Neuregulin-4 intervention significantly alleviated myocardial injury and improved cardiac function by promoting autophagy via the AMPK/mTOR signalling pathway in type 1 diabetic mice.
Does Neuregulin-4 attenuate diabetic cardiomyopathy in type 1 diabetic mice?
Neuregulin-4 attenuates diabetic cardiomyopathy in preclinical models by promoting autophagy via the AMPK/mTOR signaling pathway, suggesting a potential future therapeutic target.
p-value: p=<0.05
BACKGROUND: Diabetic cardiomyopathy is characterized by left ventricle dysfunction, cardiomyocyte apoptosis, and interstitial fibrosis and is a serious complication of diabetes mellitus (DM). Autophagy is a mechanism that is essential for maintaining normal heart morphology and function, and its dysregulation can produce pathological effects on diabetic hearts. Neuregulin-4 (Nrg4) is an adipokine that exerts protective effects against metabolic disorders and insulin resistance. The aim of this study was to explore whether Nrg4 could ameliorate DM-induced myocardial injury by regulating autophagy. METHODS: Four weeks after the establishment of a model of type 1 diabetes in mice, the mice received Nrg4 treatment (with or without an autophagy inhibitor) for another 4 weeks. The cardiac functions, histological structures and cardiomyocyte apoptosis were investigated. Autophagy-related protein levels along with related signalling pathways that regulate autophagy were evaluated. In addition, the effects of Nrg4 on autophagy were also determined in cultured primary cardiomyocytes. RESULTS: Nrg4 alleviated myocardial injury both in vivo and in vitro. The autophagy level was decreased in type 1 diabetic mice, and Nrg4 intervention reactivated autophagy. Furthermore, Nrg4 intervention was found to activate autophagy via the AMPK/mTOR signalling pathway. Moreover, when autophagy was suppressed or the AMPK/mTOR pathway was inhibited, the beneficial effects of Nrg4 were diminished. CONCLUSION: Nrg4 intervention attenuated diabetic cardiomyopathy by promoting autophagy in type 1 diabetic mice. Additionally, Nrg4 induced autophagy via the AMPK/mTOR signalling pathway.
Wang et al. (Tue,) conducted a other in Diabetic cardiomyopathy (n=48). Neuregulin-4 (Nrg4) vs. Vehicle (PBS) was evaluated on Myocardial injury, cardiac function (LVEF, LVFS), and autophagy levels (p=<0.05). Neuregulin-4 intervention significantly alleviated myocardial injury and improved cardiac function by promoting autophagy via the AMPK/mTOR signalling pathway in type 1 diabetic mice.