Handling Editor: Daniel Billadeau
ABSTRACT
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: P.Y., X.Z., Y.L.; Methodology: X.W., D.W.; Software: M.Z., T.Y.; Formal analysis: Y.S.; Investigation: P.Y., X.W., D.W., D.L., M.G., Y.L.; Resources: T.Y.; Data curation: P.Y., Y.S., D.L.; Writing - original draft: P.Y.; Writing - review & editing: X.Z.; Visualization: M.Z.; Supervision: Y.L.; Project administration: X.Z., Y.L.; Funding acquisition: X.Z., Y.L.
Funding
This study is supported by the National Natural Science Foundation of China (81170761, 81270909, 81671914), Shanghai Hospital Development Center (SHDC12014117), Shanghai Municipal Key Clinical Specialty (shslczdzk02302), Shanghai Chinese and Western Medicine Clinical Cooperation Pilot Cultivation Project [ZY(2018-2020)-FWTX-1106], Ruijin Youth NSFC Cultivation Fund (2019QNPY01003) and Shanghai Jiao Tong University Medical Engineering Cross Research Funds (YG2019QNA35).
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.235838.supplemental
- Received July 5, 2019.
- Accepted August 24, 2020.
- © 2020. Published by The Company of Biologists Ltd
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