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Biochemistry (Moscow)

, Volume 83, Issue 5, pp 498–506 | Cite as

Interleukin-4 Restores Insulin Sensitivity in Lipid-Induced Insulin-Resistant Adipocytes

  • I. S. StafeevEmail author
  • S. S. Michurina
  • N. V. Podkuychenko
  • A. V. VorotnikovEmail author
  • M. Yu. Menshikov
  • Ye. V. Parfyonova
Article

Abstract

Obesity and latent inflammation in adipose tissue significantly contribute to the development of insulin resistance (IR) and type 2 diabetes. Here we studied whether the antiinflammatory interleukin-4 (IL-4) can restore insulin sensitivity in cultured 3T3-L1 adipocytes. The activity of key components of the insulin signaling cascade was assessed by immunoblotting using phospho-specific antibodies to insulin receptor substrate IRS1 (Tyr612), Akt (Thr308 and Ser473), and AS160 (Ser318) protein that regulates translocation of the GLUT4 glucose transporter to the plasma membrane. IR was induced in mature adipocytes with albumin-conjugated palmitate. IR significantly reduced phosphorylation levels of all the above-mentioned proteins. Addition of IL-4 to the culturing medium during IR induction led to a dose-dependent stimulation of the insulin-promoted phosphorylation of IRS1, Akt, and AS160. At the optimal concentration of 50 ng/ml, IL-4 fully restored activation of the insulin cascade in IR cells, but it did not affect insulin signaling activation in the control cells. IL- 4 neither upregulated expression of key adipogenesis markers GLUT4 and PPARγ nor caused lipid accumulation in the adipocytes. These results demonstrate that IL-4 can restore insulin sensitivity in adipocytes via mechanisms not associated with induced adipogenesis or de novo formation of lipid depots.

Keywords

insulin resistance interleukin-4 inflammation 

Abbreviations

Akt

protein kinase B

AS160

Akt substrate of 160 kDa

FBS

fetal bovine serum

GLUT4

type 4 glucose transporter

IKK

IκB kinase

IL-4

interleukin-4

IR

insulin resistance

IRS1

type 1 insulin receptor substrate

PA–BSA

palmitic acid (PA) conjugate with bovine serum albumin (BSA)

PCR

polymerase chain reaction

PDK1

phospho- inositide-dependent protein kinase-1

PPARγ

peroxisome proliferator-activated receptor γ

TLR

Toll-like receptor

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • I. S. Stafeev
    • 1
    • 2
    Email author
  • S. S. Michurina
    • 1
    • 3
  • N. V. Podkuychenko
    • 1
    • 3
  • A. V. Vorotnikov
    • 1
    • 4
    Email author
  • M. Yu. Menshikov
    • 1
  • Ye. V. Parfyonova
    • 1
    • 2
  1. 1.Institute of Experimental CardiologyNational Medical Research Center for CardiologyMoscowRussia
  2. 2.Lomonosov Moscow State UniversityFaculty of Basic MedicineMoscowRussia
  3. 3.Lomonosov Moscow State UniversityFaculty of BiologyMoscowRussia
  4. 4.Lomonosov Moscow State University Medical CenterMoscowRussia

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