scholarly journals Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus

2022 ◽  
Vol 12 ◽  
Author(s):  
Yang Yang ◽  
Ying Luan ◽  
Qi Feng ◽  
Xing Chen ◽  
Bo Qin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Histone Methylation ◽  
High Morbidity ◽  
Global Public Health ◽  
Cellular Processes ◽  
Genetic And Environmental Factors ◽  
Related Proteins

Diabetes mellitus is a global public health challenge with high morbidity. Type 2 diabetes mellitus (T2DM) accounts for 90% of the global prevalence of diabetes. T2DM is featured by a combination of defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. However, the pathogenesis of this disease is complicated by genetic and environmental factors, which needs further study. Numerous studies have demonstrated an epigenetic influence on the course of this disease via altering the expression of downstream diabetes-related proteins. Further studies in the field of epigenetics can help to elucidate the mechanisms and identify appropriate treatments. Histone methylation is defined as a common histone mark by adding a methyl group (-CH3) onto a lysine or arginine residue, which can alter the expression of downstream proteins and affect cellular processes. Thus, in tthis study will discuss types and functions of histone methylation and its role in T2DM wilsed. We will review the involvement of histone methyltransferases and histone demethylases in the progression of T2DM and analyze epigenetic-based therapies. We will also discuss the potential application of histone methylation modification as targets for the treatment of T2DM.

scholarly journals Association of KCNQ1rs2237892C ⟶ T Gene with Type 2 Diabetes Mellitus: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Wen-Jia Han ◽  
Jian-Yi Deng ◽  
Hua Jin ◽  
Li-Ping Yin ◽  
Jin-Xia Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gene Polymorphism ◽  
Genetic Model ◽  
Meta Analysis ◽  
High Morbidity ◽  
Genome Wide Association Studies ◽  
Asian Populations

Background. Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM. Objective. To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility. Methods. A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger’s test were used to evaluate the publication bias of the selected included literature. Results. Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P < 0.00001 ), recessive (OR: 0.73; 95% CI: 0.45,1.18; P < 0.00001 ) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations. Conclusion. This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM.

scholarly journals T2DM: Why Epigenetics?

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Delphine Fradin ◽  
Pierre Bougnères
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Environmental Factors ◽  
Early Life ◽  
Time Dependent ◽  
Phenotypic Traits ◽  
To Come ◽  
Genetic And Environmental Factors

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder influenced by interactions between genetic and environmental factors. Epigenetics conveys specific environmental influences into phenotypic traits through a variety of mechanisms that are often installed in early life, then persist in differentiated tissues with the power to modulate the expression of many genes, although undergoing time-dependent alterations. There is still no evidence that epigenetics contributes significantly to the causes or transmission of T2DM from one generation to another, thus, to the current environment-driven epidemics, but it has become so likely, as pointed out in this paper, that one can expect an efflorescence of epigenetic knowledge about T2DM in times to come.

Necrotizing Fasciitis in a Patient with Type 2 Diabetes Mellitus

2006 ◽  
Vol 96 (1) ◽  
pp. 67-72 ◽  
Author(s):  
David M. Kanuck ◽  
Thomas Zgonis ◽  
Gary Peter Jolly
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Necrotizing Fasciitis ◽  
Subcutaneous Fat ◽  
Disease Process ◽  
Treatment Modalities ◽  
Successful Outcome ◽  
High Morbidity

Necrotizing fasciitis is a soft-tissue infection characterized by extensive necrosis of subcutaneous fat, neurovascular structures, and fascia. In general, fascial necrosis precedes muscle and skin involvement, hence its namesake. Initially, this uncommon and rapidly progressive disease process can present as a form of cellulitis or superficial abscess. However, the high morbidity and mortality rates associated with necrotizing fasciitis suggest a more serious, ominous condition. A delay in diagnosis can result in progressive advancement highlighted by widespread infection, multiple-organ involvement, and, ultimately, death. We present a case of limb salvage in a 52-year-old patient with type 2 diabetes mellitus and progressive fascial necrosis. A detailed review of the literature is presented, and current treatment modalities are described. Aggressive surgical debridement, comprehensive medical management of the sepsis and comorbidities, and timely closure of the resultant wound or wounds are essential for a successful outcome. (J Am Podiatr Med Assoc 96(1): 67–72, 2006)

scholarly journals Role of Epigenetics in the Pathogenesis and Management of Type 2 Diabetes Mellitus

2019 ◽  
Vol 6 ◽  
pp. 20-28
Author(s):  
Tajudeen Yahaya
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Environmental Factors ◽  
Epigenetic Modifications ◽  
Insulin Biosynthesis ◽  
Epigenetic Changes ◽  
Genetic And Environmental Factors

The need to reverse the growing incidence and burden of diabetes mellitus (DM) worldwide has led to more studies on the possible causes of the disease. Genetic and environmental factors had long been suspected in the pathogenesis of a form of the disease known as the Type 2 diabetes mellitus (T2DM). However, more recent studies suggest epigenetic changes could also be involved in the onset of the disease. This review highlights the role of epigenetic modifications in the pathogenesis and management of T2DM. Peer reviewed studies on the subject were retrieved from reputable sources over the internet, and the majority of the studies unanimously implicated epigenetic modifications in the pathogenesis of some cases of the disease. DNA methylation, histone modification and microRNAs mediated pathways were observed to be the main mechanisms of epigenetic changes. These mechanisms are triggered by certain environmental factors such as diets, microbial and pollutant exposure, lifestyles, among others, prior to the onset of T2DM. Epigenetic changes can modify the expressions and functions of certain genes involved in insulin biosynthesis and glucose metabolism, leading to hyperglycemia and insulin resistance, which are hallmarks of T2DM. Fortunately, epigenetic changes can be reversed by blocking or activating the modulating enzymes, thus if the epigenetic aetiology of a diabetic condition is identified, it can be used as a therapeutic strategy.

scholarly journals Impact of health education on attitude regarding oral anti-diabetic drug adherence in type 2 diabetes mellitus, Bengaluru

2018 ◽  
Vol 5 (11) ◽  
pp. 4809
Author(s):  
Lakshmi Hulugappa ◽  
Chethana Ramegowda
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Health Education ◽  
Positive Attitude ◽  
Public Health Problem ◽  
High Morbidity ◽  
Drug Adherence ◽  
Training Centre

Background: Diabetes mellitus, especially type 2 diabetes is an emerging global epidemic and public health problem and associated with high morbidity and mortality among patients. Positive attitude is important for the management of drug adherence in diabetes, hence the present study was taken to assess the effectiveness of health education on oral anti-diabetic drug adherence.Methods: A descriptive and interventional study was conducted at urban health training centre of a medical college, Bengaluru from November 2015 to March 2016. A total of 70 type 2 diabetes mellitus patients only on oral anti-diabetic drugs willing to give informed consent were included in the study. A pre-tested semi-structured proforma was administered and information about socio-demographic profile, and impact of health education intervention on attitude was obtained.Results: Most of the subjects were female (80%), in the age group of 35-45 yrs (34%), illiterate (40%), unemployed (67%) with Class IV (78%) socio-economic status according to modified Kuppuswamy Classification 2014. The mean ±SD age was 52.47±11.06 years. Significant improvement in attitude regarding adherence to oral anti-diabetic medication was found in study subjects following health education intervention.Conclusions: The study revealed that health education regarding the importance of drug adherence is needed to build positive attitude in study subjects.

scholarly journals N1-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jingfan Zhang ◽  
Yu Chen ◽  
Cong Liu ◽  
Ling Li ◽  
Ping Li
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Related Proteins

Objective. To explore the effects of N1-methylnicotinamide (MNAM) on insulin resistance and glucose metabolism in obese type 2 diabetes mellitus (T2DM) mice and regulatory mechanisms of the NAD-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box protein O1 (FOXO1) pathway. Methods. Blood glucose and insulin levels were examined in mice. HE and oil red O staining were used to observe the effects of MNAM on liver lipid deposition in ob/ob mice. Real-time PCR and Western blotting were used to detect expression of gluconeogenesis, insulin signaling-related proteins, and SIRT1/FOXO1 pathway-related proteins. L-O2 cells were cultured as a model of insulin resistance, and MNAM and SIRT1 inhibitors were administered in vivo. Residual glucose and insulin signaling-related proteins were detected and the mechanisms associated with the SIRT1/FOXO1 signaling pathway in insulin resistance explored. Results. MNAM can effectively reduce levels of fasting blood glucose and insulin, improve liver morphology, and reduce lipid accumulation in obese type 2 diabetes mellitus mice. MNAM also downregulates the key proteins in the gluconeogenesis pathway in the liver, upregulates Sirt1 expression, and reduces acetylation of the FOXO1 protein. In vitro, MNAM could promote the glucose uptake capacity of L-O2 cells induced by palmitic acid (PA), a saturated fatty acid that induces IR in various scenarios, including hepatocytes, improving insulin resistance. As Sirt1 expression was inhibited, the reduction of hepatocyte gluconeogenesis and the regulation of the insulin signaling pathway by MNAM were reversed. Conclusion. MNAM activates SIRT1 and inhibits acetylation of FOXO1, which in turn regulates insulin sensitivity in type 2 diabetic mice, leading to a reduction of hepatic glucose output and improvement of insulin resistance.

scholarly journals Cytokines and adipokines in db / db mice after sweetener consumption

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Roxana Valdes-Ramos ◽  
Beatriz Elina Martinez-Carrillo ◽  
Laura Elisa Gutierrez-Pliego ◽  
Jorge Alberto Escoto-Herrera ◽  
Talia Mondragon-Velazquez
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Sweet Taste ◽  
Controlled Study ◽  
High Morbidity ◽  
Peripheral Tissues ◽  
Low Carbohydrate Diet ◽  
Tnf Α

AbstractType 2 Diabetes Mellitus is a chronic diseases with very high morbidity and mortality worldwide; associated with obesity and hypertension and representing at least 90% of all cases of diabetes. It is characterized by insulin resistance in peripheral tissues and a deterioration in its secretion by the pancreatic β-cell. The control and treatment of these patients is a low-carbohydrate diet, for which non-nutritive sweeteners such as sucralose and stevia are being used, maintaining the sweet taste. It is known that these sweeteners are harmless, but the results so far are still controversial. To identify alterations in the secretion of cytokines and adipokines in db/db mice with consumption of sweeteners. We conducted a randomized, controlled study, with 24 eight week-old male db/db mice. They were divided into 4 groups: a) Control (CL), b) Sucrose (SUC), c) Sucralose (SUCL) and c) Stevia (ST). The animals were fed a normal diet and water ad libitum. The sweeteners were administered for 8 weeks diluted in purified water at 41.66 mg/mL of Sucrose and 4.16 mg/mL of Sucralose or Stevia. Blood glucose was quantified daily; water consumption with and without sweetener, food, and BMI, were quantified weekly. The concentration of IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, INF-γ, TGF-β and TNF-α, insulin, adiponectin, resistin and peptide-C in plasma were determined by luminometry. Glucose was found increased at the end of 8 weeks in the SUC group, compared to CL. They consumed more food, water with and without sweetener in the SUC group (p < 0.001), compared with the controls. BMI was higher in the SUC group, compared with the ST group (p < 0.019). ST decreased the secretion of IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, INF-γ and TNF-α, adiponectin and insulin (p < 0.001), but it increased TGF-β, without modifications in resistin (p < 0.051). On the other hand, SUC decreased the secretion of IL-4, IL-5, IL-10, IL-12, INF-γ, TNF-α, adiponectin, insulin and C-peptide (p < 0.028), but increased IL-6, IL-17 and resistin (p < 0.001), without modifications in TGF-β. Sucralose is a non-nutritive sweetener that caused an increase in the BMI of db/db mice, this because it increased the consumption of food. It also modified the secretion of adipokines; while Stevia decreased the secretion of pro-inflammatory cytokines such as IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, INF-γ and TNF-α. Our results suggest that sweetener consumption may alter the inflammatory profile and the production of adipokines in subjects with type 2 diabetes mellitus.

scholarly journals The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

2020 ◽  
Vol 11 ◽  
Author(s):  
Ya-yi Jiang ◽  
Jia-cheng Shui ◽  
Bo-xun Zhang ◽  
Jia-wei Chin ◽  
Ren-song Yue
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Public Health Problem ◽  
Therapeutic Effects ◽  
Global Public Health

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a global public health problem. Studies on T2DM prevention and treatment mostly focus on discovering therapeutic drugs. Artemisinin and its derivatives were originally used as antimalarial treatments. In recent years, the roles of artemisinins in T2DM have attracted much attention. Artemisinin treatments not only attenuate insulin resistance and restore islet ß-cell function in T2DM but also have potential therapeutic effects on diabetic complications, including diabetic kidney disease, cognitive impairment, diabetic retinopathy, and diabetic cardiovascular disease. Many in vitro and in vivo experiments have confirmed the therapeutic utility of artemisinin and its derivatives on T2DM, but no article has systematically demonstrated the specific role artemisinin plays in the treatment of T2DM. This review summarizes the potential therapeutic effects and mechanism of artemisinin and its derivatives in T2DM and associated complications, providing a reference for subsequent related research.

scholarly journals Regulatory MicroRNAs in T2DM and Breast Cancer

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 819
Author(s):  
Ilhaam Ayaz Durrani ◽  
Attya Bhatti ◽  
Peter John
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Tumorigenic Potential ◽  
Cancer Types

MicroRNAs orchestrate the tight regulation of numerous cellular processes and the deregulation in their activities has been implicated in many diseases, including diabetes and cancer. There is an increasing amount of epidemiological evidence associating diabetes, particularly type 2 diabetes mellitus, to an elevated risk of various cancer types, including breast cancer. However, little is yet known about the underlying molecular mechanisms and even less about the role miRNAs play in driving the tumorigenic potential of the cell signaling underlying diabetes pathogenesis. This article reviews the role of miRNA in bridging the diabetes–breast cancer association by discussing specific miRNAs that are implicated in diabetes and breast cancer and highlighting the overlap between the disease-specific regulatory miRNA networks to identify a 20-miRNA signature that is common to both diseases. Potential therapeutic targeting of these molecular players may help to alleviate the socioeconomic burden on public health that is imposed by the type 2 diabetes mellitus (T2DM)–breast cancer association.

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