Insulin, but Not Metformin, Supports Wound Healing Process in Rats with Streptozotocin-Induced Diabetes.
Mateusz Mieczkowski, Beata Mrozikiewicz-Rakowska, Tomasz Siwko, Magdalena Bujalska-Zadrozny, Anna de Corde-Skurska, Renata Wolinska, Emilia Gasinska, Tomasz Grzela, Piotr Foltynski, Michal Kowara, Zofia Mieczkowska, Leszek Czupryniak
Author Information
Mateusz Mieczkowski: Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. ORCID
Beata Mrozikiewicz-Rakowska: Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. ORCID
Tomasz Siwko: Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
Magdalena Bujalska-Zadrozny: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland. ORCID
Anna de Corde-Skurska: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland.
Renata Wolinska: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland. ORCID
Emilia Gasinska: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland.
Tomasz Grzela: Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland. ORCID
Piotr Foltynski: Nalecz Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warsaw, Poland. ORCID
Michal Kowara: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. ORCID
Zofia Mieczkowska: Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
Leszek Czupryniak: Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. ORCID
PURPOSE: Optimal glycemic control is crucial for proper wound healing in patients with diabetes. However, it is not clear whether other antidiabetic drugs support wound healing in mechanisms different from the normalization of blood glucose control. We assessed the effect of insulin and metformin administration on the wound healing process in rats with streptozotocin-induced diabetes. METHODS: The study was conducted on 200 male Wistar rats with streptozotocin-induced diabetes. In the last phase of the study, 45 rats, with the most stable glucose levels in the range of 350-500 mg/dL, were divided into three groups: group I received human non-protamine insulin subcutaneously (5 IU/kg body mass) once a day, group II received metformin intragastrically (500 mg/kg b.m.), and group III (control) was given saline subcutaneously. After 14 days of antidiabetic treatment, a 2 cm × 2 cm thin layer of skin was cut from each rat's dorsum and a 4 cm disk with a hole in its center was sewn in to stabilize the skin and standardize the healing process. The wound healing process was followed up for 9 days, with assessment every 3 days. Biopsy samples were subjected to hematoxylin and eosin staining and immunohistochemical assays. RESULTS: Analysis of variance revealed significant influence of treatment type (insulin, control, or metformin) on the relative change in wound surface area. The wound healing process in rats treated with insulin was more effective than in the metformin and control groups. Wound tissue samples taken from the insulin-treated animals presented significantly lower levels of inflammatory infiltration. Immunohistochemical assessment showed the greatest density of centers of proliferation Ki-67 in insulin-treated animals. CONCLUSION: These results suggest that an insulin-based treatment is more beneficial than metformin, in terms of accelerating the wound healing process in an animal model of streptozocin-induced diabetes.
