Diazoxide improves muscle function in association with improved dyslipidemia and decreased muscle oxidative stress in streptozotocin-induced diabetic rats

by Selleckchem | Sep 27 2023

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.

Materials and methods: 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-H2DCFDA, respectively.

Results: 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.

Conclusion: 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.

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Introduction: Diabetes Mellitus is a chronic degenerative disease characterized by hyperglycemia, which results from impaired insulin secretion, peripheral insulin resistance, or both. Hyperglycemia leads to dyslipidemia and oxidative damage, resulting in symptoms such as fatigue and eventually leading to diabetic complications. Previous studies have shown that ATP-sensitive potassium channels play a role in counteracting muscle fatigue and metabolic stress in healthy mouse models. In this study, we aimed to determine the effect of diazoxide, an ATP-sensitive potassium channel opener, on muscle strength development in diabetic rats, as well as its impact on lipid profile and oxidative stress biomarkers.

Materials and Methods: Wistar rats were divided into four groups: (1) Control group, (2) Diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). Each group consisted of six animals. After four weeks, the rats were sacrificed, and their soleus and extensor digitorum longus (EDL) muscles were extracted for homogenization. Serum was obtained for biochemical measurements. Oxidative damage was assessed using the thiobarbituric acid method and the fluorescent probe 2,4-H2DCFDA to measure reactive oxygen species (ROS).

Results: The diabetic rats treated with diazoxide showed an increase in muscle strength development in both the soleus and EDL muscles. Additionally, the onset of fatigue was delayed compared to the diabetic rats without treatment. In terms of lipid profile, diazoxide administration in the diabetic group resulted in decreased total cholesterol levels (average: 46.2 mg/dL) compared to the untreated diabetic group (average: 104.4 mg/dL). Similarly, diazoxide reduced triglyceride concentrations (average: 105.3 mg/dL) compared to the untreated diabetic rats (average: 412.2 mg/dL) and decreased the levels of very low-density lipoproteins (average: 20.4 mg/dL vs. average: 82.44 mg/dL). Regarding oxidative stress markers, the diabetic group treated with diazoxide showed reduced concentrations of thiobarbituric acid reactive substances (TBARS) and total reactive oxygen species. Furthermore, the treatment preserved the concentrations of reduced glutathione, an important antioxidant.

Conclusion: Administration of diazoxide in diabetic rats improved muscle strength development, reduced fatigue, lowered cholesterol and triglyceride levels, and improved oxidative stress parameters such as TBARS, ROS, and glutathione status. These findings suggest that diazoxide may have potential therapeutic benefits in managing the complications associated with diabetes.