scholarly journals Extracellular ATP Increases Glucose Metabolism in Skeletal Muscle Cells in a P2 Receptor Dependent Manner but Does Not Contribute to Palmitate-Induced Insulin Resistance

2020 ◽  
Vol 11 ◽  
Author(s):  
Ana Miguel Cruz ◽  
Craig Beall
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Muscle Cells ◽  
Extracellular Atp ◽  
Skeletal Muscle Cells ◽  
Dependent Manner ◽  
P2 Receptor

A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling

Pharmacology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Bhavimani Guru ◽  
Akhilesh K. Tamrakar ◽  
Subhankar P. Mandal ◽  
Prashantha B.R. Kumar ◽  
Aditya Sharma ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Molecular Docking ◽  
Md Simulation ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Dependent Manner ◽  
Glut4 Translocation ◽  
Binding Interactions ◽  
Pparγ Agonists

<b><i>Introduction:</i></b> Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are highly effective in treating insulin resistance. However, associated side effects such as weight gain due to increase in adipogenesis and lipogenesis hinder their clinical use. The aim of the study was to design and synthesize novel partial PPARγ agonists with weaker lipogenic effect in adipocytes and enhanced glucose transporter 4 (GLUT4) translocation stimulatory effect in skeletal muscle cells. <b><i>Methods:</i></b> Novel partial PPARγ agonists (GS1, GS2, and GS3) were designed and screened to predict their binding interactions with PPARγ by molecular docking. The stability of the docked ligand-PPARγ complex was studied by molecular dynamics (MD) simulation. The cytotoxicity of synthesized compounds was tested in 3T3-L1 adipocytes and L6 myoblasts by MTT assay. The lipogenic effect was investigated in 3T3-L1 adipocytes using oil red O staining and GLUT4 translocation stimulatory effect in L6-GLUT4<i>myc</i> myotubes by an antibody-coupled colorimetric assay. <b><i>Results:</i></b> The molecular docking showed the binding interactions between designed agonists and PPARγ. MD simulation demonstrated good stability between the GS2-PPARγ complex. GS2 and GS3 did not show any significant effect on cell viability up to 80 or 100 μM concentration. Pioglitazone treatment significantly increased intracellular lipid accumulation in adipocytes compared to control. However, this effect was significantly less in GS2- and GS3-treated conditions compared to pioglitazone at 10 μM concentration, indicating weaker lipogenic effect. Furthermore, GS2 significantly stimulated GLUT4 translocation to the plasma membrane in a dose-dependent manner via the AMPK-dependent signaling pathway in skeletal muscle cells. <b><i>Conclusion:</i></b> GS2 may be a promising therapeutic agent for the treatment of insulin resistance and type 2 diabetes mellitus without adiposity.

Extracts of Hymenocardia acida ameliorate insulin resistance in skeletal muscle cells

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
II Ezeigbo ◽  
C Wheeler-Jones ◽  
S Gibbons ◽  
ME Cleasby
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Ameliorate Insulin Resistance

scholarly journals Adiponectin improves insulin sensitivity via activation of autophagic flux

2017 ◽  
Vol 59 (4) ◽  
pp. 339-350 ◽  
Author(s):  
Penny Ahlstrom ◽  
Esther Rai ◽  
Suharto Chakma ◽  
Hee Ho Cho ◽  
Palanivel Rengasamy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Er Stress ◽  
Western Blotting ◽  
Muscle Cells ◽  
Dominant Negative ◽  
Skeletal Muscle Cells ◽  
Dominant Negative Mutant ◽  
Autophagic Flux

Skeletal muscle insulin resistance is known to play an important role in the pathogenesis of diabetes, and one potential causative cellular mechanism is endoplasmic reticulum (ER) stress. Adiponectin mediates anti-diabetic effects via direct metabolic actions and by improving insulin sensitivity, and we recently demonstrated an important role in stimulation of autophagy by adiponectin. However, there is limited knowledge on crosstalk between autophagy and ER stress in skeletal muscle and in particular how they are regulated by adiponectin. Here, we utilized the model of high insulin/glucose (HIHG)-induced insulin resistance, determined by measuring Akt phosphorylation (T308 and S473) and glucose uptake in L6 skeletal muscle cells. HIHG reduced autophagic flux measured by LC3 and p62 Western blotting and tandem fluorescent RFP/GFP-LC3 immunofluorescence (IF). HIHG also induced ER stress assessed by thioflavin T/KDEL IF, pIRE1, pPERK, peIF2α and ATF6 Western blotting and induction of a GRP78-mCherry reporter. Induction of autophagy by adiponectin or rapamycin attenuated HIHG-induced ER stress and improved insulin sensitivity. The functional significance of enhanced autophagy was validated by demonstrating a lack of improved insulin sensitivity in response to adiponectin in autophagy-deficient cells generated by overexpression of dominant negative mutant of Atg5. In summary, adiponectin-induced autophagy in skeletal muscle cells alleviated HIHG-induced ER stress and insulin resistance.

Metformin ameliorates high uric acid-induced insulin resistance in skeletal muscle cells

2017 ◽  
Vol 443 ◽  
pp. 138-145 ◽  
Author(s):  
Huier Yuan ◽  
Yaqiu Hu ◽  
Yuzhang Zhu ◽  
Yongneng Zhang ◽  
Chaohuan Luo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Uric Acid ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
High Uric Acid

scholarly journals Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

2012 ◽  
Vol 11 (1) ◽  
pp. 36 ◽  
Author(s):  
Keisuke Sawada ◽  
Kyuichi Kawabata ◽  
Takatoshi Yamashita ◽  
Kengo Kawasaki ◽  
Norio Yamamoto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Palmitic Acid ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
L6 Skeletal Muscle Cells
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