Abstract
Type 2 Diabetes Mellitus patients are predisposed to serious cardiovascular morbidity and mortality. Diabetes causes different structural and functional alterations in the myocardial tissue, which are induced by hyperglycemia, insulin resistance, and hyperlipidemia. The resulting cardiomyopathy is characterized by myocardial fibrosis, dysfunctional remodeling and eventually, clinical heart failure. This study addressed the effects of resveratrol and pioglitazone to ameliorate diabetic cardiovascular complications using a db/db diabetic mice model. Male db/db diabetic mice were randomly assigned to orally receive resveratrol (50 mg/kg, n=5), resveratrol/pioglitazone (50 mg/kg and 20 mg/day, respectively, n=5) for the space of 6 weeks. Non-diabetic lean mice (n=5) were included as a control group. Histopathological analyses were performed in heart and aortic vessel tissue samples using hematoxylin and eosin, as well as Masson Trichromic staining. VCAM-1 immunohistochemistry was also assessed. Blood glucose, hemoglobin A1c, insulin, glycosuria, triglycerides, cholesterol, and LDL cholesterol were all examined. Present data suggest that the combination of pioglitazone plus resveratrol significantly lower circulating levels of insulin, hemoglobin A1c, glucose, triglycerides, cholesterol, and LDL levels. Our results also show that tissue damage to the heart and aortic vessels caused by diabetes can also be improved by the administration of said combination. The present study demonstrates that resveratrol/pioglitazone combination therapy improves carbohydrate and lipid metabolism, as well as improving diabetic cardiomyopathy in diabetic mice by producing a synergistic pharmacological effect. The combination of resveratrol plus pioglitazone has therapeutic potential against diabetic cardiomyopathy.
Highlights
Patients suffering from Type 2 Diabetes Mellitus (DM) are more prone to develop cardiovascular complications [1]
Cardiac insulin resistance is characterized by a cellular and tissue reorganization leading to cardiomyopathy, cardiac fibrosis and impaired molecular signaling, which in turn cause the death of myocytes and endothelial cells [4]
This study addressed the effects of resveratrol, alone or combined with conventional pioglitazone, on cardiovascular complications induced by diabetes using a db/db diabetic mice model
Summary
Patients suffering from Type 2 Diabetes Mellitus (DM) are more prone to develop cardiovascular complications [1]. The cardiovascular adaptations present in Type 2 DM (i.e. atherosclerosis, hypertension, ischemic disease, stroke, etc.) are associated with diverse molecular and cellular responses mainly derived from insulin resistance, an excess of free fatty acids, hyperglycemia, inflammation, thrombosis, and hypertension [2,3]. Current pharmacological therapies for diabetic cardiomyopathy are focused on regulating the glucose metabolism, oxidative damage, calcium handling, carbohydrate utilization in cardiomyocytes, and the preservation of the myocardium’s structure and function [7-13]. Pioglitazone is a glucose-lowering agent that protects against cardiovascular disease associated with Type 2 DM. Pioglitazone reduces the most important cardiovascular events in Type 2 DM patients because it improves cardiac insulin resistance, carbohydrate and lipid metabolism, and reduces inflammation [14,15]
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