Golpasandi Hadi, Rahimi Mohammad Rahman
Department of Exercise Physiology, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Iran.
Cardiovasc Ther. 2025 Mar 19;2025:8817195. doi: 10.1155/cdr/8817195. eCollection 2025.
This study investigated the effect of vitamin D3 injection combined with high-intensity interval training on cell signaling pathways involved in excessive autophagy, specifically the mTOR (mechanistic target of rapamycin)-Beclin-1-Fyco-1 (FYVE and coiled-coil domain-containing protein 1)-cathepsin D pathway, in the heart tissue of Type 2 diabetes-induced rats. In this experimental study, 32 male Wistar rats were fed a high-fat diet for 6 weeks to induce Type 2 diabetes, followed by a single subcutaneous injection of 35 mg/kg streptozotocin (STZ). The rats were then randomly assigned to one of four groups: (1) diabetes control (DC), (2) diabetes + HIIT (DT), (3) diabetes + vitamin D3 (DV), and (4) diabetes + HIIT + vitamin D3 (DTV). HIIT sessions were conducted for 8 weeks, five times per week, at an intensity of 85%-95% of maximum running speed ( ), while vitamin D3 was administered weekly via subcutaneous injection at a dose of 10,000 IU/kg. Twenty-four hours after the intervention period, heart and left ventricular tissues were collected for analysis of the levels of autophagy signaling proteins mTOR, phosphorylated mechanistic target of rapamycin (pmTOR), Beclin-1, Fyco-1, and cathepsin D. Two-way ANOVA revealed that Type 2 diabetes significantly increased the levels of Beclin-1, Fyco-1, and cathepsin D ( < 0.001) while significantly reducing the levels of mTOR and pmTOR ( < 0.001). HIIT, vitamin D3 injection, and their combined treatment significantly decreased the levels of Beclin-1, Fyco-1, and cathepsin D and increased the levels of mTOR and pmTOR compared to the diabetes control group ( < 0.001). Type 2 diabetes increases autophagy in the left ventricle, marked by altered levels of key autophagy proteins. HIIT and vitamin D3 injections mitigate these effects by enhancing mTOR signaling and reducing excessive autophagy. These interventions show promise as nonpharmacological strategies to improve cardiac health in Type 2 diabetes and could be incorporated into clinical and rehabilitation programs.
本研究调查了维生素D3注射联合高强度间歇训练对2型糖尿病诱导大鼠心脏组织中与过度自噬相关的细胞信号通路的影响，具体为mTOR（雷帕霉素作用靶点）-Beclin-1-Fyco-1（含FYVE和卷曲螺旋结构域蛋白1）-组织蛋白酶D通路。在这项实验研究中，32只雄性Wistar大鼠喂食高脂饮食6周以诱导2型糖尿病，随后单次皮下注射35mg/kg链脲佐菌素（STZ）。然后将大鼠随机分为四组之一：（1）糖尿病对照组（DC），（2）糖尿病+高强度间歇训练组（DT），（3）糖尿病+维生素D3组（DV），和（4）糖尿病+高强度间歇训练+维生素D3组（DTV）。高强度间歇训练 sessions 进行8周，每周5次，强度为最大跑步速度的85%-95%（），而维生素D3每周通过皮下注射给药，剂量为10,000IU/kg。干预期结束24小时后，收集心脏和左心室组织，分析自噬信号蛋白mTOR、磷酸化雷帕霉素作用靶点（pmTOR）、Beclin-1、Fyco-1和组织蛋白酶D的水平。双向方差分析显示，2型糖尿病显著增加了Beclin-1、Fyco-1和组织蛋白酶D的水平（<0.001），同时显著降低了mTOR和pmTOR的水平（<0.001）。与糖尿病对照组相比，高强度间歇训练、维生素D3注射及其联合治疗显著降低了Beclin-1、Fyco-1和组织蛋白酶D的水平，并增加了mTOR和pmTOR的水平（<0.001）。2型糖尿病增加左心室自噬，以关键自噬蛋白水平改变为特征。高强度间歇训练和维生素D3注射通过增强mTOR信号传导和减少过度自噬来减轻这些影响。这些干预措施有望作为改善2型糖尿病心脏健康的非药物策略，并可纳入临床和康复计划。
