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


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.
Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan. pshsieh@hotmail.com
P-S
PS
Hsieh
J Y-H
JY
Chan
J-F
JF
Shyu
Y-T
YT
Chen
C-H
CH
Loh
D000818:Animals; D019446:Endotoxemia / Q000150:complications*; D006505:Hepatitis / Q000209:etiology* / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D011168:Portal System; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D013481:Superoxides / Q000378:metabolism
D007328:Insulin; D008070:Lipopolysaccharides; D013481:Superoxides