RT Journal Article
SR Electronic
T1 Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP jcs235838
DO 10.1242/jcs.235838
VO 133
IS 19
A1 Yang, Peilang
A1 Wang, Xiqiao
A1 Wang, Di
A1 Shi, Yan
A1 Zhang, Meng
A1 Yu, Tianyi
A1 Liu, Dan
A1 Gao, Min
A1 Zhang, Xiong
A1 Liu, Yan
YR 2020
UL http://jcs.biologists.org/content/133/19/jcs235838.abstract
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.