Abstract
ObjectiveTo 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.MethodsSuperoxide 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).ResultsSuperoxide 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.ConclusionFindings 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.
Highlights
Diabetes mellitus (DM) is defined by the World Health Organisation (WHO) as a metabolic disorder of multiple etiology
The present study demonstrated that the treatment with lipoic acid (LA) prevented the increased expression of B1 receptor (B1R) along with the enhanced basal production of superoxide anion and NADPH oxidase activity in Zucker Diabetic Fatty (ZDF), supporting that the oxidative stress is implicated in the induction and up-regulation of B1R in ZDF rats
The present study demonstrated that supplementation diet with LA prevented the upregulation of B1R in the liver and the gastrocnemius muscle indicating that oxidative stress is implicated in the induction of B1R in ZDF rats
Summary
Diabetes mellitus (DM) is defined by the World Health Organisation (WHO) as a metabolic disorder of multiple etiology. The global figure of people with diabetes is projected to increase to 333 million in 2025, and 430 million in 2030 [1]. Previous studies have suggested that increased superoxide anion production may be involved in the pathogenesis and complications of diabetes and hypertension [3,4]. Studies have shown that α-lipoic acid (LA), which is a powerful antioxidant, improved the insulin sensitivity in patients with type 2 diabetes [5]. The treatment of insulin-resistant Zucker rats with α-lipoic acid was found to increase both oxidative and non-oxidative glucose metabolism and to reduce insulin resistance [6]. In obese patients with impaired glucose tolerance and dyslipidaemia, short-term treatment with LA (600 mg intravenously once daily over a period of 2 weeks) improved the insulin sensitivity and the plasma lipid profile [11]. The same treatment was found to decrease the levels of MDA, 8-isoprostaglandin, TNF-α and IL-6 [11]
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