Effects of Exendin-4 on diabetic wounds: Direct action on proliferative phase of wound healing

Abstract: Background: Impaired wound healing is one of the most well-known complications of type 2 diabetes mellitus. Experimental evidence suggested that treatment with Exendin-4, a glucagon-like peptide-1 agonist displaying a wide range of antidiabetic effects, can promote tissue regeneration. Objectives: Thus, this study aimed to examine the efficacy of topical treatment with Exendin-4 in accelerating wound healing in normoglycemic and hyperglycemic mice. Methods: For this purpose, two wounds inflicted on the back skin of 12 normo- and 12 hyperglycemic mice were injected intradermally with either saline solution or Exendin-4. Wounds were collected at the time of abrasion (T0), 48 h (T1), 96 h (T2), and 144 h (T3) and cryosections were analyzed by histological and histochemical methods. Results: In wounds treated with Exendin-4, an 85% reduction in size was observed at T3, and the thickness of the epidermis was statistically lower than in untreated wounds. The significative difference was observed in Exendin-4 treated wounds at T2 and T3 in the infiltration of granulocyte populations and at T3 in the degranulation index by mast cells and in the increase in vessels. Fibroblasts were significantly increased in Exendin-4 treated wounds of normo- and hyperglycemic mice at T3, which began to differentiate into myofibroblasts, from T2, and at T3 reached significant values. Conclusion: Taken all together, these results indicate that the topical administration of Exendin-4 had beneficial effects on the acceleration of the healing process of skin wounds in both normo- and hyperglycemic mice.