p38 MAPK ATTENUATES INSULIN SIGNALING BY INHIBITING IRS1 TYROSINE PHOSPHORYLATION IN IRS1 OVEREXPRESSED 293T CELLS

Year 2020, Volume: 13 Issue: 1, 19 - 24, 30.04.2020

Gökhan Görgişen Osman Nidai Ozes

Abstract

Objective: The aim of this study was to investigate the effect of p38 MAPK on insulin signaling in IRS1 overexpressed 293T cells.
Materials and Methods: 293T cells were transfected with pcDNA3.1flag-tagged-human-IRS1 expression vector. Anisomycin and SB203580 were used as p38 MAPK activator and inhibitor respectively. Expression and phosphorylation profiles of IRS1, AKT and ERK1/2 were detected by western blotting.
Results: Anisomycin treatment led to decrease in insulin induced tyrosine phosphorylation of IRS1 through Ser/Thr phosphorylations. We also detected insulin induced AKT and ERK1/2 phosphorylations reduced by anisomycin compared to insulin treated group. We observed that negative effects of anisomycin on insulin signaling reversed by the treatment of SB203580.
Conclusion: p38 MAPK inhibits the phosphorylations of IRS1, AKT and ERK1/2. p38 MAPK may serve as a therapeutic target for insulin resistance and specific p38 MAPK inhibitors might be potential and promising agents for the therapeutic approaches.

Keywords

p38 MAPK, IRS1, Insulin signaling, Insulin resistance

Supporting Institution

Akdeniz University, The Scientific Research Projects Coordination Unit

Project Number

2012.03.0122.004

Thanks

This study was supported by a grant from Akdeniz University, The Scientific Research Projects Coordination Unit (Project No: 2012.03.0122.004), Antalya, Turkey.

p38 MAPK, IRS1 EKSPRESYONU ARTTIRILMIŞ 293T HÜCRELERİNDE IRS1 TİROZİN FOSFORİLASYONUNU İNHİBE EDEREK İNSÜLİN SİNYALİNİ YAVAŞLATMAKTADIR

Abstract

Amaç: Bu çalışmanın amacı IRS1 ekspresyonu arttırılmış 293T hücrelerinde p38 MAPK’ ın insülin sinyali üzerindeki etkisinin belirlenmesidir.
Materyal Metod: 293T hücreleri pcDNA3.1flag-tagged-insan-IRS1 ekspresyon vektörü ile transfekte edilmiştir. P38 MAPK inhibitörü ve aktivatörü olarak sırasıyla anisomisin ve SB203580 kullanılmıştır. IRS1, AKT ve ERK1/2 ekspresyon ve aktivasyon profilleri western blot ile belirlenmiştir.
Bulgular: Anisomisin muamelesi IRS1 Ser/Thr fosforilasyonu aracılığıyla insülin indüklü IRS1 tirozin fosforilasyonunu azalmıştır. Anisomisin muamele grupta kontrol grubuna oranla insülin indüklü AKT ve ERK1/2 fosforilasyonunda da azalma olduğu belirlenmiştir. Anisomisinin insülin sinyali üzerindeki negatif etkilerinin SB203580 muamelesi ile geri döndürüldüğü gözlemlenmiştir.
Sonuç: p38 MAPK, IRS1, AKT ve ERK1/2 fosforilasyonlarını inhibe etmektedir. P38 MAPK, insülin direncinde terapötik hedef olarak kullanılabilir ve spesifik p38 MAPK inhibitörleri, terapötik yaklaşımlar için potansiyel ve umut verici ajanlar olabilir.

Keywords

p38 MAPK, IRS1, İnsülin sinyali, İnsülin direnci

Project Number

2012.03.0122.004

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