Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

The key role of akt protein kinase in metabolic-inflammatory pathways cross-talk: Tnf-α down-regulation and improving of insulin resistance in hepg2 cell line

Thu Aug 18 12:15:43 2022

(2021) The key role of akt protein kinase in metabolic-inflammatory pathways cross-talk: Tnf-α down-regulation and improving of insulin resistance in hepg2 cell line. Current Molecular Medicine. pp. 257-264. ISSN 15665240 (ISSN)

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

Abstract

Background: Elevation of plasma free fatty acids as a principal aspect of type 2 diabetes maintains etiologically insulin insensitivity in target cells. TNF-α inhibitory effects on key insulin signaling pathway elements remain to be verified in insulin-resistant hepatic cells. Thus, TNF-α knockdown effects on the key elements of insulin signaling were investigated in the palmitate-induced insulin-resistant hepatocytes. The Akt serine kinase, a key protein of the insulin signaling pathway, phosphorylation was monitored to understand the TNF-α effect on probable enhancing of insulin resistance. Methods: Insulin-resistant HepG2 cells were produced using 0.5 mM palmitate treatment and shRNA-mediated TNF-α gene knockdown and its down-regulation confirmed using ELISA technique. Western blotting analysis was used to assess the Akt protein phosphorylation status. Results: Palmitate-induced insulin resistance caused TNF-α protein overexpression 1.2-, 2.78, and 2.25-fold as compared to the control cells at post-treatment times of 8 h, 16 h, and 24 h, respectively. In the presence of palmitate, TNF-α expression showed around 30 reduction in TNF-α knockdown cells as compared to normal cells. In the TNF-α down-regulated cell, Akt phosphorylation was approximately 62 more than control cells after treatment with 100 nM insulin in conjugation with 0.5 mM palmitate. Conclusions: The obtained data demonstrated that TNF-α protein expression reduction improved insulin-stimulated Akt phosphorylation in the HepG2 cells and decreased lipid-induced insulin resistance of the diabetic hepatocytes. © 2021 Bentham Science Publishers.

Item Type: Article
Creators:
CreatorsEmail
Alipourfard, I.UNSPECIFIED
Bakhtiyari, S.UNSPECIFIED
Gheysarzadeh, A.UNSPECIFIED
Di Renzo, L.UNSPECIFIED
De Lorenzo, A.UNSPECIFIED
Mikeladze, D.UNSPECIFIED
Khamoushi, A.UNSPECIFIED
Keywords: Akt kinase Diabetes HepG2 cell Insulin resistance Palmitate TNF-α
Divisions:
Page Range: pp. 257-264
Journal or Publication Title: Current Molecular Medicine
Journal Index: Scopus
Volume: 21
Number: 3
Identification Number: https://doi.org/10.2174/1566524020666200427102209
ISSN: 15665240 (ISSN)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/3498

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