Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

Investigating the effects of TNF-α knockdown gene on insulin resistance in C2C12 muscle cells in the presence and absence of palmitate

Sun Aug 14 02:07:53 2022

(2013) Investigating the effects of TNF-α knockdown gene on insulin resistance in C2C12 muscle cells in the presence and absence of palmitate. Iranian Journal of Endocrinology and Metabolism. pp. 387-394. ISSN 16834844 (ISSN)

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Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Abstract

Introduction: Insulin resistance plays a major role in type 2 diabetes and obesity. In this disorder, lipid accumulation is accompanied by increased TNF-α expression in the muscle. The aims of this study were to evaluate the effects of tumor necrosis factor-α (TNF-α) gene knockdown on key elements of insulin signaling pathway (IRS-1 and Akt) and insulin resistance in C2C12 muscle cells in the presence and absence of palmitate. Materials and Methods: To knockdown protein expression of TNF-α, the C2C12 cells were transfected with the shRNA containing antisense sequence of murine TNF-α gene. The analysis of TNF-α protein expression and phosphorylation and protein levels of IRS-1and Akt were subsequently detected by western blot. Results: In TNF-α knockdown cells, the protein expression level of TNF-α was reduced by 58. Under treatment with palmitate, insulin stimulated phosphorylation of IRS-1 (Tyr632) and Akt (Ser473) in knockdown cells was increased 1.7 and 2.6 fold, respectively, compared to the controls. Conclusions: Our findings showed that decreasing the TNF-α protein level can enhance the activity of the important elements of insulin signaling pathway (IRS-1 and Akt), leading to the improvement of insulin resistance in myotubes, data suggesting that TNF-α may potentially be a therapeutic target for fatty acid induced insulin resistance observed in type 2 diabetes and metabolic syndrome.

Item Type: Article
Creators:
CreatorsEmail
Pashaei, S.UNSPECIFIED
Bakhtiyari, S.UNSPECIFIED
Haghani, K.UNSPECIFIED
Maleki, F.UNSPECIFIED
Keywords: Insulin resistance Knockdown Palmitate Short hairpin RNA interference Tumor necrosis factor-alpha insulin receptor substrate 1 palmitic acid protein kinase B short hairpin RNA tumor necrosis factor alpha animal cell article controlled study gene silencing genetic transfection muscle cell myotube non insulin dependent diabetes mellitus nonhuman protein expression protein phosphorylation Western blotting
Divisions:
Page Range: pp. 387-394
Journal or Publication Title: Iranian Journal of Endocrinology and Metabolism
Journal Index: Scopus
Volume: 15
Number: 4
ISSN: 16834844 (ISSN)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/1578

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