scholarly journals tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors

2021 ◽  
Vol 22 (2) ◽  
pp. 496
Author(s):  
Maria Nicol Arroyo ◽  
Jonathan Alex Green ◽  
Miriam Cnop ◽  
Mariana Igoillo-Esteve
Keyword(s):  
Type 2 Diabetes ◽  
Noncoding Rna ◽  
Cell Function ◽  
Β Cell ◽  
Peripheral Tissues ◽  
Rna Molecules ◽  
Metabolic Traits ◽  
Β Cell Function ◽  
Genetic And Environmental Factors

The global rise in type 2 diabetes results from a combination of genetic predisposition with environmental assaults that negatively affect insulin action in peripheral tissues and impair pancreatic β-cell function and survival. Nongenetic heritability of metabolic traits may be an important contributor to the diabetes epidemic. Transfer RNAs (tRNAs) are noncoding RNA molecules that play a crucial role in protein synthesis. tRNAs also have noncanonical functions through which they control a variety of biological processes. Genetic and environmental effects on tRNAs have emerged as novel contributors to the pathogenesis of diabetes. Indeed, altered tRNA aminoacylation, modification, and fragmentation are associated with β-cell failure, obesity, and insulin resistance. Moreover, diet-induced tRNA fragments have been linked with intergenerational inheritance of metabolic traits. Here, we provide a comprehensive review of how perturbations in tRNA biology play a role in the pathogenesis of monogenic and type 2 diabetes.

scholarly journals Long-noncoding RNA NBR2 via targeting miR-19a-3p regulates pancreatic β cell function and provides novel biomarkers for type 2 diabetes mellitus

2021 ◽  
Author(s):  
Lei Wan ◽  
Xinying Song ◽  
Baoqing Zhu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Noncoding Rna ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function ◽  
Novel Biomarkers

IntroductionType 2 diabetes mellitus (T2DM) is a major kind of diabetes mellitus. This study aimed to analyze the regulatory effect of long noncoding RNA NBR2 on pancreatic  cell function and the related mechanisms, and to analyze the clinical significance of abnormal NBR2 expression in patients with T2DM.Material and methodsThe expression levels of NBR2 and microRNA-19a-3p (miR-19a-3p) were measured using quantitative Real-Time PCR. The glucose-stimulated insulin secretion was measured using ELISA kit, and cell proliferation was examined using Cell Counting Kit-8 (CCK-8) assay. A dual-luciferase reporter assay was used to confirm the relationship between NBR2 and miR-19a-3p. The diagnostic values of NBR2, miR-19a-3p and NBR2 combined with miR-19a-3p were assessed by receiver operating characteristic (ROC) curves.ResultsThe insulin secretion and proliferation of INS-1 cells were inhibited by NBR2 overexpression, and were promoted by NBR2 knockdown. MiR-19a-3p, which was inhibited by NBR2 overexpression, directly mediated the regulatory effects of NBR2 on INS-1 cell function. Increased serum NBR2 level and decreased serum miR-19a-3p level were found in T2DM patients, and a negative correlation was found between NBR2 and miR-19a-3p. The fasting plasma glucose of T2DM patients was positively correlated with serum NBR2 and negatively correlated with serum miR-19a-3p. Both serum NBR2 and miR-19a-3p had certain diagnostic accuracy, whereas, the combined detection of the serum NBR2 and miR-19a-3p showed more considerable diagnostic accuracy.ConclusionsOur findings indicated that NBR2/miR-19a-3p axis regulates pancreatic β cell function, while may be novel biomarkers for the diagnosis of T2DM.

scholarly journals Serum Amylase Levels in Relation to Islet β Cell Function in Patients with Early Type 2 Diabetes

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162204 ◽  
Author(s):  
Lei Zhuang ◽  
Jian-bin Su ◽  
Xiu-lin Zhang ◽  
Hai-yan Huang ◽  
Li-hua Zhao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Serum Amylase ◽  
Cell Function ◽  
Early Type ◽  
Β Cell ◽  
Β Cell Function

Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells

2020 ◽  
Author(s):  
Hayat Aljaibeji ◽  
Noha Mousaad Elemam ◽  
Abdul Khader Mohammed ◽  
Hind Hasswan ◽  
Mahammad Al Thahyabat ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Viability ◽  
Cell Function ◽  
Serum Levels ◽  
Insulin Content ◽  
Β Cell ◽  
Control Subjects ◽  
Β Cell Function

Abstract Let7b-5p is a member of the Let-7 miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of Let7b-5p in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of let7b-5p in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of let7b-5p in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of let7b-5p are significantly (p<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of let7b-5p increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of let7b-5p reduced insulin content and secretion. Modulation of the expression levels of let7b-5p did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in let7b-5p transfected cells revealed a marked dysregulation of Insulin, Pancreatic And Duodenal Homeobox 1 (PDX1), glucokinase (GCK), glucose transporter 2 (GLUT2), and INSR. In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.

scholarly journals Imeglimin Amplifies Glucose-Stimulated Insulin Release from Diabetic Islets via a Distinct Mechanism of Action

2020 ◽  
Author(s):  
Sophie Hallakou-Bozec ◽  
Micheline Kergoat ◽  
Pascale Fouqueray ◽  
Sébastien Bolze ◽  
David E. Moller
Keyword(s):  
Type 2 Diabetes ◽  
Mode Of Action ◽  
Cell Function ◽  
Drug Candidate ◽  
Β Cell ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Predominant Component ◽  
Cyclic Adp Ribose ◽  
Β Cell Function

ABSTRACTPancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with type 2 diabetes; however, the mechanism by which it restores β-cell function is unknown. Here, we show that Imeglimin acutely and directly amplifies GSIS in islets isolated from rodents with Type 2 diabetes via a mode of action that is distinct from other known therapeutic approaches. The underlying mechanism involves increases in the cellular nicotinamide adenine dinucleotide (NAD+) pool – potentially via the salvage pathway and induction of nicotinamide phosphoribosyltransferase (NAMPT) along with augmentation of glucose-induced ATP levels. Further, additional results suggest that NAD+ conversion to a second messenger, cyclic ADP ribose (cADPR), via cyclic ADP ribose hydrolase (CD38) is required for Imeglimin’s effects in islets, thus representing a potential link between increased NAD+ and enhanced glucose-induced Ca2+ mobilization which - in turn - is known to drive insulin granule exocytosis. Collectively, these findings implicate a novel mode of action for Imeglimin that explains its ability to effectively restore β-cell function and provides for a new approach to treat patients suffering from Type 2 diabetes.

scholarly journals Lipotoxicity and β-Cell Failure in Type 2 Diabetes: Oxidative Stress Linked to NADPH Oxidase and ER Stress

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3328
Author(s):  
Eloisa Aparecida Vilas-Boas ◽  
Davidson Correa Almeida ◽  
Leticia Prates Roma ◽  
Fernanda Ortis ◽  
Angelo Rafael Carpinelli
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Nadph Oxidase ◽  
Er Stress ◽  
Cell Function ◽  
Caloric Intake ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

A high caloric intake, rich in saturated fats, greatly contributes to the development of obesity, which is the leading risk factor for type 2 diabetes (T2D). A persistent caloric surplus increases plasma levels of fatty acids (FAs), especially saturated ones, which were shown to negatively impact pancreatic β-cell function and survival in a process called lipotoxicity. Lipotoxicity in β-cells activates different stress pathways, culminating in β-cells dysfunction and death. Among all stresses, endoplasmic reticulum (ER) stress and oxidative stress have been shown to be strongly correlated. One main source of oxidative stress in pancreatic β-cells appears to be the reactive oxygen species producer NADPH oxidase (NOX) enzyme, which has a role in the glucose-stimulated insulin secretion and in the β-cell demise during both T1 and T2D. In this review, we focus on the acute and chronic effects of FAs and the lipotoxicity-induced β-cell failure during T2D development, with special emphasis on the oxidative stress induced by NOX, the ER stress, and the crosstalk between NOX and ER stress.

scholarly journals Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Tyg Index ◽  
Β Cell Function

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

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