The Role of Metformin and Aerobic Exercise on The Hepatic Ischemia-Reperfusion Injury in Streptozotocin-Induced Diabetic Mice

Abstract

Due to prolonged hyperglycemia many of the diabetic patients suffer from complications such as liver damage. Diabetic patients are known to have the need for liver surgeries more than non-diabetic do. The ischemia reperfusion injuries (IRI) are one of the main complications of these surgeries and the IRI-related increase in oxidative stress has been known to be higher in diabetic patients. Metformin and aerobic exercise are important tools being used especially in type-2 diabetes. However, their effects and roles in liver IRI in type-1 diabetic patients are not known. This study aimed to investigate the effects of metformin and exercise on hepatic IRI in diabetes in streptozotocin induced type-1 diabetic mice. Diabetes was induced by streptozotocin and two weeks after the disease developed, mice were started to treat with metformin and/or aerobic exercise during four-weeks. Blood glucose levels of the mice were measured again and the glucose tolerance test (OGTT) was performed for each mouse. The day after OGTT, ischemia was performed for 45 minutes in the liver and then reperfusion was provided for 5 hours. The liver of the mice was isolated at the end of the experiments. The malondialdehyde, superoxide dismutase and nitrite levels were measured with colorimetric analysis. Metformin reduced the insulin resistance alone and together with aerobic exercise. Oxidative stress in the liver after IRI was diminished both with metformin and/or aerobic exercise in diabetic mice. Our study indicated that metformin accompanied with aerobic exercise might be an important treatment strategy for preventing the IRI in the liver of type-1 diabetic patients.