DNA Methylation of TXNIP Independently Associated with Inflammation and Diabetes Mellitus in Twins

2021 ◽  
pp. 1-8
Author(s):  
Yijin Xiang ◽  
Zeyuan Wang ◽  
Qin Hui ◽  
Marta Gwinn ◽  
Viola Vaccarino ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Disease Risk ◽  
Inflammatory Biomarkers ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Cell Dysfunction ◽  
Chronic Disease Risk ◽  
Diabetes Development

Abstract Thioredoxin-interacting protein (TXNIP) plays a key role in diabetes development and prognosis through its role in pancreatic β-cell dysfunction and death as well as in upregulating the inflammatory response in hyperglycemia. DNA methylation (DNAm) of TXNIP (TXNIP-cg19693031) is associated with the prevalence and incidence of type 2 diabetes (T2D); however, its role in inflammation and its relationship with T2D remain unclear. We aimed to investigate the epigenetic associations of TXNIP-cg19693031 with a panel of inflammatory biomarkers and to examine whether these inflammatory biomarkers modify the association between TXNIP-cg19693031 methylation and diabetes in 218 middle-aged male twins from the Emory Twin Study. We confirmed the association of TXNIP-cg19693031 DNAm with T2D, as well as with HbA1c, insulin and fasting glucose. We found that hypomethylation at TXNIP-cg19693031 is strongly associated with both type 2 diabetes and higher levels of inflammatory biomarkers (VCAM-1, ICAM-1, MMP-2, sRAGE and P-selectin); however, the relationship between TXNIP-cg19693031 and T2D is independent of the levels of these inflammatory biomarkers. Our results suggest that DNA methylation of TXNIP is linked with multiple biological processes, through which the TXNIP may have broad influence on chronic disease risk.

GGPPS-mediated Rab27A geranylgeranylation regulates β cell dysfunction during type 2 diabetes development by affecting insulin granule docked pool formation

2015 ◽  
Vol 238 (1) ◽  
pp. 109-119 ◽  
Author(s):  
Shan Jiang ◽  
Di Shen ◽  
Wen-Jun Jia ◽  
Xiao Han ◽  
Ning Shen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Diabetes Development ◽  
Insulin Granule ◽  
Pool Formation

scholarly journals Association between the urban environment and chronic disease to identify communities at risk

2019 ◽  
Author(s):  
Ken Wei Tan ◽  
Qianyu Yang ◽  
Yin Ai Lean ◽  
Joel Ruihan Koo ◽  
Alex R Cook ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Acute Myocardial Infarction ◽  
Body Mass Index ◽  
Chronic Disease ◽  
Body Mass ◽  
Disease Risk ◽  
Chronic Disease Risk

Abstract Background: With increasing urbanisation rates, assessments must be made on the impact of the built environment on the health of populations. As the bulk of healthcare expenditure in developed countries is borne by the elderly through chronic disease management and treatment costs, intervening using the built environment can have lasting population-wide effects. Methods: Using two cohort studies for training and validation, we quantified each individual’s local context based on their residential address and derived geographical exposures adapted from the International Physical Activity and the Environment Network guidelines. Bayesian inference was used to develop a regression model that examines the impacts of the geographical exposures and predicts mean body mass index and prevalence of type 2 diabetes mellitus, acute myocardial infarction and stroke by communities. Results: The distance to the nearest retail outlet was found to be negatively associated with body mass index. Our prediction model shows good accuracy (AUC > 0.75) for predicting type 2 diabetes mellitus, acute myocardial infarction and stroke. National-level maps were generated that predict the health of communities by mean body mass index and overall chronic disease risk. Conclusions: The predictive model has the ability to predict on a macro scale the overall health of a community. Understanding the geospatial distribution of chronic disease risk allows for evidence-based policymaking with urban–specific interventions that improve overall population health.

scholarly journals Minireview: Thioredoxin-Interacting Protein: Regulation and Function in the Pancreatic β-Cell

2014 ◽  
Vol 28 (8) ◽  
pp. 1211-1220 ◽  
Author(s):  
Anath Shalev
Keyword(s):  
Type 2 Diabetes ◽  
Cell Biology ◽  
Pancreatic Β Cell ◽  
Insulin Production ◽  
Β Cell ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
And Function

Pancreatic β-cells are responsible for insulin production, and loss of functional β-cell mass is now recognized as a critical step in the pathogenesis of both type 1 and type 2 diabetes. However, the factors controlling the life and death of the pancreatic β-cell have only started to be elucidated. Discovered as the top glucose-induced gene in a human islet microarray study 12 years ago, thioredoxin-interacting protein (TXNIP) has now emerged as such a key player in pancreatic β-cell biology. Since then, β-cell expression of TXNIP has been found to be tightly regulated by multiple factors and to be dramatically increased in diabetic islets. Elevated TXNIP levels induce β-cell apoptosis, whereas TXNIP deficiency protects against type 1 and type 2 diabetes by promoting β-cell survival. TXNIP interacts with and inhibits thioredoxin and thereby controls the cellular redox state, but it also belongs to the α-arrestin family of proteins and regulates a variety of metabolic processes. Most recently, TXNIP has been discovered to control β-cell microRNA expression, β-cell function, and insulin production. In this review, the current state of knowledge regarding regulation and function of TXNIP in the pancreatic β-cell and the implications for drug development are discussed.

scholarly journals Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges

2019 ◽  
Vol 20 (12) ◽  
pp. 2983 ◽  
Author(s):  
Luca Parrillo ◽  
Rosa Spinelli ◽  
Antonella Nicolò ◽  
Michele Longo ◽  
Paola Mirra ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Disease Risk ◽  
Dynamic Nature ◽  
Nutritional Factors ◽  
Targeted Interventions ◽  
Metabolic Disease Risk ◽  
Drug Interventions ◽  
Diabetes And Obesity

A healthy diet improves life expectancy and helps to prevent common chronic diseases such as type 2 diabetes (T2D) and obesity. The mechanisms driving these effects are not fully understood, but are likely to involve epigenetics. Epigenetic mechanisms control gene expression, maintaining the DNA sequence, and therefore the full genomic information inherited from our parents, unchanged. An interesting feature of epigenetic changes lies in their dynamic nature and reversibility. Accordingly, they are susceptible to correction through targeted interventions. Here we will review the evidence supporting a role for nutritional factors in mediating metabolic disease risk through DNA methylation changes. Special emphasis will be placed on the potential of using DNA methylation traits as biomarkers to predict risk of obesity and T2D as well as on their response to dietary and pharmacological (epi-drug) interventions.

Dietary intervention modulates the expression of the splicing machinery in patients at high-risk of type 2 diabetes development: clinical implications

2018 ◽  
Author(s):  
Rio-Moreno Mercedes del ◽  
Emilia Alors-Perez ◽  
Antonio Camargo ◽  
Javier Delgado-Lista ◽  
Juan L. Lopez-Canovas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Risk ◽  
Dietary Intervention ◽  
Clinical Implications ◽  
Diabetes Development ◽  
Splicing Machinery

98-OR: Placental DNA Methylation Changes Associated with Birthweight and Overlaps with Adult Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 98-OR
Author(s):  
FASIL TEKOLA-AYELE ◽  
TSEGASELASSIE WORKALEMAHU ◽  
XUEHUO ZENG
Keyword(s):  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Adult Type
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