α-Lipoic acid prevents mild portal endotoxaemia-induced hepatic inflammation and β cell dysfunction

Eur J Clin Invest 2012; 42 (6): 637648 Abstract Background This study was undertaken to evaluate the preventive effect of a-lipoic acid (LA) on chronic mild portal endotoxaemia-mediated subacute hepatic inflammation and pancreatic beta cell dysfunction in rats. Materials and methods Male SpragueDawley rats were randomly assigned into four groups: those with intraportal vehicle (saline) or low-dose lipopolysaccharide (LPS) (0.42 ng/kg/min) infusion, combined with oral administration of vehicle or LA, a potent antioxidant (60 mg/kg/day) for 4 weeks. The hyperglycaemic clamp and euglycaemic clamp techniques were used to access the glucose-stimulated insulin secretion and systemic insulin sensitivity in vivo. Results Body weight, fasting plasma glucose and insulin were not different among groups. In rats with chronic intraportal LPS infusion, plasma C-reactive protein, amylase, superoxide levels, the contents of thiobarbituric acid-reactive substance, tumour necrosis factor a and interleukin 6 in liver and pancreas and also the gene expression of Toll-like receptor 4 in liver were significantly increased as compared with those with LA cotreatment. The histopathological examination showed that inflammatory changes were clearly visible in liver and pancreatic islets of LPS-infused rats and rarely observed in those cotreated with LA. In addition, low-dose intraportal LPS infusion also significantly impaired glucose-stimulated insulin secretion but not affect the systemic insulin sensitivity and metabolic clearance rate of insulin. LA administration markedly reversed LPS-induced beta cell dysfunction. Conclusions a-Lipoic acid cotreatment could significantly prevent mild portal endotoxaemia-induced chronic hepatic inflammation and impaired pancreatic insulin secretion in absence of changing systemic insulin resistance.