PT  - JOURNAL ARTICLE
AU  - Yang, Peilang
AU  - Wang, Xiqiao
AU  - Wang, Di
AU  - Shi, Yan
AU  - Zhang, Meng
AU  - Yu, Tianyi
AU  - Liu, Dan
AU  - Gao, Min
AU  - Zhang, Xiong
AU  - Liu, Yan
TI  - Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization
AID  - 10.1242/jcs.235838
DP  - 2020 Oct 01
TA  - Journal of Cell Science
PG  - jcs235838
VI  - 133
IP  - 19
4099  - http://jcs.biologists.org/content/133/19/jcs235838.short
4100  - http://jcs.biologists.org/content/133/19/jcs235838.full
SO  - J. Cell Sci.2020 Oct 01; 133
AB  - 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.