Glucose Transporter 4 and Peroxisome Proliferator-Activated Receptor-Alpha Overexpression Association With Cardioprotective Effects of Myoinositol and Metformin Combination in Type 2 Diabetic Rat Model

Background: Type 2 diabetes mellitus (DM) has many complications associated with increased morbidity and mortality. Cardiovascular complications are one of these serious complications. Therefore, there is a need for early and effective management to hamper them. This study aimed to evaluate the cardioprotective efficacy of metformin and myoinositol combination through exploring the associated underlying mechanisms in type 2 DM rat model. Methods: Type 2 DM model was induced in rats by streptozotocin and high-fat diet. Rats were treated with metformin (150 mg/kg) and/or myoinositol (50 mg/kg) by oral gavage once daily for 4 weeks. Immunohistochemistry was used to assess the drugs’ cardioprotective efficacy by estimating troponin T, nuclear factor kappa B (NF-kappaB) and tumor necrosis factor alpha (TNF-alpha). Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to investigate peroxisome proliferator-activated receptor-alpha (PPARalpha) and glucose transporter 4 (GLUT-4) expression levels in the skeletal muscles, respectively. Results: This study found that metformin and myoinositol combination was associated with GLUT-4 and PPARalpha overexpression, together with better lipid profile than metformin alone in diabetic rats. Additionally, the combination of both drugs improved troponin C and decreased creatine kinase MB isoenzyme, NF-kappaB and TNF-alpha cardiac levels. Conclusion: The current study indicated that myoinositol in combination with metformin had better cardioprotective effect than metformin alone in type 2 DM. This favorable effect was exhibited through upregulation of GLUT-4 and PPARalpha receptors expression in skeletal muscles, thus increasing insulin sensitivity and improving lipid profile. J Endocrinol Metab. 2021;11(5):140-151 doi: https://doi.org/10.14740/jem765