The Sodium-Glucose Co-Transporter 2 Inhibitor, Empagliflozin, Protects against Diabetic Cardiomyopathy by Inhibition of the Endoplasmic Reticulum Stress Pathway

Abstract

BACKGROUND/AIMS: This study aimed to determine whether or not the sodium-glucose co-transporter 2 inhibitor, empagliflozin (EMPA), can protect against diabetic cardiomyopathy (DCM) and to elucidate the related mechanism. METHODS: Rats were divided into the following four groups: a non-diabetic group; diabetic cardiomyopathy rats without EMPA treatment; and diabetic cardiomyopathy rats with EMPA treatment (low- and high-dose EMPA). Hemodynamic measurements were performed to evaluate left ventricular systolic and diastolic function. The histopathology of the heart was examined with hematoxylin-eosin staining. Expression of glucose-regulated protein (GRP)78, enhancer-binding protein homologous protein (CHOP), and caspase-12 was detected by Western blot, and the mRNA levels of XBP1, ATF4, and TRAF2 were analysed by real-time PCR. RESULTS: EMPA significantly decreased the blood glucose level when compared with vehicle. EMPA strongly improved cardiac function based on hemodynamic and histopathologic analyses. Moreover, EMPA can significantly down-regulate the expression of GRP78, CHOP, and caspase-12 (P < 0.01). Additionally, the mRNA levels of XBP1, ATF4, and TRAF2 were markedly decreased by administration of EMPA (P < 0.01). CONCLUSION: EMPA protects against DCM by inactivating the endoplasmic reticulum stress pathway.