Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition

Li, H.B.; Yang, Yan; Mo, Zejun; Ding, Ye; Jiang, Wei

doi:10.1590/1414-431x20144238

Cited by 57 publications

(40 citation statements)

References 33 publications

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“…This effect can be decreased by many natural substances like silibinin (principal flavonoid contained in silymarin, a mixture of flavonolignans extracted from Silybum marianum seeds). Silibinin prevents PI3K/AKT pathway inhibition by decreasing IRS1 phosphorylation on Tyr [24]. Similar mechanism is typical of PTP1B (protein-tyrosine phosphatase 1B), whose overexpression can inactivate the whole PI3K pathway [25].…”

Section: Irs Protein Nodementioning

confidence: 71%

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Świderska¹,

Strycharz²,

Wróblewski³

et al. 2020

Blood Glucose Levels

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Glucose uptake is regulated by several mechanisms, where insulin plays the most prominent role. This powerful anabolic hormone regulates the transport of glucose into the cell through translocation of glucose transporter from an intracellular pool to the plasma membrane mainly in metabolically active tissues like skeletal muscles, adipose tissue, or liver (GLUT4). This translocation occurs through multiple steps of PI3K/AKT signaling pathway. In this chapter, we will focus on molecular events leading to GLUT4 translocation, starting with activation of insulin receptors through signaling cascade involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) and finally, the action of their effectors. We will present regulatory mechanisms and modulators of insulin-mediated glucose uptake.

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Section: Irs Protein Nodementioning

confidence: 71%

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Świderska¹,

Strycharz²,

Wróblewski³

et al. 2020

Blood Glucose Levels

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“…It is widely known that insulin stimulates the Akt canonical pathway under physiological conditions [Li et al, ]. Phosphorylation of Akt at Ser 473 indicates the increment in insulin signaling by the ADSCs‐CM when compared to the diseases conditioned in C2C12 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models

Shree

Bhonde

2017

J. Cell. Biochem.

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The link between insulin resistance (IR) and type 2 diabetes has been recognized for a long time. Type 2 diabetes is often associated with basal hyperinsulinemia, reduced sensitivity to insulin, and disturbances in insulin release. There are evidences showing the reversal of IR by mesenchymal stem cells. However, the effect of conditioned media from adipose derived mesenchymal stem cells (ADSCs-CM) in reversal of IR has not been established. We established an insulin resistant model of 3T3L1 and C2C12 cells and treated with ADSCs-CM. 2-NBDG (2-[N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]Amino]-2-Deoxyglucose) uptake was performed to assess improvement in glucose uptake. Genes involved in glucose transport and in inflammation were also analysed. Western blot for glucose transporter-4 and Akt was performed to evaluate translocation of Glut4 and insulin signaling respectively. We found that the ADSCs-CM treated cells restored insulin, stimulated glucose uptake as compared to the untreated control indicating the insulin sensitizing effect of the CM. The treated cells also showed inhibition adipogenesis in 3T3L1 cells and significant reduction of intramuscular triglyceride accumulation in C2C12 cells. Gene expressions studies revealed the drastic upregulation of GLUT4 gene and significant reduction in IL6 and PAI1 gene in both 3T3L1 and C2C12 cells, indicating possible mechanism of glucose uptake with concomitant decrease in inflammation. Enhancement of GLUT4 and phospho Akt protein expression seems to be responsible for the increment in glucose uptake and enhanced insulin signaling, respectively. Our study revealed for the first time that ADSCs-CM acts as an alternative insulin sensitizer providing stem cell solution to IR. J. Cell. Biochem. 118: 2037-2043,2017. © 2016 Wiley Periodicals, Inc.

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“…Our results ( Figure 5 ) demonstrated that CmNo1 treatment leads to both the increased phosphorylation and enhanced expression of insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT-4), indicating that the activated mediators subsequently increased insulin sensitivity. Many previous studies have already demonstrated the activation of IRS-1 and AKT via phosphorylation and GLUT-4 translocation as indicators of insulin sensitivity [ 55 – 60 ]. Additionally, high expression of GLUT-4 has also been reported to promote insulin-mediated glucose uptake [ 32 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia ofCordyceps militarisin High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice

Chen

et al. 2015

Journal of Diabetes Research

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Diabetes mellitus (DM) is currently ranked among leading causes of death worldwide in which type 2 DM is reaching an epidemic proportion. Hypoglycemic medications for type 2 DM have either proven inadequate or posed adverse effects; therefore, the Chinese herbal products are under investigation as an alternative treatment. In this study, a novel combination of fruiting body and mycelia powder of herbal Cordyceps militaris number 1 (CmNo1) was administered to evaluate their potential hypoglycemic effects in high-fat diet- (HFD-) induced type 2 DM in C57BL/6J mice. Body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and blood biochemistry indexes were measured. Results indicated that CmNo1 lowered the blood glucose level by increasing insulin sensitivity, while no change in body weight was observed. Increased protein expression of IRS-1, pIRS-1, AKT, pAKT, and GLUT-4 in skeletal muscle and adipose tissue was found indicating restoration of insulin signaling. Additionally, PPAR-γ expression in adipose tissue restored the triglyceride and cholesterol levels. Finally, our results suggest that CmNo1 possesses strong hypoglycemic, anticholesterolemic, and antihypertriglyceridemic actions and is more economical alternate for DM treatment.

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Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition

Cited by 57 publications

References 33 publications

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models

Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia ofCordyceps militarisin High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice

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