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.

中文翻译：

---

Interleukin-4 通过增加胰岛素受体底物 1 的表达来恢复抗胰岛素成骨细胞的胰岛素敏感性

肥胖和潜在炎症会导致胰岛素抵抗和 2 型糖尿病。在这里，我们建立了成骨细胞的胰岛素抵抗模型，以探讨抗炎性白细胞介素-4（IL-4）对胰岛素敏感性的恢复作用及其机制。我们发现 IL-4 以浓度和时间依赖性方式抑制细胞增殖。绝缘抵抗显着降低了胰岛素受体底物 1 (IRS1; Tyr612)、Akt (Ser473) 和 AS160 (Ser318) 蛋白的磷酸化水平。将 IL-4 添加到胰岛素抵抗模型导致 IRS1、Akt 和 AS160 磷酸化的剂量依赖性刺激。IL-4 在 50 ng/ml 的浓度下完全恢复胰岛素抵抗细胞中胰岛素级联的激活。此外，IL-4 以时间依赖性方式促进 IRS1 的表达。我们推测 IL-4 通过上调 IRS1 的表达来恢复成骨细胞的胰岛素敏感性。还发现IL-4根据暴露时间促进骨保护素的表达。这种作用可能在全身能量代谢的调节中起重要作用。