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Research Article
Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization
Peilang Yang, Xiqiao Wang, Di Wang, Yan Shi, Meng Zhang, Tianyi Yu, Dan Liu, Min Gao, Xiong Zhang, Yan Liu
Journal of Cell Science 2020 133: jcs235838 doi: 10.1242/jcs.235838 Published 12 October 2020
Peilang Yang
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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  • ORCID record for Peilang Yang
Xiqiao Wang
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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Di Wang
2Department of Anesthesiology, Shanghai No. 6 People's Hospital, Shanghai 200233, China
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Yan Shi
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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Meng Zhang
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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Tianyi Yu
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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Dan Liu
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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Min Gao
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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Xiong Zhang
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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  • For correspondence: rjliuyan@126.com xiong@medmail.com.cn
Yan Liu
1Department of Burns and Plastic Surgery, Shanghai Jiao Tong University, School of Medicine, Ruijin Hospital, Shanghai 200025, China
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  • For correspondence: rjliuyan@126.com xiong@medmail.com.cn

Handling Editor: Daniel Billadeau

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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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Keywords

  • Diabetes
  • Wound healing
  • Insulin
  • Macrophages
  • Neutrophils

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Research Article
Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization
Peilang Yang, Xiqiao Wang, Di Wang, Yan Shi, Meng Zhang, Tianyi Yu, Dan Liu, Min Gao, Xiong Zhang, Yan Liu
Journal of Cell Science 2020 133: jcs235838 doi: 10.1242/jcs.235838 Published 12 October 2020
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Research Article
Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization
Peilang Yang, Xiqiao Wang, Di Wang, Yan Shi, Meng Zhang, Tianyi Yu, Dan Liu, Min Gao, Xiong Zhang, Yan Liu
Journal of Cell Science 2020 133: jcs235838 doi: 10.1242/jcs.235838 Published 12 October 2020

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