Carvacrol Attenuates Diabetic Cardiomyopathy by Modulating the PI3K/AKT/GLUT4 Pathway in Diabetic Mice

作者：Ning Hou, Yun-Pei Mai, Xiaoxia Qiu, Wenchang Yuan, Yilang Li, Cheng-Feng Luo, Yun Liu, Guiping Zhang, Ganjiang Zhao, Jiandong Luo · 发表于：Frontiers in Pharmacology · 年份：2019 · DOI：10.3389/fphar.2019.00998 · 被引用次数：92 · 研究领域：Metabolism, Diabetes, and Cancer、Cardiovascular Function and Risk Factors、Pharmacology and Obesity Treatment

Background: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus, eventually leads to heart failure. Carvacrol is a food additive with diverse bioactivities. We aimed to study the protective effects and mechanisms of carvacrol in DCM. Methods: We used a streptozotocin-induced and db/db mouse model of types 1 and 2 diabetes mellitus (T1DM and T2DM), respectively. Both study groups received daily intraperitoneal injections of carvacrol for 6 weeks. Cardiac remodeling was evaluated by histological analysis. We determined gene expression of cardiac remodeling markers (Nppa and Myh7) by quantitative real-time PCR and cardiac function by echocardiography. Changes of PI3K/AKT signaling were determined with Western blotting. GLUT4 translocation was evaluated by Western blotting and immunofluorescence staining. Results: Compared with control mice, both T1DM and T2DM mice showed cardiac remodeling and left ventricular dysfunction. Carvacrol significantly reduced blood glucose levels and suppressed cardiac remodeling in mice with T1DM and T2DM. At the end of the treatment period, both T1DM and T2DM mice showed lesser cardiac hypertrophy, Nppa and Myh7 mRNA expression, and cardiac fibrosis, compared to mice administered only the vehicle. Moreover, carvacrol significantly restored PI3K/AKT signaling, which was impaired in mice with T1DM and T2DM. Carvacrol increased levels of phosphorylated PI3K, PDK1, AKT, and AS160, and inhibited PTEN phosphorylation in mice with T1...