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

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R. Chao^1,a*, D. Li¹, Z. Yue¹, C. Huang¹, Y. Kou¹, Q. Zhou¹, Y. Gao¹, T. Hasegawa², J. Guo¹, and M. Li^1,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

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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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KEY WORDS: obesity, insulin resistance, interleukin-4, osteoblast

DOI: 10.1134/S0006297920030098

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