title: Effects of insulin on the skin: possible healing benefits for diabetic foot ulcers.
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.
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal.|Department of Food Technology and Science, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Emanuelli
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Burgeiro
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal. ecarvalh@cnc.uc.pt.|The Portuguese Diabetes Association (APDP), 1250-203, Lisbon, Portugal. ecarvalh@cnc.uc.pt.|Arkansas Children's Research Institute, Little Rock, AR, 72202, USA. ecarvalh@cnc.uc.pt.|Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA. ecarvalh@cnc.uc.pt.
authors.forename: E
authors.initials: E
authors.lastname: Carvalho
mesh_terms: D000279:Administration, Cutaneous; D017719:Diabetic Foot / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011972:Receptor, Insulin; D020782:Matrix Metalloproteinases
keywords: Angiogenesis; Diabetes; Inflammatory response; Insulin; Skin cells; Wound healing