A novel oral glucagon-like peptide 1 receptor agonist protects against diabetic cardiomyopathy via alleviating cardiac lipotoxicity induced mitochondria dysfunction

Abstract

Diabetic cardiomyopathy is one of the major cardiovascular complications of diabetes mellitus associated with left ventricular diastolic dysfunction. There are still no specific therapeutic guidelines for the disease. In recent years, glucagon-like peptide 1 receptor agonists were proved to exert cardioprotective effects in comprehensive studies. Therefore, we examined whether a novel oral availably glucagon-like peptide 1 receptor agonist, oral hypoglycemic peptide 2 (OHP2), could protect against diabetic cardiomyopathy in high-fat diets and continuous streptozocin injection induced rat models. After treatment for eight weeks, heart function was evaluated by echocardiography. As expected, OHP2 improved cardiac structure and function beyond glycemic control. Both hyperlipidemia and myocardium lipid accumulation were decreased by OHP2 treatment. In addition, OHP2 reversed oxidative stress and mitochondrial dysfunction in diabetic hearts. In vitro study suggested that OHP2 prevented palmitic acid-induced oxidative stress and mitochondrial dysfunction via suppressing intercellular lipid accumulation. Hence, our present findings pointed out that OHP2 is a promising oral glucagon-like peptide 1 receptor agonist for preventing diabetic cardiomyopathy.

Keywords: Diabetic cardiomyopathy; Lipotoxicity; Mitochondrial dysfunction; Oral GLP1RA; Oxidative stress.