Vargas-Vargas Manuel Alejandro, Saavedra-Molina Alfredo, Gómez-Barroso Mariana, Peña-Montes Donovan, Cortés-Rojo Christian, Rodríguez-Orozco Alain R, Rocío Montoya-Pérez
Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Francisco J. Múgica S/N, Col. Felicitas del Río, 58030, Morelia, Michoacán, México.
Facultad de Ciencias Médicas y Biológicas "Dr. Ignacio Chávez", Universidad Michoacana de San Nicolás de Hidalgo, Av. Dr. Rafael Carrillo S/N, Esq. Dr. Salvador González Herrejón Bosque, 58020, 58000, Cuauhtémoc, Morelia, Michoacán, México.
J Bioenerg Biomembr. 2023 Feb;55(1):71-78. doi: 10.1007/s10863-023-09958-7. Epub 2023 Feb 1.
AIM/INTRODUCTION: Diabetes Mellitus is a chronic degenerative disease, and its main biochemical characteristic is hyperglycemia due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Hyperglycemia causes dyslipidemia and stimulates oxidative damage, leading to the main symptoms, such as fatigue and culminates in diabetic complications. Previous studies have shown that ATP-sensitive potassium channels counteract muscle fatigue and metabolic stress in healthy mouse models. To determine the effect of diazoxide on muscle strength development during diabetes, we tested the effect of diazoxide in streptozotocin-diabetic rats in muscle function, lipid profile and oxidative stress biomarkers.
Wistar rats were divided into 4 groups of six animals each: (1) Control group, (2) diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). 4 weeks after rats were sacrificed, soleus and extensor digitorum longus muscles (EDL) were extracted to prepare homogenates and serum was obtained for biochemical measurements. Oxidative damage was evaluated by the thiobarbituric acid method and the fluorescent for reactive oxygen species (ROS) probe 2,4-HDCFDA, respectively.
Diabetic rats with diazoxide administration showed an increase in the development of muscle strength in both muscles; in turn, the onset of fatigue was longer compared to the group of diabetic rats without treatment. Regarding the lipid profile, diazoxide decreased total cholesterol levels in the group of diabetic rats treated with diazoxide (x̅46.2 mg/dL) compared to the untreated diabetic group (x̅=104.4 mg/dL); secondly, diazoxide decreased triglyceride concentrations (x̅=105.3 mg/dL) compared to the untreated diabetic rats (x̅=412.2 mg/dL) as well as the levels of very low-density lipoproteins (x̅=20.4 mg/dL vs. x̅=82.44 mg/dL). Regarding the various markers of oxidative stress, the diabetic group treated with diazoxide was able to reduce the concentrations of TBARS and total reactive oxygen species as well as preserve the concentrations of reduced glutathione.
Diazoxide administration in diabetic rats increases muscle strength development in EDL and soleus muscle, decreases fatigue, reduces cholesterol and triglyceride concentrations and improves oxidative stress parameters such as TBARS, ROS, and glutathione status.
目的/引言：糖尿病是一种慢性退行性疾病，其主要生化特征是由于胰岛素分泌受损、外周胰岛素作用抵抗或两者兼而有之导致的高血糖。高血糖会导致血脂异常并刺激氧化损伤，从而引发疲劳等主要症状，并最终导致糖尿病并发症。先前的研究表明，在健康小鼠模型中，ATP敏感性钾通道可对抗肌肉疲劳和代谢应激。为了确定二氮嗪对糖尿病期间肌肉力量发展的影响，我们测试了二氮嗪对链脲佐菌素诱导的糖尿病大鼠的肌肉功能、血脂谱和氧化应激生物标志物的影响。
将Wistar大鼠分为4组，每组6只动物：（1）对照组，（2）糖尿病组，（3）对照组+二氮嗪，（4）糖尿病+二氮嗪组（DB+DZX）。大鼠处死后4周，取出比目鱼肌和趾长伸肌（EDL）制备匀浆，并获取血清进行生化检测。分别通过硫代巴比妥酸法和活性氧（ROS）探针2,4 - HDCFDA荧光法评估氧化损伤。
给予二氮嗪的糖尿病大鼠在两块肌肉中的肌肉力量发展均有所增加；反过来，与未治疗的糖尿病大鼠组相比，疲劳发作时间更长。在血脂谱方面，与未治疗的糖尿病组（x̅ = 104.4mg/dL）相比，给予二氮嗪治疗的糖尿病大鼠组中二氮嗪降低了总胆固醇水平（x̅ = 46.2mg/dL）；其次，与未治疗的糖尿病大鼠（x̅ = 412.2mg/dL）相比，二氮嗪降低了甘油三酯浓度（x̅ = 105.3mg/dL）以及极低密度脂蛋白水平（x̅ = 20.4mg/dL对x̅ = 82.44mg/dL）。在各种氧化应激标志物方面，给予二氮嗪治疗的糖尿病组能够降低丙二醛和总活性氧的浓度，并维持还原型谷胱甘肽的浓度。
给糖尿病大鼠施用二氮嗪可增加EDL和比目鱼肌的肌肉力量发展，减少疲劳，降低胆固醇和甘油三酯浓度，并改善氧化应激参数，如丙二醛、活性氧和谷胱甘肽状态。
