Aberrant Expression of Long Non-Coding RNAs in Newly Diagnosed Type 2 Diabetes Indicates Potential Roles in Chronic Inflammation and Insulin Resistance

Wang, Xiaoli; Xu, Chang; Zhang, Peipei; Liu, Fan; Zhou, Ting; Sun, Kan

doi:10.1159/000484388

Cited by 41 publications

(26 citation statements)

References 38 publications

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“…Transcriptional profiling of blood cell samples from patients with T2DM has revealed several dysregulated lncRNAs with potential roles in inflammation and insulin resistance. 173 RNA sequencing of bone marrow macrophages from obese, diabetic db/db mice showed differential expression of several lncRNAs compared to those of control non-diabetic db/+ mice, including increased expression of E330013P06 , a pro-inflammatory lncRNA that enhances the formation of foam cells [G] . 174 Levels of E330013P06 were also higher in macrophages from mice fed a high-fat diet and in monocytes from humans with T2DM than in chow-fed and non-diabetic counterparts, respectively.…”

Section: Rna Modifications In Dkdmentioning

confidence: 99%

Epigenetics and epigenomics in diabetic kidney disease and metabolic memory

2019

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The development and progression of diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellitus, is influenced by both genetic and environmental factors. DKD is an important contributor to the morbidity of patients with diabetes mellitus, indicating a clear need for an improved understanding of disease aetiology to inform the development of more efficacious treatments. DKD is characterized by an accumulation of extracellular matrix, hypertrophy, and fibrosis in kidney glomerular and tubular cells. Increasing evidence shows that genes associated with these features of DKD are regulated not only by classical signalling pathways, but also by epigenetic mechanisms, involving chromatin histone modifications, DNA methylation, and non-coding RNAs. These mechanisms can respond to changes in the environment and importantly, might mediate the persistent long-term expression of DKD-related genes and phenotypes induced by prior glycaemic exposure, despite subsequent glycaemic control, a phenomenon called metabolic memory. Detection of epigenetic events during the early stages of DKD could be valuable for timely diagnosis and prompt treatment to prevent progression to end-stage renal disease. Identification of epigenetic signatures of DKD via epigenome-wide association studies might also inform precision medicine approaches. Here, we highlight the emerging role of epigenetics and epigenomics in DKD, and the translational potential of candidate epigenetic factors and non-coding RNAs as biomarkers and drug targets for DKD.

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Section: Rna Modifications In Dkdmentioning

confidence: 99%

Epigenetics and epigenomics in diabetic kidney disease and metabolic memory

2019

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“…In human ECs, approximately 100 lncRNAs were found upregulated and 186 down-regulated [116] upon exposure to high glucose. Moreover, the aberrant expression of circulating lncRNAs in T2DM patients seems mostly related to processes such as inflammation, immune response, insulin resistance and regulation of insulin secretion [117]. Recently, the lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript 1) has been found increased in ECs exposed to high glucose, suggesting its potential role in upregulating inflammatory mediators underlying micro- and macrovascular complications [118].…”

Section: Epigenetic Changes In T2dm-related Endothelial Dysfunctionmentioning

confidence: 99%

Can Epigenetics of Endothelial Dysfunction Represent the Key to Precision Medicine in Type 2 Diabetes Mellitus?

Coco

Sgarra

Potenza

et al. 2019

IJMS

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In both developing and industrialized Countries, the growing prevalence of Type 2 Diabetes Mellitus (T2DM) and the severity of its related complications make T2DM one of the most challenging metabolic diseases worldwide. The close relationship between genetic and environmental factors suggests that eating habits and unhealthy lifestyles may significantly affect metabolic pathways, resulting in dynamic modifications of chromatin-associated proteins and homeostatic transcriptional responses involved in the progression of T2DM. Epigenetic mechanisms may be implicated in the complex processes linking environmental factors to genetic predisposition to metabolic disturbances, leading to obesity and type 2 diabetes mellitus (T2DM). Endothelial dysfunction represents an earlier marker and an important player in the development of this disease. Dysregulation of the endothelial ability to produce and release vasoactive mediators is recognized as the initial feature of impaired vascular activity under obesity and other insulin resistance conditions and undoubtedly concurs to the accelerated progression of atherosclerotic lesions and overall cardiovascular risk in T2DM patients. This review aims to summarize the most current knowledge regarding the involvement of epigenetic changes associated with endothelial dysfunction in T2DM, in order to identify potential targets that might contribute to pursuing “precision medicine” in the context of diabetic illness.

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“…Type 2 diabetes (T2D) results from the loss of glucose homeostasis due to insulin resistance and/or β-cell dysfunction and involves genetic, environmental, and behavioral components [1-3]. Studies of the pathogenesis of T2D mainly focus on the mechanisms controlling β-cell adaptation and insulin secretion.…”

Section: Introductionmentioning

confidence: 99%

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

Ruan¹,

Lin²,

Ma³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The islet is an important endocrine organ to secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. Long noncoding RNAs (lncRNAs) are involved in a variety of biological functions and play key roles in many diseases, including type 2 diabetes (T2D). The aim of this study was to determine whether lncRNA-p3134 is associated with glucose metabolism and insulin signaling in pancreatic β cells. Methods: LncRNA microarray technology was used to identify the differentially expressed circulating lncRNAs in T2D patients. RT-PCR analyses were performed to determine the expression of lncRNA-p3134 in 30 pairs of diabetic and non-diabetic patients. The correlation of lncRNA-p3134 to clinical data from T2D patients was analyzed. LncRNA-p3134 was overexpressed in Min6 cells and db/db mice by adenovirus-mediated technology. CCK-8, TUNEL, Western blot, glucose-stimulated insulin secretion (GSIS), ELISAs and immunochemistry were performed to determine the effect of lncRNA-p3134 on proliferation, apoptosis and insulin secretion both in vitro and vivo. Results: The circulating level of lncRNA-p3134 was higher in diabetic patients than in non-diabetic controls and was correlated with fasting blood glucose and HOMA-β levels. The lncRNA-p3134 had risen by 4 times in serum exosomes but nearly unchanged in exosome-free samples. The secretion of lncRNA-p3134 was dynamically modulated by glucose in both Min6 cells and isolated mouse islet cells. LncRNA-p3134 positively regulate GSIS through promoting of key regulators (Pdx-1, MafA, GLUT2 and Tcf7l2) in β cells. In addition, the overexpression of lncRNA-p3134 resulted in a decreased apoptosis ratio and partially reversed the glucotoxicity effects on GSIS function in Min6 cells. The restoration of insulin synthesis and secretion the increase of the insulin positive cells areas by upregulation of lncRNA-p3134 in db/db mice confirmed the compensatory role of lncRNA-p3134 to preserve β-cell function. Furthermore, a protective effect of lncRNA-p3134 on GSIS by positive modulation of PI3K/Akt/mTOR signaling was also confirmed. After blocking the PI3K/AKT signals with their specific inhibitor, the effect of overexpressed lncRNA-p3134 on insulin secretion was obviously attenuated. Conclusion: Taken together, the results of this study provide new insights into lncRNA-p3134 regulation in pancreatic β cells and provide a better understanding of novel mechanism of glucose homeostasis.

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Aberrant Expression of Long Non-Coding RNAs in Newly Diagnosed Type 2 Diabetes Indicates Potential Roles in Chronic Inflammation and Insulin Resistance

Cited by 41 publications

References 38 publications

Epigenetics and epigenomics in diabetic kidney disease and metabolic memory

Epigenetics and epigenomics in diabetic kidney disease and metabolic memory

Can Epigenetics of Endothelial Dysfunction Represent the Key to Precision Medicine in Type 2 Diabetes Mellitus?

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

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