Midaoui Adil El, Talbot Sébastien, Lahjouji Karim, Dias Jenny Pena, Fantus I George, Couture Réjean
Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, PO Box 6128, Station City-Center, Montréal, Qc, H3C 3J7 Canada.
Department of Medicine, Mount Sinai Hospital and University Health Network, Banting and Best Diabetes Center, University of Toronto, Toronto, On, M5G 2C4 Canada.
J Diabetes Metab. 2015 Jun 1;6(6):1-7. doi: 10.4172/2155-6156.1000556.
To investigate the impact of alpha-lipoic acid on superoxide anion production and NADPH oxidase activity as well as on the expression of kinin B1 and B2 receptors in key organs of obese Zucker Diabetic Fatty rats.
Superoxide anion production was measured by lucigenin chemiluminescence. Kinin B1 and B2 receptors expression was measured at protein and mRNA levels by western blot and qRT-PCR in key organs of Zucker Diabetic Fatty and Zucker lean control rats treated for a period of 6 weeks with a standard diet or a diet containing the antioxidant α-lipoic acid (1 g/kg).
Superoxide anion production and NADPH oxidase activity were significantly enhanced in aorta and adipose tissue of Zucker Diabetic Fatty rats. Kinin B1 and B2 receptors expression levels were also significantly increased in the liver and the gastrocnemius muscle of Zucker Diabetic Fatty rats. Expression of both receptors was not altered in the pancreas of Zucker Diabetic Fatty rats and was undetectable in white retroperitoneal adipose tissue. Alpha-lipoic acid prevented the rise in NADPH oxidase activity in aorta and epididymal adipose tissue of Zucker Diabetic Fatty rats and the upregulation of kinin B1 receptor in liver and gastrocnemius muscle and that of kinin B2 receptor in the liver. Alpha-lipoic acid treatment was found to prevent the final body weight increase without affecting significantly hyperglycemia, hyperinsulinemia and insulin resistance index in Zucker Diabetic Fatty rats.
Findings support the hypothesis that oxidative stress is implicated in the induction of kinin B1 receptor in Zucker Diabetic Fatty rats. The ability of α-lipoic acid to blunt the body weight gain appears to be mediated in part by preventing NADPH oxidase activity rise in adipose tissue and reversing the hepatic upregulation of kinin B1 receptor in Zucker Diabetic Fatty rats.
研究α-硫辛酸对肥胖Zucker糖尿病脂肪大鼠关键器官中超氧阴离子生成、NADPH氧化酶活性以及激肽B1和B2受体表达的影响。
采用光泽精化学发光法测定超氧阴离子生成。通过蛋白质印迹法和qRT-PCR在经标准饮食或含抗氧化剂α-硫辛酸（1 g/kg）饮食处理6周的Zucker糖尿病脂肪大鼠和Zucker瘦素对照大鼠的关键器官中，检测激肽B1和B2受体在蛋白质和mRNA水平的表达。
Zucker糖尿病脂肪大鼠的主动脉和脂肪组织中超氧阴离子生成和NADPH氧化酶活性显著增强。Zucker糖尿病脂肪大鼠的肝脏和腓肠肌中激肽B1和B2受体表达水平也显著升高。两种受体在Zucker糖尿病脂肪大鼠的胰腺中表达未改变，在腹膜后白色脂肪组织中未检测到。α-硫辛酸可防止Zucker糖尿病脂肪大鼠主动脉和附睾脂肪组织中NADPH氧化酶活性升高，以及肝脏和腓肠肌中激肽B1受体和肝脏中激肽B2受体的上调。发现α-硫辛酸治疗可防止Zucker糖尿病脂肪大鼠最终体重增加，而不显著影响高血糖、高胰岛素血症和胰岛素抵抗指数。
研究结果支持氧化应激与Zucker糖尿病脂肪大鼠激肽B1受体诱导有关的假说。α-硫辛酸抑制体重增加的能力似乎部分是通过防止脂肪组织中NADPH氧化酶活性升高以及逆转Zucker糖尿病脂肪大鼠肝脏中激肽B1受体的上调来介导的。
