The role of microRNAs in the regulation of insulin signaling pathway with respect to metabolic and mitogenic cascades: A review

Ebrahimi, Reyhane; Bahiraee, Alireza; Niazpour, Farshad; Emamgholipour, Solaleh; Meshkani, Reza

doi:10.1002/jcb.29299

Cited by 22 publications

(19 citation statements)

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“… 7–9 miRNA analogs are attractive drug candidates because the simultaneous modulation of many target genes by a single miRNA analog may provide effective therapies for complex diseases such as diabetes, obesity and NAFLD. 10 For instance, several miRNAs have been implicated in the regulation of insulin signaling, 11 mitochondrial functions and obesity. 12 …”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] miRNA analogs are attractive drug candidates because the simultaneous modulation of many target genes by a single miRNA analog may provide effective therapies for complex diseases such as diabetes, obesity and NAFLD. 10 For instance, several miRNAs have been implicated in the regulation of insulin signaling, 11 mitochondrial functions and obesity. 12 In both mouse models and human subjects, the activation of beige adipocytes is associated with several metabolic benefits, such as reduced obesity, diminished lipotoxicity and increased insulin sensitivity.…”

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confidence: 99%

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Metabolic and energetic benefits of microRNA-22 inhibition

Thibonnier¹,

Esau²,

Ghosh

et al. 2020

BMJ Open Diab Res Care

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IntroductionWe previously demonstrated in primary cultures of human subcutaneous adipocytes and in a mouse model of diet-induced obesity that specific microRNA-22-3p antagomirs produce a significant reduction of fat mass and an improvement of several metabolic parameters. These effects are related to the activation of target genes such as KDM3A, KDM6B, PPARA, PPARGC1B and SIRT1 involved in lipid catabolism, thermogenesis, insulin sensitivity and glucose homeostasis.Research design and methodsWe now report a dedicated study exploring over the course of 3 months the metabolic and energetic effects of subcutaneous administration of our first miR-22-3p antagomir drug candidate (APT-110) in adult C57BL/6 male mice. Body composition, various blood parameters and energy expenditure were measured at several timepoints between week 12 and week 27 of age.ResultsWeekly subcutaneous injections of APT-110 for 12 weeks produced a sustained increase of energy expenditure as early as day 11 of treatment, a significant fat mass reduction, but no change of appetite nor physical activity. Insulin sensitivity as well as circulating glucose, cholesterol and leptin were improved. There was a dramatic reduction of liver steatosis after 3 months of active treatment. RNA sequencing revealed an activation of lipid metabolism pathways in a tissue-specific manner.ConclusionsThese original findings suggest that microRNA-22-3p inhibition could lead to a potent treatment of fat accumulation, insulin resistance, and related complex metabolic disorders such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Metabolic and energetic benefits of microRNA-22 inhibition

Thibonnier¹,

Esau²,

Ghosh

et al. 2020

BMJ Open Diab Res Care

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“…MicroRNAs (miRNAs) are small noncoding RNAs, which are considered as key regulators of gene expression at the posttranscriptional level and multiple pathophysiological processes [7,8]. Accumulated studies have strongly suggested miRNAs are essential in regulating pancreatic β cell functions, the release of insulin, and insulin resistance [9].…”

Section: Introductionmentioning

confidence: 99%

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

Wang

Liu

et al. 2019

Mediators of Inflammation

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MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

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“…[ 54 ] reported that reduced levels of miRNA-146a were associated with IR in Type 2 diabetic patients. Some studies have shown that miRNA-146a may reduce insulin resistance by activating JNK and P38 MAPK pathways which can play a major role in insulin signaling pathway [ 60 , 61 ]. However, as we mentioned, more investigations are needed to extract the exact mechanism in this regard.…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA-122, microRNA-126-3p and microRNA-146a are associated with inflammation in patients with pre-diabetes and type 2 diabetes mellitus: A case control study

et al. 2021

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The prevalence of type 2 diabetes mellitus (T2DM) is increasing dramatically worldwide. Dysregulation of microRNA (miRNA) as key regulators of gene expression, has been reported in numerous diseases including diabetes. The aim of this study was to investigate the expression levels of miRNA-122, miRNA-126-3p and miRNA-146a in diabetic and pre-diabetic patients and in healthy individuals, and to determine whether the changes in the level of these miRNAs are reliable biomarkers in diagnosis, prognosis, and pathogenesis of T2DM. Additionally, we examined the relationship between miRNA levels and plasma concentrations of inflammatory factors including tumor necrosis factor alpha (TNF-α) and interleukin 6 (Il-6) as well as insulin resistance. In this case-control study, participants (n = 90) were allocated to three groups (n = 30/group): T2DM, pre-diabetes and healthy individuals as control (males and females, age: 25–65, body mass index: 25–35). Expression of miRNA was determined by real-time polymerase chain reaction (RT-PCR). Furthermore, plasma concentrations of TNF-α, IL-6 and fasting insulin were measured by enzyme-linked immunosorbent assay. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated as an indicator of insulin resistance. MiRNA-122 levels were higher while miRNA-126-3p and miRNA-146a levels were lower in T2DM and pre-diabetic patients compared to control (p<0.05). Furthermore, a positive correlation was found between miRNA-122 expression and TNF-α (r = 0.82), IL-6 (r = 0.83) and insulin resistance (r = 0.8). Conversely, negative correlations were observed between miRNA-126-3p and miRNA-146a levels and TNF-α (r = -0.7 and r = -0.82 respectively), IL-6 (r = -0.65 and r = -0.78 respectively) as well as insulin resistance (r = -0.67 and r = -0.78 respectively) (all p<0.05). Findings of this study suggest the miRNAs can potentially contribute to the pathogenesis of T2DM. Further studies are required to examine the reproducibility of these findings.

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The role of microRNAs in the regulation of insulin signaling pathway with respect to metabolic and mitogenic cascades: A review

Cited by 22 publications

References 174 publications

Metabolic and energetic benefits of microRNA-22 inhibition

Metabolic and energetic benefits of microRNA-22 inhibition

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus

Circulating microRNA-122, microRNA-126-3p and microRNA-146a are associated with inflammation in patients with pre-diabetes and type 2 diabetes mellitus: A case control study

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