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

Eur J Clin Invest 2012; 42 (6): 637–648 Abstract Background  This study was undertaken to evaluate the preventive effect of α‐lipoic acid (LA) on chronic mild portal endotoxaemia‐mediated subacute hepatic inflammation and pancreatic β cell dysfunction in rats. Materials and methods  Male Sprague–Dawley 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 α 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 β cell dysfunction. Conclusions  α‐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.