Development of a novel in vitro insulin resistance model in primary human tenocytes for diabetic tendinopathy research

Background Type 2 diabetes mellitus (T2DM) had been reported to be associated with tendinopathy. However, the underlying mechanisms of diabetic tendinopathy still remain largely to be discovered. The purpose of this study was to develop insulin resistance (IR) model on primary human tenocytes (hTeno) culture with tumour necrosis factor-alpha (TNF-α) treatment to study tenocytes homeostasis as an implication for diabetic tendinopathy. Methods hTenowere isolated from human hamstring tendon. Presence of insulin receptor beta (INSR-β) on normal tendon tissues and the hTeno monolayer culture were analyzed by immunofluorescence staining. The presence of Glucose Transporter Type 1 (GLUT1) and Glucose Transporter Type 4 (GLUT4) on the hTeno monolayer culture were also analyzed by immunofluorescence staining. Primary hTeno were treated with 0.008, 0.08, 0.8 and 8.0 µM of TNF-α, with and without insulin supplement. Outcome measures include 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) assay to determine the glucose uptake activity; colourimetric total collagen assay to quantify the total collagen expression levels; COL-I ELISA assay to measure the COL-I expression levels and real-time qPCR to analyze the mRNA gene expressions levels of Scleraxis (SCX), Mohawk (MKX), type I collagen (COL1A1), type III collagen (COL3A1), matrix metalloproteinases (MMP)-9 and MMP-13 in hTeno when treated with TNF-α. Apoptosis assay for hTeno induced with TNF-α was conducted using Annexin-V FITC flow cytometry analysis. Results Immunofluorescence imaging showed the presence of INSR-β on the hTeno in the human Achilles tendon tissues and in the hTeno in monolayer culture. GLUT1 and GLUT4 were both positively expressed in the hTeno. TNF-α significantly reduced the insulin-mediated 2-NBDG uptake in all the tested concentrations, especially at 0.008 µM. Total collagen expression levels and COL-I expression levels in hTeno were also significantly reduced in hTeno treated with 0.008 µM of TNF-α. The SCX, MKX and COL1A1 mRNA expression levels were significantly downregulated in all TNF-α treated hTeno, whereas the COL3A1, MMP-9 and MMP-13 were significantly upregulated in the TNF–α treated cells. TNF-α progressively increased the apoptotic cells at 48 and 72 h. Conclusion At0.008 µM of TNF-α, an IR condition was induced in hTeno, supported with the significant reduction in glucose uptake, as well as significantly reduced total collagen, specifically COL-I expression levels, downregulation of candidate tenogenic markers genes (SCX and MKX), and upregulation of ECM catabolic genes (MMP-9 and MMP-13). Development of novel IR model in hTeno provides an insight on how tendon homeostasis could be affected and can be used as a tool for further discovering the effects on downstream molecular pathways, as the implication for diabetic tendinopathy.

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Alleviative Effect of Ruellia tuberosa L. on Insulin Resistance and Abnormal Lipid Accumulation in TNF-α-Treated FL83B Mouse Hepatocytes

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9967910 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Hong-Jie Chen ◽

Chih-Yuan Ko ◽

Jian-Hua Xu ◽

Yu-Chu Huang ◽

James Swi-Bea Wu ◽

...

Keyword(s):

Insulin Resistance ◽

Ethyl Acetate ◽

Glucose Uptake ◽

Insulin Signaling ◽

Lipid Accumulation ◽

Glucose Transporter ◽

Peroxisome Proliferator ◽

Glucose Transporter 2 ◽

Tnf Α ◽

Mouse Hepatocytes

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and most patients with T2DM develop nonalcoholic fatty liver disease (NAFLD). Both diseases are closely linked to insulin resistance (IR). Our previous studies demonstrated that Ruellia tuberosa L. (RTL) extract significantly enhanced glucose uptake in the skeletal muscles and ameliorated hyperglycemia and IR in T2DM rats. We proposed that RTL might be via enhancing hepatic antioxidant capacity. However, the potent RTL bioactivity remains unidentified. In this study, we investigated the effects of RTL on glucose uptake, IR, and lipid accumulation in vitro to mimic the T2DM accompanied by the NAFLD paradigm. FL83B mouse hepatocytes were treated with tumor necrosis factor-α (TNF-α) to induce IR, coincubated with oleic acid (OA) to induce lipid accumulation, and then, treated with RTL fractions, fractionated with n-hexane or ethyl acetate (EA), from column chromatography, and analyzed by thin-layer chromatography. Our results showed that the ethyl acetate fraction (EAf2) from RTL significantly increased glucose uptake and suppressed lipid accumulation in TNF-α plus OA-treated FL83B cells. Western blot analysis showed that EAf2 from RTL ameliorated IR by upregulating the expression of insulin-signaling-related proteins, including protein kinase B, glucose transporter-2, and peroxisome proliferator-activated receptor alpha in TNF-α plus OA-treated FL83B cells. The results of this study suggest that EAf2 from RTL may improve hepatic glucose uptake and alleviate lipid accumulation by ameliorating and suppressing the hepatic insulin signaling and lipogenesis pathways, respectively, in hepatocytes.

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Extract of white sweet potato tuber against TNF-α-induced insulin resistant by activating the PI3K/Akt pathway in C2C12 myotubes

10.21203/rs.3.rs-97640/v1 ◽

2020 ◽

Author(s):

Chiao-Ming Chen ◽

Viola Varga ◽

Lie-Fen Shyur ◽

Shu-Chi Mu ◽

Sing-Chung Li

Keyword(s):

Insulin Resistance ◽

Ethyl Acetate ◽

Glucose Uptake ◽

Sweet Potato ◽

Glucose Transporter ◽

Akt Pathway ◽

C2c12 Myotubes ◽

C2c12 Myoblast ◽

Insulin Resistant ◽

Tnf Α

Abstract Background White sweet potato (WSP; I. batatas L. Simon No.1) has many potential beneficial effects on metabolic control and diabetes-related insulin resistance. The improvement of insulin resistance by WSP tuber extracts on glucose uptake were not investigated in C2C12 myoblast cells. Results WSP tuberous ethanol extract (WSP-E), partition with ethyl-acetate and water to got ethyl-acetate layer (WSP-EA) and water layer (WSP-EW) have highest total phenol contents and antioxidant activity respectively. After low concentration horse serum on differentiation inducement of C2C12 myoblasts into mature myotubes, treated with TNF-α to induce insulin resistant, WSP-EA and WSP-EW extracts increased the uptake of fluorescence glucose analogue (2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-d-glucose, 2-NBDG) in a dose depend manner by flow cytometry. The WSP-EA enhanced glucose uptake by activation of phosphorylation of IR (pIR), IRS-1 (pIRS-1) and Akt (pAkt) involved in PI3K (phosphatidylinositol 3-kinase) / protein kinase B (Akt) pathway, also upregulated glucose transporter 4 (GLUT4) expression in myotubes. Conclusions WSP-EA enhanced the glucose uptake in C2C12 myotubes through upregulating the PI3K/Akt pathway. WSP tuber extracts has potential applications to improve insulin resistance in diabetes in vitro.

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Statin reverses reduction of adiponectin receptor expression in infarcted heart and in TNF-α-treated cardiomyocytes in association with improved glucose uptake

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00310.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. H3490-H3497 ◽

Cited By ~ 29

Author(s):

Yukio Saito ◽

Daisuke Fujioka ◽

Ken-ichi Kawabata ◽

Tsuyoshi Kobayashi ◽

Toshiaki Yano ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Uptake ◽

Cultured Cells ◽

Myocardial Dysfunction ◽

Statin Treatment ◽

Receptor Expression ◽

Expression Levels ◽

Protein Levels ◽

Tnf Α ◽

Cultured Cardiomyocytes

Statin treatment improves insulin resistance in skeletal muscle. Thus this study assessed whether statin may affect the myocardial expression levels of AdipoR1 and AdipoR2, receptors of adiponectin that enhance insulin sensitivity, and whether statin may improve insulin resistance in cardiomyocytes. Myocardial infarction (MI) was created by the ligation of the left coronary artery in male mice. Expression levels of mRNA and protein levels of AdipoR1 but not of AdipoR2 were significantly decreased in the remote area as well as in the healed infarcted area in the left ventricles 4 wk after MI. Oral administration of pravastatin (50 mg·kg−1·day−1 for 4 wk after MI) reversed the decrease in myocardial expression levels of AdipoR1 independently of changes in serum lipid profiles and insulin levels. With the use of cultured cardiomyocytes, incubation with tumor necrosis factor (TNF)-α, a mediator of postinfarction myocardial dysfunction, inhibited AdipoR1 mRNA and protein expression levels. Coincubation of the cells with pravastatin reversed the inhibitory effects of TNF-α on AdipoR1 expression. In parallel, pravastatin reversed the TNF-α-induced decrease in globular adiponectin-induced 2-deoxy-d-[3H]glucose uptake in insulin-treated cultured cells. Moreover, this effect of pravastatin was inhibited by the suppression of AdipoR1 expression by small-interfering RNA specific for AdipoR1. Incubation with H2O2 reduced AdipoR1 expression in cultured cardiomyocytes that were attenuated by N-acetyl-l-cysteine or pravastatin. Pravastatin suppressed TNF-α-induced intracellular oxidants in cultured cardiomyocytes. In conclusion, pravastatin reversed the reduction of AdipoR1 expression in postinfarction mouse myocardium and in TNF-α-treated cardiomyocytes partly through an antioxidative mechanism in association with improved glucose uptake.

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Hypoglycemic Effect of Vitexin in C57BL/6J Mice and HepG2 Models

Journal of Food Quality ◽

10.1155/2021/5535476 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Weidong Xu ◽

Jiayao Li ◽

Weipeng Qi ◽

Ye Peng

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Blood Glucose ◽

Glucose Uptake ◽

Lipid Content ◽

Hepg2 Cells ◽

Body Weight Gain ◽

Tnf Α ◽

Hepatic Lipid Content

Apigenin-8-C-glucoside (vitexin), a natural phytochemical contained in hawthorn, has been reported to have versatile beneficial bioactivities, such as antioxidation, anticancer property, and adipogenesis inhibition. The present research aimed to determine the influence of vitexin on insulin resistance elicited by HFD in mice and HepG2 cells. Vitexin markedly alleviated body weight gain and improved glucose and insulin intolerance induced by HFD. Vitexin partially normalized blood glucose, cholesterol, TNF-α, and hepatic lipid content. Moreover, vitexin recovered the reduced glucose uptake induced by glucosamine. The present results indicate that vitexin prevents HFD-induced insulin resistance.

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PCB126-mediated effects on adipocyte energy metabolism and adipokine secretion may result in abnormal glucose uptake in muscle cells

10.1101/2020.07.07.192245 ◽

2020 ◽

Author(s):

Audrey Caron ◽

Fozia Ahmed ◽

Vian Peshdary ◽

Léa Garneau ◽

Ella Atlas ◽

...

Keyword(s):

Insulin Resistance ◽

Energy Metabolism ◽

Glucose Uptake ◽

Mitochondrial Function ◽

Muscle Metabolism ◽

Insulin Resistant ◽

Mediated Effects ◽

Tnf Α ◽

Coplanar Polychlorinated Biphenyls ◽

Amp Activated Protein Kinase

AbstractBackgroundExposure to coplanar polychlorinated biphenyls (PCBs) is linked to the development of insulin resistance. Previous studies suggested that PCB126 alters muscle mitochondrial function through an indirect mechanism. Since PCBs are stored in fat, we hypothesized that PCB126 alters adipokine secretion, which in turn affects muscle metabolism.ObjectivesThe objectives of this study were: 1) To study the impacts of PCB126 exposure on adipocyte cytokine/adipokine secretion; 2) To determine whether adipocyte-derived factors alter glucose metabolism and mitochondrial function in myotubes when exposed to PCB126; 3) To determine whether pre-established insulin resistance alters the metabolic responses of adipocytes exposed to PCB126 and the communication between adipocytes and myotubes.Method3T3-L1 adipocytes were exposed to PCB126 (1-100 nM) in two insulin sensitivity conditions (insulin sensitive (IS) and insulin resistant (IR) adipocytes), followed by the measurement of secreted adipokines, mitochondrial function and insulin-stimulated glucose uptake. Communication between adipocytes and myotubes was reproduced by exposing C2C12 or mouse primary myotubes to conditioned medium (CM) derived from IS or IR 3T3-L1 adipocytes exposed to PCB126. Mitochondrial function and insulin-stimulated glucose uptake were then determined in myotubes.ResultsPCB126 significantly increased adipokine (adiponectin, IL-6, MCP-1, TNF-α) secretion and decreased mitochondrial function, glucose uptake and glycolysis in IR but not in IS 3T3-L1 adipocytes. Altered energy metabolism in IR 3T3-L1 adipocytes was linked to decreased phosphorylation of AMP-activated protein kinase (p-AMPK) and increased superoxide dismutase 2 levels, an enzyme involved in reactive oxygen species detoxification. Exposure of myotubes to CM from PCB126-treated IR adipocytes decreased glucose uptake, without altering glycolysis or mitochondrial function. Interestingly, p-AMPK levels were increased rather than decreased in myotubes exposed to the CM of PCB126-treated IR adipocytes.ConclusionTaken together, these data suggest that increased adipokine secretion from IR adipocytes exposed to PCB126 may explain impaired glucose uptake in myotubes.

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The Roles of Liver Inflammation and the Insulin Signaling Pathway in PM2.5 Instillation-Induced Insulin Resistance in Wistar Rats

Disease Markers ◽

10.1155/2021/2821673 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Zhihua Zhang ◽

Shujun Hu ◽

Ping Fan ◽

Ling Li ◽

Shanshan Feng ◽

...

Keyword(s):

Insulin Resistance ◽

Rat Liver ◽

Insulin Signaling ◽

Glucose Transporter ◽

Fasting Blood Glucose ◽

Model Assessment ◽

Glucose Transporter 2 ◽

Systemic Insulin Resistance ◽

Tnf Α ◽

Phosphorylated Akt

To elucidate the mechanism of how the liver participates in PM2.5-caused insulin resistance. A novel Wistar rat model was developed in this study by instilling a suspension of lyophilized PM2.5 sample (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) collected from the atmosphere. Systemic insulin resistance indicators, including serum fasting blood glucose (FBG), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and hemoglobin A1 (HbA1), were upregulated by the PM2.5 instillation. The area under the curve (AUCglu) calculated by intraperitoneal glucose tolerance testing (IPGTT) was also significantly greater in the PM2.5 instillation groups. Additionally, PM2.5 instillation was found to cause liver damage and inflammation. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly elevated by PM2.5 instillation. PM2.5 also triggered IL-6 and TNF-α transcription but inhibited mRNA synthesis and suppressed signaling activation of the insulin-phosphoinositide 3-kinase- (PI3K-) Akt-glucose transporter 2 (GLUT2) pathway in the rat liver by reducing the ratio of phosphorylated Akt to phosphorylated insulin receptor substrate 1 (IRS-1). Thus, PM2.5-induced inflammation activation and insulin signaling inhibition in the rat liver contribute to the development of systemic insulin resistance.

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5220Maternal high-fat diet exaggerates the development of diet-induced insulin resistance in adult offspring by enhancing pyroptosis through augmented gasdermin D-mediated pore formation

European Heart Journal ◽

10.1093/eurheartj/ehz746.0069 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

N Wada ◽

H Yamada ◽

S Motoyama ◽

M Saburi ◽

T Sugimoto ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Pore Formation ◽

Flow Cytometric Analysis ◽

Adult Offspring ◽

High Fat ◽

Expression Levels ◽

Caspase 1 ◽

Flow Cytometric ◽

Tnf Α

Abstract Background Maternal high-fat diet (HFD) has been shown to promote the development of insulin resistance (IR) in adult offspring; however, the underlying mechanisms remain unclear. Approach and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating, and received during pregnancy and lactation. Eight-week-old male offspring of both groups were fed a HFD for 8 weeks. Offspring of HFD-fed dams (O-HFD) showed significantly enhanced IR compared with offspring of ND-fed dams (O-ND). There was no difference in body weight, epidydimal white adipose tissue (eWAT) weight, and cumulative caloric intake between the 2 groups. However, eWAT adipocyte size was significantly increased in O-HFD, accompanied by the abundant crown-like structures. Flow cytometric analysis revealed an increased percentage of M1, but not M2, macrophages. Serum and eWAT concentrations of IL-1β, but not TNF-α, were significantly higher in O-HFD than O-ND (3.7-fold and 2.0-fold, respectively, P<0.05). Treatment with NLRP3 inflammasome inhibitor MCC950 completely abrogated the enhanced IR in O-HFD to a similar extent of that in O-ND, although IR was modestly, but not significantly, ameliorated in O-ND even after MCC950 treatment. Consistent with in vivo findings, in vitro polarization of bone marrow-derived macrophages (BMDMs) did not show any difference in TNF-α mRNA expression after conventional stimulation. In contrast, palmitate acid (PA)-mediated metabolic activation of BMDMs following LPS priming showed a significantly higher concentration of IL-1β in culture supernatants from O-HFD (45%, P<0.05). However, protein expression levels of NLRP-3, ASC, and procaspase-1 after LPS priming were equivalent between the 2 groups. Consistently, intracellular flow cytometric analysis of caspase-1 activity after PA activation did not show any difference, which was compatible with the finding that ex vivo caspase-1 activity of eWAT assessed by fluorescent image of IVIS revealed no difference between the 2 groups. To further examine the mechanism of augmented IL-1β release in BMDM of O-HFD, we examined the cleavage of caspase substrate gasdermin D (GSDMD) and subsequent pore formation. Protein and gene expression levels of GSDM-D after LPS priming were significantly higher in O-HFD (50% and 381%, respectively, P<0.05). At 2 hrs after PA stimulation following LPS priming, cleaved GSDM-D was significantly increased in O-HFD (80%, P<0.01). Consistently, percentage of pore formation assessed by ethidium bromide staining was significantly higher in O-HFD (60%, P<0.05), while LDH release could not be observed. Conclusions Our findings demonstrate that maternal HFD exaggerates diet-induced insulin resistance in adult offspring by enhancing pyroptosis through augmented GSDM-D-mediated pore formation.

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Glucose-dependent insulinotropic polypeptide induces cytokine expression, lipolysis, and insulin resistance in human adipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00100.2012 ◽

2013 ◽

Vol 304 (1) ◽

pp. E1-E13 ◽

Cited By ~ 43

Author(s):

Katharina Timper ◽

Jean Grisouard ◽

Nadine S. Sauter ◽

Tanja Herzog-Radimerski ◽

Kaethi Dembinski ◽

...

Keyword(s):

Insulin Resistance ◽

Mrna Expression ◽

Glucose Uptake ◽

Glucose Transporter ◽

Hormone Sensitive Lipase ◽

Human Adipocytes ◽

Chemotactic Protein ◽

Fatty Acid Release ◽

Glucose Transporter Glut4

Obesity-related insulin resistance is linked to a chronic state of systemic and adipose tissue-derived inflammation. Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone also acting on adipocytes. We investigated whether GIP affects inflammation, lipolysis, and insulin resistance in human adipocytes. Human subcutaneous preadipocyte-derived adipocytes, differentiated in vitro, were treated with human GIP to analyze mRNA expression and protein secretion of cytokines, glycerol, and free fatty acid release and insulin-induced glucose uptake. GIP induced mRNA expression of IL-6, IL-1β, and the IL-1 receptor antagonist IL-1Ra, whereas TNFα, IL-8, and monocyte chemotactic protein (MCP)-1 remained unchanged. Cytokine induction involved PKA and the NF-κB pathway as well as an autocrine IL-1 effect. Furthermore, GIP potentiated IL-6 and IL-1Ra secretion in the presence of LPS, IL-1β, and TNFα. GIP induced lipolysis via activation of hormone-sensitive lipase and was linked to NF-κB activation. Finally, chronic GIP treatment impaired insulin-induced glucose uptake possibly due to the observed impaired translocation of glucose transporter GLUT4. In conclusion, GIP induces an inflammatory and prolipolytic response via the PKA -NF-κB-IL-1 pathway and impairs insulin sensitivity of glucose uptake in human adipocytes.

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Pulmonary vascular effect of insulin in a rodent model of pulmonary arterial hypertension

Pulmonary Circulation ◽

10.1086/689908 ◽

2017 ◽

Vol 7 (3) ◽

pp. 624-634 ◽

Cited By ~ 11

Author(s):

Aaron W. Trammell ◽

Megha Talati ◽

Thomas R. Blackwell ◽

Niki L. Fortune ◽

Kevin D. Niswender ◽

...

Keyword(s):

Insulin Resistance ◽

Endothelial Cells ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Glucose Uptake ◽

Insulin Signaling ◽

Glucose Transporter ◽

Western Diet ◽

Mutant Mice ◽

Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is associated with metabolic derangements including insulin resistance, although their effects on the cardiopulmonary disease are unclear. We hypothesized that insulin resistance promotes pulmonary hypertension (PH) development and mutations in type 2 bone morphogenetic protein receptor (BMPR2) cause cellular insulin resistance. Using a BMPR2 transgenic murine model of PAH and two models of inducible diabetes mellitus, we explored the impact of hyperglycemia and/or hyperinsulinemia on development and severity of PH. We assessed insulin signaling and insulin-mediated glucose uptake in human endothelial cells with and without mutations in BMPR2. PH developed in control mice fed a Western diet and PH in BMPR2 mutant mice was increased by Western diet. Pulmonary artery pressure correlated strongly with fasting plasma insulin but not glucose. Reactive oxygen species were increased in lungs of insulin-resistant animals. BMPR2 mutation impaired insulin-mediated endothelial glucose uptake via reduced glucose transporter translocation despite intact insulin signaling. Experimental hyperinsulinemia is strongly associated with PH in both control and BMPR2-mutant mice, though to a greater degree in those with BMPR2 mutation. Human pulmonary endothelial cells with BMPR2 mutation have evidence of reduced glucose uptake due to impaired glucose transporter translocation. These experiments support a role for hyperinsulinemia in pulmonary vascular disease.

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MicroRNAs-Mediated Regulation of Skeletal Muscle GLUT4 Expression and Translocation in Insulin Resistance

Journal of Diabetes Research ◽

10.1155/2017/7267910 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 35

Author(s):

João Victor Esteves ◽

Francisco Javier Enguita ◽

Ubiratan Fabres Machado

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Glycemic Control ◽

Glucose Uptake ◽

Glucose Transporter ◽

Regulation Of Gene Expression ◽

Glut4 Translocation ◽

Therapeutic Approaches ◽

Glut4 Expression ◽

Solute Carrier

The solute carrier family 2 facilitated glucose transporter member 4 (GLUT4) plays a key role in the insulin-induced glucose uptake by muscle and adipose tissues. In prediabetes and diabetes, GLUT4 expression/translocation has been detected as reduced, participating in mechanisms that impair glycemic control. Recently, a class of short endogenous noncoding RNAs named microRNAs (miRNAs) has been increasingly described as involved in the posttranscriptional epigenetic regulation of gene expression. The present review focuses on miRNAs potentially involved in the expression of GLUT4 expression, and proteins related to GLUT4 and translocation in skeletal muscle, seeking to correlate them with insulin resistance and diabetes. So far, miR-21a-5p, miR-29a-3p, miR-29c-3p, miR-93-5p, miR-106b-5p, miR-133a-3p, miR-133b-3p, miR-222-3p, and miR-223-3p have been reported to directly and/or indirectly regulate the GLUT4 expression; and their expression is altered under diabetes-related conditions. Besides, some miRNAs that have been linked to the expression of proteins involved in GLUT4 translocation machinery in muscle could also impact glucose uptake. That makes these miRNAs promising targets for preventive and/or therapeutic approaches, which could improve glycemic control, thus deserving future new investigations.

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