Anti-inflammatory, procollagen, and wound repair properties of topical insulin gel

Abstract

Diabetes mellitus is associated with impaired wound healing. The topical use of insulin is a promising therapy because it may favor all phases of the wound healing process. This study aimed to investigate the therapeutic outcomes of insulin gel in wounds of hyperglycemic mice. After diabetes induction, a 1-cm 2 full-thickness wound was created on each animal's dorsum. The lesions were treated daily for 14 days with insulin gel (insulin group) or vehicle gel without insulin (vehicle group). Tissue samples were extracted on days 4, 7, 10, and 14 after the creation of the lesion. The samples were analyzed with hematoxylin/eosin and Sirius red staining, immunohistochemistry, Bio-Plex immunoassays, and western blotting. Insulin gel favored re-epithelialization at day 10 and increased the organization and deposition of collagen. Additionally, it modulated the expression of cytokines (interleukin (IL)-4 and IL-10) and increased the expression of arginase I, VEGF receptor 1, and VEGF on day 10. Activation of the insulin signaling pathway occurred via IRβ, IRS1, and IKK on day 10 and activation of Akt and IRS1 on day 14. These results suggested that insulin gel improved wound healing in hyperglycemic mice by modulating the expression of inflammatory factors, growth factors, and proteins of the insulin signaling pathway.

In Vitro and In Vivo Evaluation of Chitosan/HPMC/Insulin Hydrogel for Wound Healing Applications

“…Insulin is a peptide hormone which exerts functions in different types of body tissue, including the skin. Other studies that investigate topical insulin for wound healing showed it modulates the re-epithelialization process, stimulating cell proliferation and migration of keratinocytes [13,49]. Biodegradable carbohydrate polymers control hydrogel degradation while liberating the hormone in a continued manner [9].…”

“…The systemic effects of topical insulin can be influenced by its concentration [54]. However, the use of this dose in the study is justifiable because insulin gel enhances wound healing without alterations in glucose level [49].…”

“…Insulin use for the treatment of non-healing wounds is widespread in the literature [4,6,9,13,30,49,51,[53][54][55][56][62][63][64][65][66][67][68][69][70][71]. Some studies have elucidated the effects of insulin creams, hydrogels, or solutions in the wound-healing process [6,13,54,70].…”

“…Although the application of topical insulin as a wound dressing has been investigated using different types of formulations, such as hydrogels, creams, and fibers [9,49,51,55], there is no consensus regarding the dosage of insulin necessary to promote wound healing. These data can vary in the literature in terms of application frequency and the amount of insulin that each product has.…”

Metabolic reprogramming in skin wound healing

“…In terms of glucose metabolism, Apolinário et al . [ 106 ] revealed that the topical use of insulin may improve skin wound healing in hyperglycaemic mice by modulating the expression of inflammatory factors, growth factors, and proteins in the insulin signalling pathway. Yang et al .…”