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

R. Chao1,a*, D. Li1, Z. Yue1, C. Huang1, Y. Kou1, Q. Zhou1, Y. Gao1, T. Hasegawa2, J. Guo1, and M. Li1,b*

1Department 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, 250012 Jinan, China

2Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, 060-8586 Sapporo, Japan

* To whom correspondence should be addressed.

Received October 14, 2019; Revised November 30, 2019; Accepted December 31, 2019
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.
KEY WORDS: obesity, insulin resistance, interleukin-4, osteoblast

DOI: 10.1134/S0006297920030098