α-Lipoic acid prevents mild portal endotoxaemia-induced hepatic inflammation and β cell dysfunction
Version of Record online: 29 NOV 2011
© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 42, Issue 6, pages 637–648, June 2012
How to Cite
Tian, Y.-F., Hsieh, C.-H., Hsieh, Y.-J., Chen, Y.-T., Peng, Y.-J. and Hsieh, P.-S. (2012), α-Lipoic acid prevents mild portal endotoxaemia-induced hepatic inflammation and β cell dysfunction. European Journal of Clinical Investigation, 42: 637–648. doi: 10.1111/j.1365-2362.2011.02630.x
- Issue online: 12 MAY 2012
- Version of Record online: 29 NOV 2011
- Accepted manuscript online: 16 NOV 2011 10:19AM EST
- Received 5 September 2011; accepted 3 November 2011
- α-Lipoic acid;
- beta cell dysfunction;
- chronic hepatic inflammation;
- oxidative stress;
- portal endotoxaemia
Eur J Clin Invest 2012; 42 (6): 637–648
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.