Besides regulating glucose levels, insulin has been reported to participate actively in many other functions, including modulating inflammatory reactions. In this study we investigated how topical insulin application would affect the diabetic wound healing process. We found that the excessive expression of insulin-degrading enzyme led to insufficient insulin levels in diabetic skin during wound healing, which ultimately reduced the recovery rate of diabetic wounds. We confirmed that topical insulin application could reverse the impaired inflammation reaction in the diabetic wound environment and promote healing of diabetic wounds. Our study revealed that insulin promoted apoptosis of neutrophils and subsequently triggered polarization of macrophages. Both in vivo and in vitro studies verified that insulin re-established phagocytosis function and promoted the process of phagocytosis-induced apoptosis in neutrophils. Furthermore, we found that insulin treatment also promoted efferocytosis of the apoptosed neutrophils by macrophages, and thus induced macrophages to change their polarization state from M1 to M2. In conclusion, our studies proved that the exogenous application of insulin could improve diabetic wound healing via the restoration of the inflammatory response.

据报道，除了调节血糖水平外，胰岛素还积极参与许多其他功能，包括调节炎症反应。在这项研究中，我们研究了局部胰岛素的应用如何影响糖尿病伤口的愈合过程。我们发现胰岛素降解酶的过度表达导致伤口愈合过程中糖尿病皮肤中胰岛素水平不足，最终降低了糖尿病伤口的恢复率。我们证实，局部应用胰岛素可以逆转糖尿病伤口环境中受损的炎症反应，并促进糖尿病伤口的愈合。我们的研究表明，胰岛素促进中性粒细胞凋亡，随后引发巨噬细胞极化。体内和体外研究均证实胰岛素重新建立了吞噬功能并促进了吞噬诱导中性粒细胞凋亡的过程。此外，我们发现胰岛素治疗还促进巨噬细胞对凋亡中性粒细胞的胞吞作用，从而诱导巨噬细胞将其极化状态从M1改变为M2。总之，我们的研究证明，外源性应用胰岛素可以通过恢复炎症反应来改善糖尿病伤口愈合。