Autophagy promotion and fibrosis inhibition by combination of GLP1 analogue and metformin decreasing the progression of type II diabetic cardiomyopathy of albino rats: Immunohistochemical study

Abstract

Diabetic cardiomyopathy is one of the most serious chronic complications of type 2 diabetes. This study aimed to examine the therapeutic effect of GLP1 and metformin combination as oral antidiabetic drugs on diabetic cardiomyopathy through promotion of oxidative stress, improvement of autophagy of the cardiomyocytes and regression of cardiac fibrosis. Type 2 diabetes mellitus was induced by feeding the rats high fat diet for 12 week then injecting streptozotocin (30mg/kg) intraperitoneally after 4 weeks. One group of diabetic rats received metformin (30mg/kg), another group of diabetic rats received GLP1 analogue; liraglutide (75 μg/kg) and the last group of diabetic rats received combination of both drugs. After 24 hours of the experiment, the cardiac tissues were fixed in formalin and embedded in paraffin blocks to be examined histopathologically and immunohistochemically for autophogic markers (LC3 and P62). Also homogenate of heart tissues was made to measure oxidative stress markers (MDA, GSH) in the supernatant. Light microscope examination showed typical features of diabetic cardiomyopathy in diabetic group with increase in fibrous tissue interstitially and around blood vessels, which markedly improved in diabetic rats which received combination of both drugs, also combination of both drugs showed significant increase in early and late markers autophagy LC3 and P62 respectively when compared with diabetic rats, finally synergetic effect of both drug markedly improved oxidative stress (MDA,GSH activity). So we think that our study is the first study that discuss the therapeutic effect of combination of GLP1 analogue and metformin on diabetic cardiomyopathy through the antioxidative stress, antifibrotic and autophagic improving