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Effects of insulin on the skin: possible healing benefits for diabetic foot ulcers

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Abstract

Diabetic foot ulcers affect 15–20 % of all diabetic patients and remain an important challenge since the available therapies have limited efficacy and some of the novel therapeutic approaches, which include growth factors and stem cells, are highly expensive and their safety remains to be evaluated. Despite its low cost and safety, the interest for topical insulin as a healing agent has increased only in the last 20 years. The molecular mechanisms of insulin signaling and its metabolic effects have been well studied in its classical target tissues. However, little is known about the specific effects of insulin in healthy or even diabetic skin. In addition, the mechanisms involved in the effects of insulin on wound healing have been virtually unknown until about 10 years ago. This paper will review the most recent advances in the cellular and molecular mechanisms that underlie the beneficial effects of insulin on skin wound healing in diabetes. Emerging evidence that links dysfunction of key cellular organelles, namely the endoplasmic reticulum and the mitochondria, to changes in the autophagy response, as well as the impaired wound healing in diabetic patients will also be discussed along with the putative mechanisms whereby insulin could regulate/modulate these alterations.

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Acknowledgments

Authors thank Dr. M. Martins-Green, Dr. H. Jenssen and Dr. J. Moura Alves for a critical reading of the manuscript.

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Authors and Affiliations

  1. Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal

    T. Emanuelli, A. Burgeiro & E. Carvalho

  2. Department of Food Technology and Science, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil

    T. Emanuelli

  3. The Portuguese Diabetes Association (APDP), 1250-203, Lisbon, Portugal

    E. Carvalho

  4. Arkansas Children’s Research Institute, Little Rock, AR, 72202, USA

    E. Carvalho

  5. Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA

    E. Carvalho

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  1. T. Emanuelli
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This work was funded by FEDER (QREN), under projects CENTRO-07-ST24-FEDER-002002, CENTRO-07-ST24-FEDER-002006, CENTRO-07-ST24-FEDER-002008, Operational Programme Competitiveness Factors–COMPETE, by Foundation for Science and Technology EXCL/DTP-PIC/0069/2012 (EC), the EFSD European Research Programme in Microvascular Complications of Diabetes supported by Novartis (EC), and strategic project UID/NEU/04539/2013. T. Emanuelli is the recipient of CNPq-CSF Post doc Fellowship.

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Emanuelli, T., Burgeiro, A. & Carvalho, E. Effects of insulin on the skin: possible healing benefits for diabetic foot ulcers. Arch Dermatol Res 308, 677–694 (2016). https://doi.org/10.1007/s00403-016-1686-z

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