reproductive age, but also in potential fathers, in order to reduce the negative impacts of diabetes on subsequent generations.

scholarly journals Effect of Agmatine on Non-Alcoholic Fatty Liver Disease Induced by Type 2 Diabetes in Rats

2021 ◽  
pp. 127-134
Author(s):  
Samar F. Miski ◽  
Mai A. Alim A. Sattar Ahmad ◽  
Ahmed Esmat
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Histopathological Examination ◽  
Fasting Blood Glucose ◽  
Serum Levels ◽  
Current Data ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Alcoholic Fatty Liver

Aim: To determine the potential hepatoprotective effect of Agmatine (AGM) on NAFLD-induced by Type 2 diabetes mellitus (T2DM) in rats. Study design:  Forty male Wistar rats weighing from (200 -250 g) were distributed at random into five groups (8 rats per group): group 1 as control; group 2 as untreated-T2DM; groups 3 & 4 as T2DM cotreated with AGM (40 & 80 mg/kg/d), while group 5 T2DM cotreated with Silymarin (100 mg/kg/d). Place and duration of study: Department of Pharmacology, Faculty of Medicine, king Abdul-Aziz University; between October 2020 and January 2021. Methodology: A rat model of T2DM with NAFLD complication was established by feeding rats with 10% fructose in drinking water and intraperitoneally injecting them with a single low dose of streptozotocin (STZ) (45mg/kg). The fasting blood glucose was detected, serum levels of hepatic biomarkers were all assessed. Moreover, histopathological examination was performed by hematoxylin and eosin (H&E) staining. Results: STZ induced T2DM in rats causes a significant (p<0.05, n=8) rise in serum levels of FBG, ALT, AST, TB, TC, TG, and LDL in comparison with the corresponding control group. Co-treatment with AGM (40 & 80 mg/kg) and silymarin significantly alleviated hyperglycemia and amended hepatic biomarkers that was reflected on improved histopathological changes. Conclusion: The current data suggest that oral AGM co-treatment could have a hepatoprotective effect against T2DM associated with NAFLD in rats. Further investigations are recommended to elucidate molecular mechanisms accountable for the useful effects of AGM on hepatocytes.

Lipid-Induced Insulin Resistance Mechanisms: The Link to Inflammation and Type 2 Diabetes.

2021 ◽  
pp. 1-9
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Laboratory Data ◽  
Phosphatidyl Inositol ◽  
Resistance Mechanisms ◽  
Cellular Mechanisms ◽  
Insulin Resistant

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus [T2DM] onset. It occurs as a result of disturbances in lipid metabolism and increased levels of circulating free fatty acids [FFAs]. FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased fatty acid flux has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes development. FFAs appear to cause this defect in glucose transport by inhibiting insulin –stimulated tyrosine phosphorylation of insulin receptor substrate-1 [IRS-1] and IRS-1 associated phosphatidyl-inositol 3-kinase activity. A number of different metabolic abnormalities may increase intramyocellular or intrahepatic fatty acid metabolites that induce insulin resistance through different cellular mechanisms. The current review point out the link between enhanced FFAs flux and activation of PKC and how it impacts on both the insulin signaling in muscle and liver as shown from our laboratory data and highlighting the involvement of the inflammatory pathways importance. This embarks the importance of measuring the inflammatory biomarkers in clinical settings.

IL-6 as a Surrogate Biomarker: The IL-6 Clinical Value for the Diagnosis of Insulin Resistance and Type 2 Diabetes.

2021 ◽  
pp. 1-13
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Low Grade ◽  
Clinical Value ◽  
Insulin Resistant ◽  
Tnf Α ◽  
Low Grade Inflammation

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus (T2D). It occurs as a result of lipid disorders and increased levels of circulating free fatty acids (FFAs). FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased levels fatty acid has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes. Among the biomarkers that are accompanying low grade inflammation include IL-1β, IL-6 and TNF-α. The current review point out the importance of measuring the inflammatory biomarkers especially focusing on the conductance and measurement for IL-6 as a screening laboratory test and its diagnostic value in clinical practice.

scholarly journals Increased Expressions of Matrix Metalloproteinases (MMPs) in Prostate Cancer Tissues of Men with Type 2 Diabetes

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 507
Author(s):  
Andras Franko ◽  
Lucia Berti ◽  
Jörg Hennenlotter ◽  
Steffen Rausch ◽  
Marcus O. Scharpf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Type 2 Diabetes ◽  
Matrix Metalloproteinases ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Prostate Tissue ◽  
Nuclear Antigen ◽  
Gene Expressions ◽  
Mesenchymal Transition

Type 2 diabetes (T2D) is associated with worse prognosis of prostate cancer (PCa). The molecular mechanisms behind this association are still not fully understood. The aim of this study was to identify key factors, which contribute to the more aggressive PCa phenotype in patients with concurrent T2D. Therefore, we investigated benign and PCa tissue of PCa patients with and without diabetes using real time qPCR. Compared to patients without diabetes, patients with T2D showed a decreased E-cadherin/N-cadherin (CDH1/CDH2) ratio in prostate tissue, indicating a switch of epithelial-mesenchymal transition (EMT), which is a pivotal process in carcinogenesis. In addition, the gene expression levels of matrix metalloproteinases (MMPs) and CC chemokine ligands (CCLs) were higher in prostate samples of T2D patients. Next, prostate adenocarcinoma PC3 cells were treated with increasing glucose concentrations to replicate hyperglycemia in vitro. In these cells, high glucose induced expressions of MMPs and CCLs, which showed significant positive associations with the proliferation marker proliferating cell nuclear antigen (PCNA). These results indicate that in prostate tissue of men with T2D, hyperglycemia may induce EMT, increase MMP and CCL gene expressions, which in turn activate invasion and inflammatory processes accelerating the progression of PCa.

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