Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Pharmacology & Toxicology Department, Qunfudah Medical Collage, Umm Al-Qura University, Saudi Arabia.
Biomed Pharmacother. 2022 Sep;153:113382. doi: 10.1016/j.biopha.2022.113382. Epub 2022 Jul 13.
Diabetic cardiomyopathy (DCM) is linked to disturbance in cardiac glucose handling and increased cardiac glycogen storage. This study tested the potential role of sacubitril/valsartan on the progression of DCM in high fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic rats compared to valsartan alone, including their effects on the cardiac glycophagy process.
Rats were fed on HFD for 6 weeks followed by single low-dose STZ (35 mg/kg). After confirming hyperglycemia, diabetic rats were continued on HFD and divided into three subgroups: Untreated-diabetic, Valsartan-treated diabetic and Sacubitril/valsartan-treated diabetic groups; in addition to a control group. Changes in ECG, blood glucose, serum insulin, lipid profile, and Homeostasis model of assessment of insulin resistance (HOMA-IR) were assessed and the degree of cardiac fibrosis was examined. Cardiac glycogen content and glycophagy process were evaluated.
Sacubitril/valsartan administration to diabetic rats resulted in improvement of metabolic changes more than valsartan alone. Also, sacubitril/valsartan effectively prevented diabetes-associated cardiac hypertrophy, QTc prolongation, and fibrosis. Finally, cardiac glycogen concentrations in diabetic rats were decreased by sacubitril/valsartan combination, coupled with significant induction of glycophagy process in the diabetic rats' heart.
Sacubitril/valsartan therapy provides a more favorable metabolic and cardioprotective response compared to valsartan alone in a rat model of DCM. These findings may be due to a direct cardioprotective impact of sacubitril/valsartan and secondary beneficial effects of improved hyperglycemia and dyslipidemia. In addition, these beneficial cardiac effects could be attributed to the induction of the glycophagy process and alleviating cardiac glycogen overload.
糖尿病心肌病（DCM）与心脏葡萄糖处理紊乱和心脏糖原储存增加有关。本研究测试了沙库巴曲缬沙坦与缬沙坦单药治疗相比，在高脂肪饮食（HFD）/链脲佐菌素（STZ）诱导的 2 型糖尿病大鼠 DCM 进展中的潜在作用，包括对心脏糖异生过程的影响。
大鼠先接受 HFD 喂养 6 周，然后给予单次低剂量 STZ（35mg/kg）。确认高血糖后，糖尿病大鼠继续接受 HFD 喂养，并分为三组：未治疗的糖尿病组、缬沙坦治疗的糖尿病组和沙库巴曲缬沙坦治疗的糖尿病组；此外还有一个对照组。评估心电图、血糖、血清胰岛素、血脂谱和胰岛素抵抗评估的稳态模型（HOMA-IR），并检查心肌纤维化程度。评估心脏糖原含量和糖异生过程。
与缬沙坦单药治疗相比，沙库巴曲缬沙坦给药可改善代谢变化。此外，沙库巴曲缬沙坦可有效预防糖尿病相关的心肌肥大、QTc 延长和纤维化。最后，沙库巴曲缬沙坦联合用药可降低糖尿病大鼠心脏的糖原浓度，并显著诱导糖尿病大鼠心脏的糖异生过程。
与缬沙坦单药治疗相比，沙库巴曲缬沙坦治疗在 DCM 大鼠模型中提供了更有利的代谢和心脏保护反应。这些发现可能是由于沙库巴曲缬沙坦的直接心脏保护作用以及改善高血糖和血脂异常的继发有益影响。此外，这些有益的心脏作用可能归因于诱导糖异生过程和减轻心脏糖原过载。
