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

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

PeerJ ◽

10.7717/peerj.8740 ◽

2020 ◽

Vol 8 ◽

pp. e8740

Author(s):

Hui Yee Tan ◽

Sik Loo Tan ◽

Seow Hui Teo ◽

Margaret M. Roebuck ◽

Simon P. Frostick ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Uptake ◽

Glucose Transporter ◽

Monolayer Culture ◽

Immunofluorescence Staining ◽

Type I ◽

Expression Levels ◽

Collagen Expression ◽

Total Collagen ◽

Tnf Α

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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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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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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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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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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Abstract 1185: Role Of Sphingosine-1-Phosphate (S1P) In Insulin Signaling.

Circulation ◽

10.1161/circ.116.suppl_16.ii_239-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Suzanne M Nicholl ◽

Elisa Roztocil ◽

Mark G Davies

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Glucose Uptake ◽

Insulin Signaling ◽

Receptor Expression ◽

Serine Phosphorylation ◽

Glucose Disposal ◽

Sphingosine 1 Phosphate ◽

Low Glucose

A failure to increase glucose disposal into peripheral tissues in response to insulin leads to impaired insulin signaling and an inability to uptake glucose leading to the onset of insulin resistance, a major contributing factor to diabetes. We examined the role of sphingosine-1-phosphate (S1P) in insulin signaling and its ability to regulate glucose uptake in skeletal muscle cells. S1P, a sphingolipid found in abundance in the circulation, has been implicated in not only mediating crosstalk with other signaling pathways but has also been implicated in insulin resistance. We hypothesize that S1P interacts with post-receptor insulin signaling to increase glucose disposal in an in vitro model of insulin resistance using differentiated mouse skeletal C2C12 myotubes. Our data demonstrates that S1P (10μM) increases basal glucose levels similar to that observed in response to insulin (100nM) under conditions of low glucose (** p < 0.005: n = 3). Conversely, high glucose conditions completely inhibit both insulin and S1P stimulated glucose uptake (*p < 0.01:n = 3). Pre-incubation with S1P does not augment insulin-induced glucose uptake (***p < 0.001:n = 3), suggesting that S1P does not act via a separate signaling pathway. This is confirmed by our data demonstrating that S1P-induced glucose uptake is abrogated by Cytochalasin B (*p < 0.001:n = 3). In addition, the PI3-K inhibitors, LY294002 and Wortmannin, the Akt inhibitor, AKT2 and the p38MAPK inhibitor, SB203580 significantly inhibited glucose uptake in response to S1P, demonstrating their importance in S1P-induced glucose uptake (*p < 0.05:n = 3). S1P2 and S1P3 receptor expression were upregulated in response to insulin (~2-fold over basal) under low glucose conditions suggesting that insulin may regulate S1P signaling via one or both of these receptors. S1P increased serine phosphorylation of IRS1, both at serine 307 and serines 636/639 maximally after 15 minutes of stimulation. This data has important clinical implications in patients with metabolic syndrome who have impaired skeletal muscle glucose disposal due to insulin resistance and will help guide present and future therapy for patients who have this rapidly growing disease.

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Is there a link between TNF gene expression and cognitive deficits in depression?

Acta Biochimica Polonica ◽

10.18388/abp.2016_1276 ◽

1970 ◽

Vol 64 (1) ◽

Cited By ~ 9

Author(s):

Kinga Bobińska ◽

Elżbieta Gałecka ◽

Janusz Szemraj ◽

Piotr Gałecki ◽

Monika Talarowska

Keyword(s):

Gene Expression ◽

Verbal Memory ◽

Verbal Fluency ◽

Depressive Disorders ◽

Verbal Learning ◽

Test Group ◽

Entire Group ◽

Expression Levels ◽

Protein Levels ◽

Tnf Α

Neuroinflammation is a known factor in the pathogenesis of recurrent depressive disorders. Depression is accompanied by activated immune-inflammatory pathways including increased levels of TNFα, sTNFR1and sTNFR2.The purpose of this study was to analyse the TNF-α, TNFRSF1A and TNFRSF1B genes on both mRNA and protein levels in patients with rDD, and to investigate the relationship between TNF-α,TNFRSF1A and TNFRSF1B gene expression and cognitive performance. The study comprised 158 subjects: patients with recurrent depressive disorder (n=89) and healthy subjects (n=69). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Both mRNA and protein expression levels of all genes were significantly higher in rDD subjects when compared to healthy controls. No statistically significant correlations were observed between the analysed variables in both the rDD group and the HS test group. The only exception was noticed in the HS test group, where increased expression of TNFRSF1A and TNFRSF1B gene negatively affected the performance of the AVLT test. However, statistically significant correlations between TNF, TNFRSF1A, TNFRSF1B mRNA gene expression levels and all the neuropsychological tests used in the survey for the entire group were observed. 1.The results of our study show increased expression of the TNF, TNFRSF1A and TNFRSF1B genes on both mRNA and protein levels in depression. 2. Elevated expression of TNF-α, TNFRSF1A and TNFRSF1B negatively correlates with cognitive efficiency: working memory, executive functions, attention, auditory-verbal memory, effectiveness of learning processes and verbal fluency.

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TNF-α acutely inhibits vascular effects of physiological but not high insulin or contraction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00119.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. E654-E660 ◽

Cited By ~ 40

Author(s):

Lei Zhang ◽

Catherine M. Wheatley ◽

Stephen M. Richards ◽

Eugene J. Barrett ◽

Michael G. Clark ◽

...

Keyword(s):

Insulin Resistance ◽

Muscle Contraction ◽

Glucose Uptake ◽

Capillary Flow ◽

Insulin Dose ◽

Whole Body ◽

Vascular Effects ◽

Capillary Recruitment ◽

Tnf Α

TNF-α is elevated in many states of insulin resistance, and acutely administered TNF-α in vivo inhibits insulin-mediated hemodynamic effects and glucose uptake in muscle. In this study, we assess whether the inhibitory effects of TNF-α are affected by insulin dose or muscle contraction. Whole body glucose infusion rate (GIR), femoral blood flow (FBF), hindleg vascular resistance, hindleg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R′g) and hindleg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, were determined. Three groups were studied with and without infusion of TNF-α: euglycemic insulin-clamped, one-leg field-stimulated (2 Hz, 0.1 ms at 30 V), and saline-infused control anesthetized rats. Insulin infusions were 3, 10, or 30 mU · kg-1 · min-1 for 2 h. 1-MX metabolism was maximally increased by all three doses of insulin. GIR, HGU, and R′g were maximal at 10 mU and FBF was maximal at 30 mU of insulin. Contraction increased FBF, HGU, and 1-MX. TNF-α (0.5 μg · kg-1 · h-1) totally blocked the 3 and 10 mU insulin-mediated increases in FBF and 1-MX, and partly blocked GIR, HGU, and R′g. None of the increases due to twitch contraction was affected by TNF-α, and only the increase in FBF due to 30 mU of insulin was partly affected. We conclude that muscle capillary recruitment and glucose uptake due to high levels of insulin or muscle contraction under twitch stimuli at 2 Hz are resistant to TNF-α. These findings may have implications for ameliorating muscle insulin resistance resulting from increased plasma TNF-α and for the differing mechanisms by which contraction and insulin recruit capillary flow in muscle.

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Leukocyte antigen-related inhibition attenuates palmitate-induced insulin resistance in muscle cells

Journal of Endocrinology ◽

10.1530/joe-12-0160 ◽

2012 ◽

Vol 215 (1) ◽

pp. 71-77 ◽

Cited By ~ 9

Author(s):

Sattar Gorgani-Firuzjaee ◽

Salar Bakhtiyari ◽

Abolfazl Golestani ◽

Reza Meshkani

Keyword(s):

Insulin Resistance ◽

Glucose Uptake ◽

Cell Line ◽

C2c12 Cell ◽

Muscle Cells ◽

C2c12 Cells ◽

Stable Cell Line ◽

Protein Levels ◽

Induce Insulin Resistance ◽

And Control

Palmitate has been shown to induce insulin resistance in skeletal muscle cells. The aim of this study was to investigate the role of the leukocyte common antigen-related (LAR) gene in palmitate-induced insulin resistance in C2C12 cells. A stable C2C12 cell line was generated using LAR short hairpin RNA. The levels of LAR protein and phosphorylation of insulin receptor substrate-1 (IRS1) and Akt were detected by western blot analysis. 2-Deoxyglucose uptake was measured in LAR knockdown and control cells using d-[2-3H]glucose. LAR protein level was decreased by 65% in the stable cell line compared with the control cells. Palmitate (0.5 mM) significantly induced LAR mRNA (65%) and protein levels (40%) in myotubes compared with untreated cells. Palmitate significantly reduced insulin-stimulated glucose uptake in both the control and LAR knockdown cells by 33 and 51% respectively. However, LAR depletion improved insulin-stimulated glucose uptake in myotubes treated with palmitate. Furthermore, the inhibition of LAR prevented palmitate-induced decreases in phosphorylation of IRS1Tyr632 and AktSer473 in C2C12 cells. In conclusion, these results reveal that palmitate induces LAR expression in C2C12 cells. We also provided evidence that the inhibition of LAR attenuates palmitate-induced insulin resistance in myotubes.

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

Botanical Studies ◽

10.1186/s40529-021-00315-8 ◽

2021 ◽

Vol 62 (1) ◽

Author(s):

Lie-Fen Shyur ◽

Viola Varga ◽

Chiao-Ming Chen ◽

Shu-Chi Mu ◽

Yu-Chih Chang ◽

...

Keyword(s):

Insulin Resistance ◽

Ethyl Acetate ◽

Glucose Uptake ◽

Sweet Potato ◽

Akt Pathway ◽

C2c12 Myotubes ◽

Total Phenolic ◽

C2c12 Myoblast ◽

Dependent Manner ◽

Tnf Α

Abstract Background White sweet potato (WSP; Ipomoea 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) was partitioned with ethyl-acetate and water to obtain ethyl-acetate layer (WSP-EA) and water layer (WSP-EW). The WSP-EA shows the highest total phenolic contents and highest antioxidant activity by Folin-Ciocalteu and (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH) assay, respectively. After low concentration horse serum on differentiation inducement of C2C12 myoblasts into mature myotubes, the cells were treated with TNF-α to induce insulin resistance. 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-dependent manner as examined 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. The in vitro data reveal that WSP tuber extracts has potential applications to improve insulin resistance in diabetes.

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