Background: Endogenous hydrogen sulfide (H₂S) is emerging as a key signal molecule in the development of diabetic cardiomyopathy. The aim of this study was to explore the effect and underlying mechanism of S-propargyl-cysteine (SPRC), a novel modulator of endogenous H₂S, on diabetic cardiomyopathy in db/db diabetic mice.

Methods and Results: Vehicle or SPRC were orally administered to 8-month-old male db/db mice and their wild type littermate for 12 weeks. SPRC treatment ameliorated myocardial hypertrophy, fibrosis, and cardiac systolic dysfunction assessed by histopathological examinations and echocardiography. The functional improvement by SPRC was accompanied by a reduction in myocardial lipid accumulation and ameliorated plasma lipid profiles. SPRC treatment improved glucose tolerance in db/db mice, with fasting blood glucose and peripheral insulin resistance remaining unchanged. Furthermore, insulin receptor signaling involving the phosphorylation of protein kinase B (Akt/PKB) and glycogen synthase kinase 3β (GSK3β) were elevated and activated by SPRC treatment. Primary neonatal mice cardiomyocytes were cultured to explore the mechanisms of SPRC on diabetic cardiomyopathy in vitro. Consistent with the results in vivo, SPRC not only up-regulated insulin receptor signaling pathway in cardiomyocytes in dose-dependent manner in the basal state, but also relieved the suppression of insulin receptor signaling induced by high concentrations of glucose and insulin. Furthermore, SPRC also enhanced the expression of glucose transporter 4 (GLUT4) and ³H glucose uptake in cardiomyocytes.

Conclusions: In this study, we found a novel beneficial effect of SPRC on diabetic cardiomyopathy, which was associated with activation of insulin receptor signaling. SPRC may be a promising medication for diabetic cardiomyopathy in type 2 diabetes mellitus patients.

背景：内源性硫化氢 (H ₂ S) 正在成为糖尿病心肌病发展中的关键信号分子。本研究的目的是探讨内源性 H ₂ S的新型调节剂 S-炔丙基-半胱氨酸 (SPRC)对糖尿病心肌病的影响和潜在机制。分贝/分贝 糖尿病小鼠。

方法和结果： 载体或 SPRC 口服给药于 8 个月大的男性 分贝/分贝小鼠及其野生型同窝仔 12 周。SPRC 治疗改善了通过组织病理学检查和超声心动图评估的心肌肥大、纤维化和心脏收缩功能障碍。SPRC 的功能改善伴随着心肌脂质积累的减少和血浆脂质谱的改善。SPRC 治疗改善了糖耐量分贝/分贝空腹血糖和外周胰岛素抵抗保持不变。此外，涉及蛋白激酶 B (Akt/PKB) 和糖原合酶激酶 3β (GSK3β) 磷酸化的胰岛素受体信号被 SPRC 治疗提升和激活。原代新生小鼠心肌细胞培养探讨SPRC对糖尿病心肌病的作用机制体外. 与结果一致体内，SPRC不仅在基础状态以剂量依赖性方式上调心肌细胞中的胰岛素受体信号通路，而且还解除了高浓度葡萄糖和胰岛素诱导的胰岛素受体信号传导的抑制。此外，SPRC 还增强了心肌细胞中葡萄糖转运蛋白 4 (GLUT4) 的表达和³ H 葡萄糖摄取。

结论：在这项研究中，我们发现了 SPRC 对糖尿病心肌病的一种新的有益作用，这与胰岛素受体信号传导的激活有关。SPRC 可能是治疗 2 型糖尿病患者糖尿病心肌病的一种有前途的药物。