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Mild portal endotoxaemia induces subacute hepatic inflammation and pancreatic beta-cell dysfunction in rats.

Abstract：

BACKGROUND:Portal endotoxaemia has been speculated to be crucially involved in the pathogenesis of chronic hepatic inflammation, which is highly associated with the development of type 2 diabetes mellitus. This study tests whether portal endotoxaemia is a pathogenic link between chronic subacute hepatic inflammation and pancreatic beta-cell dysfunction. MATERIALS AND METHODS:Rats were randomly assigned into two groups: rats with intraportal saline or low-dose lipopolysaccharide (LPS) infusion for 4 weeks. Pathological changes in the liver were evaluated via histological and biochemical examination. Pancreatic insulin secretion was evaluated by in vivo hyperglycaemic clamp study. RESULTS:White blood cell count was significantly increased after intraportal LPS infusion for 4 weeks. Plasma amylase and chemoluminescence counts indicating superoxide levels were significantly increased after LPS treatments for 2 and 4 weeks. Intraportal low-dose LPS infusion significantly increased tumour necrosis factor-alpha and interleukin-6 contents in liver and pancreas. Circulating C-reactive protein, thiobarbituric acid reactive substances (TBARS) and endotoxin levels were not different among groups. The first- and second-phase insulin secretions in hyperglycaemic clamp were significantly decreased in LPS-treated rats. The histopathological scores, de novo production of reactive oxygen substrate and TBARS contents in the liver and pancreas were significantly increased in LPS-infused rats. Leucocyte infiltration was clearly visible in pancreatic islets of LPS-treated rats. CONCLUSIONS:The present study demonstrated that mild portal endotoxaemia caused subacute hepatic inflammation and impaired pancreatic insulin secretion, implicating that portal endotoxaemia is a potential risk factor to link chronic subacute hepatic inflammation and pancreatic beta-cell dysfunction.

journal_name

Eur J Clin Invest

journal_title

European journal of clinical investigation

authors

Hsieh PS,Chan JY,Shyu JF,Chen YT,Loh CH

doi

10.1111/j.1365-2362.2008.01991.x

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

640-8

issue

eissn

0014-2972

issn

1365-2362

pii

ECI1991

journal_volume

pub_type

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Mild portal endotoxaemia induces subacute hepatic inflammation and pancreatic beta-cell dysfunction in rats.