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


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.


insulin resistance interleukin-4 inflammation 



protein kinase B


Akt substrate of 160 kDa


fetal bovine serum


type 4 glucose transporter


IκB kinase




insulin resistance


type 1 insulin receptor substrate


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


polymerase chain reaction


phospho- inositide-dependent protein kinase-1


peroxisome proliferator-activated receptor γ


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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