scholarly journals Effect of Phyllanthus emblica L. fruit on improving regulation of methylglyoxal-induced insulin resistance in 3T3-L1 cells

2018 ◽  
Vol 4 ◽  
Author(s):  
Hui-Chi Chen ◽  
Yu-Tang Tung ◽  
Sheng-Yi Chen ◽  
Jer-An Lin ◽  
Gow-Chin Yen
Keyword(s):  
Insulin Resistance ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Ellagic Acid ◽  
Tyrosine Phosphatase ◽  
Water Extract ◽  
Peroxisome Proliferator ◽  
Phyllanthus Emblica ◽  
Fat Accumulation ◽  
Increase Glucose Uptake

The increasing methylglyoxal (MG) level of body has been found in people with obesity and insulin resistance, resulting from their dietary style and abnormal metabolic functions. MG promotes inflammation, oxidative stress, glycation, and all of which are closely related to insulin resistance and chronic diseases. Phyllanthus emblica L. fruit has various bioactivities such as anti-inflammation, anti-diabetes, anti-nonalcoholic fatty liver, and anti-dyslipidemia. Therefore, this study was aimed to investigate the effects of water extract of P. emblica (WEPE) and its enriched compound, ellagic acid, on MG-induced inflammation, insulin resistance, and lipogenesis in 3T3-L1 cells. The results showed that MG activated the peroxisome proliferator activated receptor-gamma (PPARγ) and CCAAT/ enhancer-binding protein alpha (C/EBPα), which can increase adipogenesis in adipocytes. In addition, MG enhanced pro-inflammatory cytokine IL-6 protein expression and release through the activation of MAPK and NF-κB signaling pathway, as well as increasing the monocyte chemoattractant protein-1 expression to cause macrophage infiltration. MG also significantly reduced glucose uptake, indicating that insulin resistance in obese patients may be related to MG generation. WEPE and ellagic acid effectively decreased IL-6 protein expression and cytokine release through inactivation of JNK and p65 pathways. WEPE and ellagic acid significantly increased glucose uptake and reduced insulin resistance by MG treatment. WEPE also decreased the protein-tyrosine phosphatase 1B to reduce insulin resistance and inhibited MG-induced fat accumulation related proteins such as PPARγ, C/EBPα, FAS, and p-ACC. Therefore, WEPE may have the potential to ameliorate MG-induced inflammation, increase glucose uptake, and decrease fat accumulation.

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

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.

scholarly journals Inhibition of the Protein Tyrosine Phosphatase SHP-1 Increases Glucose Uptake in Skeletal Muscle Cells by Augmenting Insulin Receptor Signaling and GLUT4 Expression

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4581-4588 ◽  
Author(s):  
Sébastien Bergeron ◽  
Marie-Julie Dubois ◽  
Kerstin Bellmann ◽  
Michael Schwab ◽  
Nancy Larochelle ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Protein Tyrosine Phosphatase ◽  
Insulin Action ◽  
Tyrosine Phosphatase ◽  
Glycogen Synthesis ◽  
Glut4 Translocation ◽  
Protein Tyrosine ◽  
Glut4 Expression

The protein tyrosine phosphatase (PTPase) Src-homology 2-domain-containing phosphatase (SHP)-1 was recently reported to be a novel regulator of insulin's metabolic action. In order to examine the role of this PTPase in skeletal muscle, we used adenovirus (AdV)-mediated gene transfer to express an interfering mutant of SHP-1 [dominant negative (DN)SHP-1; mutation C453S] in L6 myocytes. Expression of DNSHP-1 increased insulin-induced Akt serine-threonine kinase phosphorylation and augmented glucose uptake and glycogen synthesis. Pharmacological inhibition of glucose transporter type 4 (GLUT4) activity using indinavir and GLUT4 translocation assays revealed an important role for this transporter in the increased insulin-induced glucose uptake in DNSHP-1-expressing myocytes. Both GLUT4 mRNA and protein expression were also found to be increased by DNSHP-1 expression. Furthermore, AdV-mediated delivery of DNSHP-1 in skeletal muscle of transgenic mice overexpressing Coxsackie and AdV receptor also enhanced GLUT4 protein expression. Together, these findings confirm that SHP-1 regulates muscle insulin action in a cell-autonomous manner and further suggest that the PTPase negatively modulates insulin action through down-regulation of both insulin signaling to Akt and GLUT4 translocation, as well as GLUT4 expression.

scholarly journals Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle

2018 ◽  
Vol 125 (2) ◽  
pp. 596-604 ◽  
Author(s):  
Emi Kawamoto ◽  
Keigo Tamakoshi ◽  
Song-Gyu Ra ◽  
Hiroyuki Masuda ◽  
Kentaro Kawanaka
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Rapid Development ◽  
Plaster Cast ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Transcription Inhibitor ◽  
Male Wistar Rats

Acute short duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Because thioredoxin-interacting protein (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-h hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral nonimmobilized hindlimbs were excised and examined. The 6-h immobilization resulted in an increase in TXNIP mRNA and protein expressions together with a decrease in insulin-stimulated 2-deoxyglucose uptake in the rat soleus muscle. Additionally, in the rats euthanized 6 h after the plaster cast removal, TXNIP protein expression and insulin-stimulated glucose uptake in the immobilized muscle had both been restored to a normal level. Various interventions (pretreatment with transcription inhibitor actinomycin D or AMP-dependent protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleotide) also suppressed the increase in TXNIP protein expression in 6-h-immobilized muscle together with partial prevention of insulin resistance for glucose uptake. These results suggested the possibility that increased TXNIP protein expression in immobilized rat soleus muscles was associated with the rapid induction of insulin resistance for glucose uptake in that tissue. NEW & NOTEWORTHY The cellular mechanism by which disuse rapidly induces muscle insulin resistance for glucose uptake remains to be identified. Using a rat hindlimb immobilization model, our findings suggest the possibility that transcriptional upregulation of thioredoxin-interacting protein is associated with the immobilization-induced rapid development of insulin resistance in skeletal muscle.

scholarly journals Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoyan Sheng ◽  
Yuebo Zhang ◽  
Zhenwei Gong ◽  
Cheng Huang ◽  
Ying Qin Zang
Keyword(s):  
Insulin Resistance ◽  
Target Genes ◽  
Water Extract ◽  
Food Preparation ◽  
Peroxisome Proliferator ◽  
Cinnamon Extract ◽  
Diet Induced Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
High Caloric Diet

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARγandα, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO) anddb/dbmice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptorsγandα(PPARγ/α) and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD) of PPARγand PPARαare activated by cinnamon as evidenced by reporter gene assays. These data suggest that cinnamon in its water extract form can act as a dual activator of PPARγandα, and may be an alternative to PPARγactivator in managing obesity-related diabetes and hyperlipidemia.

scholarly journals Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2023 ◽  
Author(s):  
Junnan Ma ◽  
Seok Yong Kang ◽  
Xianglong Meng ◽  
An Na Kang ◽  
Jong Hun Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Mitochondrial Biogenesis ◽  
Water Extract ◽  
Sirtuin 1 ◽  
Myoblast Differentiation ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dioscorea Batatas

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.

scholarly journals Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death

2008 ◽  
Vol 29 (2) ◽  
pp. 378-388 ◽  
Author(s):  
Frederic Princen ◽  
Emilie Bard ◽  
Farah Sheikh ◽  
Sharon S. Zhang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Dilated Cardiomyopathy ◽  
Glucose Uptake ◽  
Single Molecule ◽  
Intracellular Signaling ◽  
Striated Muscle ◽  
Tyrosine Phosphatase ◽  
Premature Mortality ◽  
Premature Death ◽  
Metabolic Disturbances

ABSTRACT The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-ζ/λ and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones.

Bioactive Components from Flowers ofSambucus nigraL. Increase Glucose Uptake in Primary Porcine Myotube Cultures and Reduce Fat Accumulation inCaenorhabditis elegans

2013 ◽  
Vol 61 (46) ◽  
pp. 11033-11040 ◽  
Author(s):  
Sumangala Bhattacharya ◽  
Kathrine B. Christensen ◽  
Louise C. B. Olsen ◽  
Lars P. Christensen ◽  
Kai Grevsen ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Bioactive Components ◽  
Fat Accumulation ◽  
Increase Glucose Uptake

P0986NO/CGMP PATHWAY MODULATES GLUCOSE UPTAKE VIA REGULATION OF SIRT1 DEACETYLASE EXPRESSION AND ACTIVITY IN PODOCYTES EXPOSED TO HIGH GLUCOSE CONCENTRATIONS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dorota Rogacka ◽  
Irena Audzeyenka ◽  
Agnieszka Piwkowska
Keyword(s):  
Insulin Resistance ◽  
Protein Expression ◽  
Glucose Uptake ◽  
High Glucose ◽  
Sirtuin 1 ◽  
Insulin Effect ◽  
Cgmp Pathway ◽  
Pathway Inhibition ◽  
And Function ◽  
Expression And Activity

Abstract Background and Aims Glomerular podocytes have become the aim of the extensive research in diabetes because of their importance in the development of diabetic nephropathy. High glucose concentration affects podocyte metabolism and function leading to the development of insulin resistance. Moreover, it decreases deacetylase SIRT1 protein amount and activity, leading to abolition of insulin effect on glucose uptake into the cells. The aim of our study was to examine the involvement of NO/cGMP pathway in the regulation of sirtuin 1 (SIRT1) protein expression and activity in podocytes, in the context of high-glucose induced insulin resistance. This work was supported by grant from the National Science Centre (2016/23/B/NZ4/03448). Method Experiments were performed in primary rat podocytes cultured with normal (NG, 11.1 mM) or high (HG, 30 mM) glucose concentrations for 5 days. RT-PCR and immunodetection methods were used to detect mRNA and protein expressions. Glucose uptake was measured by the addition of 1 µCi/well of 2-deoxy-(1,2-3H)-D-glucose uptake diluted in non-radioactive dglucose (50 µM final concentration) with or without 300 nM insulin. SIRT1 activity was determined with a SIRT1 Fluorometric Kit according to the manufacturer’s instructions. SIRT1 expression was modified by transfection with SIRT1 siRNA. To examine the effect of NO/cGMP pathway activity on SIRT1, cells were incubated in the presence of SNAP, a mimetic of nitric oxide synthase activity (NOS), and 8-Br-cGMP, protein kinase G (PKG) activator. We also used L-NAME – NOS inhibitor, and Rp-8-Br-cGMPs, PKG inhibitor. Results SIRT1 protein expression and activity were decreased in podocytes exposed to high glucose concentrations. We showed that in the presence of SNAP and 8-Br-cGMP, SIRT1 protein amount and activity were increased, leading also to enhancement of basal and insulin-dependent glucose uptake. In podocytes, transfected with SIRT1 siRNA, treatment with NO/cGMP pathway activators SNAP or 8-Br-cGMP increased glucose uptake. NO/cGMP pathway inhibitors exerted opposite effects on SIRT1 protein level and activity as well as on glucose uptake. Insulin action on glucose uptake into podocytes cultivated in the presence of normal glucose concentrations was abolished after NO/cGMP pathway inhibition. Conclusion We found that impairment of insulin effect on glucose uptake in HG-exposed podocytes, which was associated with SIRT1 downregulation, may be prevented by NO-dependent signaling modulation.

scholarly journals Screening for Bioactive Metabolites in Plant Extracts Modulating Glucose Uptake and Fat Accumulation

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Rime B. El-Houri ◽  
Dorota Kotowska ◽  
Louise C. B. Olsen ◽  
Sumangala Bhattacharya ◽  
Lars P. Christensen ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Adipocyte Differentiation ◽  
Independent Effect ◽  
Bioactive Metabolites ◽  
Thymus Vulgaris ◽  
Peroxisome Proliferator ◽  
Fat Accumulation ◽  
Methanol Extracts ◽  
Insulin Dependent ◽  
Screening Platform

Dichloromethane and methanol extracts of seven different food and medicinal plants were tested in a screening platform for identification of extracts with potential bioactivity related to insulin-dependent glucose uptake and fat accumulation. The screening platform included a series ofin vitrobioassays, peroxisome proliferator-activated receptor (PPAR)γ-mediated transactivation, adipocyte differentiation of 3T3-L1 cell cultures, and glucose uptake in both 3T3-L1 adipocytes and primary porcine myotubes, as well as onein vivobioassay, fat accumulation in the nematodeCaenorhabditis elegans. We found that dichloromethane extracts of aerial parts of golden root (Rhodiola rosea) and common elder (Sambucus nigra) as well as the dichloromethane extracts of thyme (Thymus vulgaris) and carrot (Daucus carota) were able to stimulate insulin-dependent glucose uptake in both adipocytes and myotubes while weekly activating PPARγwithout promoting adipocyte differentiation. In addition, these extracts were able to decrease fat accumulation inC. elegans. Methanol extracts of summer savory (Satureja hortensis), common elder, and broccoli (Brassica oleracea) enhanced glucose uptake in myotubes but were not able to activate PPARγ, indicating a PPARγ-independent effect on glucose uptake.

scholarly journals Phloridzin Acts as an Inhibitor of Protein-Tyrosine Phosphatase MEG2 Relevant to Insulin Resistance

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1612
Author(s):  
Sun-Young Yoon ◽  
Jae Sik Yu ◽  
Ji Young Hwang ◽  
Hae Min So ◽  
Seung Oh Seo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Muscle Cells ◽  
Protein Tyrosine ◽  
C2c12 Muscle Cells

Inhibition of the megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2, also named PTPN9) activity has been shown to be a potential therapeutic strategy for the treatment of type 2 diabetes. Previously, we reported that PTP-MEG2 knockdown enhances adenosine monophosphate activated protein kinase (AMPK) phosphorylation, suggesting that PTP-MEG2 may be a potential antidiabetic target. In this study, we found that phloridzin, isolated from Ulmus davidiana var. japonica, inhibits the catalytic activity of PTP-MEG2 (half-inhibitory concentration, IC50 = 32 ± 1.06 μM) in vitro, indicating that it could be a potential antidiabetic drug candidate. Importantly, phloridzin stimulated glucose uptake by differentiated 3T3-L1 adipocytes and C2C12 muscle cells compared to that by the control cells. Moreover, phloridzin led to the enhanced phosphorylation of AMPK and Akt relevant to increased insulin sensitivity. Importantly, phloridzin attenuated palmitate-induced insulin resistance in C2C12 muscle cells. We also found that phloridzin did not accelerate adipocyte differentiation, suggesting that phloridzin improves insulin sensitivity without significant lipid accumulation. Taken together, our results demonstrate that phloridzin, an inhibitor of PTP-MEG2, stimulates glucose uptake through the activation of both AMPK and Akt signaling pathways. These results strongly suggest that phloridzin could be used as a potential therapeutic candidate for the treatment of type 2 diabetes.

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