MicroRNAs and Oxidative Stress: An Intriguing Crosstalk to Be Exploited in the Management of Type 2 Diabetes

Abstract

Type 2 diabetes is a chronic disease widespread throughout the world, with significant human, social, and economic costs. Its multifactorial etiology leads to persistent hyperglycemia, impaired carbohydrate and fat metabolism, chronic inflammation, and defects in insulin secretion or insulin action, or both. Emerging evidence reveals that oxidative stress has a critical role in the development of type 2 diabetes. Overproduction of reactive oxygen species can promote an imbalance between the production and neutralization of antioxidant defence systems, thus favoring lipid accumulation, cellular stress, and the activation of cytosolic signaling pathways, and inducing β-cell dysfunction, insulin resistance, and tissue inflammation. Over the last few years, microRNAs (miRNAs) have attracted growing attention as important mediators of diverse aspects of oxidative stress. These small endogenous non-coding RNAs of 19–24 nucleotides act as negative regulators of gene expression, including the modulation of redox signaling pathways. The present review aims to provide an overview of the current knowledge concerning the molecular crosstalk that takes place between oxidative stress and microRNAs in the physiopathology of type 2 diabetes, with a special emphasis on its potential as a therapeutic target.

Genetic and Pharmacological Inhibition of GCN2 Ameliorates Hyperglycemia and Insulin Resistance in Type 2 Diabetic Mice

“…Growing evidence suggests that hyperglycemia in T2D can enhance the production of reactive oxygen species (ROS), which leads to excessive oxidative stress [ 33 ]. On the other hand, oxidative stress plays a vital role in the development and pathogenesis of T2DM [ 34 ].…”

Micro-ribonucleic acid modulation with oxidative stress and inflammation in patients with type 2 diabetes mellitus – a review article

“…It is already proven that some miRNAs could influence oxidative stress through the modulation of gene expression of antioxidant enzymes, for example SOD [ 80 ]. Since altered regulation of miRNA is associated with oxidative stress, the miRNA expression restoration to normal values may lead to a new therapeutic approach to prevent oxidative damage [ 83 ]. LaPierre et al documented the influence of miRNAs on b-cell function in different metabolic conditions [ 84 ].…”

“…Regarding T2D, it is interesting to pay attention to the miRNA-200 family, which is important for redox regulation and could be positively modulated by hydrogen peroxide (H 2 O 2 ). Hyperglycemia leads to oxidant protein modification and formation of advanced glycation end products (AGE), which could be modified by different miRNAs [ 83 ]. MitomiRs are recently discovered miRNAs situated in mitochondria and are able to regulate mitochondrial function connected with fatty acid oxidation, which is also linked to oxidative stress [ 83 ].…”

“…Hyperglycemia leads to oxidant protein modification and formation of advanced glycation end products (AGE), which could be modified by different miRNAs [ 83 ]. MitomiRs are recently discovered miRNAs situated in mitochondria and are able to regulate mitochondrial function connected with fatty acid oxidation, which is also linked to oxidative stress [ 83 ]. Sun et al observed redox status improvement by fruit juice ( Actinidia chinensis Planch.)…”

Pathomechanisms of non-coding RNAs and hub genes related to the oxidative stress in diabetic complications

“…1 Growing evidence indicates that T2D could be a severe metabolic condition affecting more than 400 million individuals globally, and predicts that this number might surpass 600 million by 2040. 2,3 Statistical evidence has demonstrated that T2D is a top 10 cause of death globally, killing over 1.5 million people worldwide. 4 Moreover, T2D is the third most significant risk factor for worldwide premature mortality due to inflammation, hyperglycemia, and oxidative stress.…”