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

doi:10.2147/DMSO.S296287

Insulin, but Not Metformin, Supports Wound Healing Process in Rats with Streptozotocin-Induced Diabetes

Diabetes Metab Syndr Obes. 2021 Apr 6:14:1505-1517. doi: 10.2147/DMSO.S296287. eCollection 2021.

Affiliations

¹ Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
² Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland.
³ Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
⁴ Nalecz Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warsaw, Poland.
⁵ Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.

Abstract

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.

Keywords: animal model; diabetes mellitus; neuropathy; ulceration.

Grants and funding

The study was funded by the statute fund of the Department of Diabetology and Internal Diseases of Medical University of Warsaw for 2016 and the Mini Student Grant of the Medical University of Warsaw for 2015/2016, number 1WO/NM1/2014.