Inflammatory change of fatty liver induced by intraportal low-dose lipopolysaccharide infusion deteriorates pancreatic insulin secretion in fructose-induced insulin-resistant rats

被引:14
作者
Hsieh, Po-Shiuan [1 ]
机构
[1] Natl Def Med Ctr, Dept Physiol & Biophys, Taipei 114, Taiwan
关键词
chronic steatohepatitis; fatty liver; fructose-fed rats; portal endotoxaemia;
D O I
10.1111/j.1478-3231.2008.01714.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: This study tested whether subacute inflammatory change of fatty liver induced by portal endotoxaemia is detrimental to pancreatic insulin secretion in fructose-fed rats (FFRs) with fatty liver. Methods: Rats were randomly assigned into two groups with a regular or fructose-enriched diet for 8 weeks. Rats, after fructose feeding for 4 weeks, were further divided into three subgroups: on fructose diet alone, on fructose diet combined with intraportal saline or lipopolysaccharide (LPS) infusion (n=8 per group) for the next 4 weeks. In another set of experiments, the liver and pancreatic tissues were obtained for histological examination in these four groups. Pancreatic insulin secretion was evaluated by in vivo hyperglycaemic clamp study. Results: Fasting plasma insulin concentrations and homoeostasis model assessment-insulin resistance, an insulin resistance score, were significantly increased in FFRs but failed to change in rats with LPS treatment. The 4-week intraportal LPS infusion significantly increased circulating aspartate transaminase, alanine transaminase and C-reactive protein levels but did not alter endotoxin levels in FFRs. The increased white blood cell count was also noted in rats after intraportal LPS infusion for 2 and 4 weeks. The attenuated first-phase and second-phase insulin responses in FFRs shown in hyperglycaemic clamp were further deteriorated in those with intraportal LPS infusion. Increased histopathological scores of liver and pancreas shown in FFRs were further increased in those combined with portal endotoxaemia. Conclusion: This study demonstrates that the chronic subacute inflammatory change of fatty liver induced by mild portal endotoxaemia could deteriorate insulin secretion in a rodent model of metabolic syndrome and fatty liver.
引用
收藏
页码:1167 / 1175
页数:9
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