2. Academic Validation
  3. Interleukin-4 Restores Insulin Sensitivity in Insulin-Resistant Osteoblasts by Increasing the Expression of Insulin Receptor Substrate 1

Interleukin-4 Restores Insulin Sensitivity in Insulin-Resistant Osteoblasts by Increasing the Expression of Insulin Receptor Substrate 1

  • Biochemistry (Mosc). 2020 Mar;85(3):334-343. doi: 10.1134/S0006297920030098.
R Chao 1,  D Li 2,  Z Yue 2,  C Huang 2,  Y Kou 2,  Q Zhou 2,  Y Gao 2,  T Hasegawa 3,  J Guo 2,  M Li 4
Affiliations

Affiliations

  • 1 Department of Bone Metabolism, School and Hospital of Stomatology, Shandong University; Shandong Key Laboratory of Oral Tissue Regeneration; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012, China. chaorui0529@163.com.
  • 2 Department of Bone Metabolism, School and Hospital of Stomatology, Shandong University; Shandong Key Laboratory of Oral Tissue Regeneration; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012, China.
  • 3 Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
  • 4 Department of Bone Metabolism, School and Hospital of Stomatology, Shandong University; Shandong Key Laboratory of Oral Tissue Regeneration; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012, China. liminqi@sdu.edu.cn.
PMID: 32564738 DOI: 10.1134/S0006297920030098
Abstract

Obesity and latent inflammation can give rise to Insulin resistance and type 2 diabetes. Here we established an Insulin resistance model of osteoblasts to explore the restoration effect of anti-inflammatory interleukin-4 (IL-4) on Insulin sensitivity and its mechanism. We found that IL-4 inhibited cell proliferation in a concentration- and time-dependent manner. Insulation resistance significantly reduced the phosphorylation levels of the Insulin Receptor substrate 1 (IRS1; Tyr612), Akt (Ser473), and AS160 (Ser318) proteins. The addition of IL-4 to the Insulin resistance model led to a dose-dependent stimulation of the phosphorylation of IRS1, Akt, and AS160. IL-4 fully restored the activation of the Insulin cascade in insulin-resistant cells at the concentration of 50 ng/ml. Additionally, IL-4 promoted the expression of IRS1 in a time-dependent manner. We conjecture that IL-4 restores Insulin sensitivity in osteoblasts by upregulating the expression of IRS1. It was also found that IL-4 promoted the expression of Osteoprotegerin depending on the time of exposure. This effect may play an important role in the regulation of the energy metabolism in the whole body.

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