| Background and purposeGlucose intolerance is frequently observed in patients with advanced liver cirrhosis and the patients suffer complications of cirrhosis more frequently as well as increased mortality. It is suggested that insulin resistance predominantly occurs in peripheral tissue and especially glucose uptake diminished in muscular tissue. However, to date, the underlying molecular mechanisms remain elusive. It is proved that PI3K/Akt cascade is the main insulin signalling pathway. The aim of this study was to investigate the effects of liver cirrhosis in glucose metabolism and PI3K/Akt pathway in skeletal muscle of cirrhotic rat model.MethodsSpecific pathogen-free male Sprague-Dawley rats were randomized to two groups, bile duct ligation group and sham laparotomy group. OGTT were performed on thirtieth two day after surgery. Three days after the OGTT, the rats were sacrificed and extensor digitorum longus muscles were carefully isolated and divided into four muscle fiber bundles immediately. And then they were incubated in essential buffer without (basal) or with increasing concentrations of insulin for60min. Basal and insulin-stimulated extensor digitorum longus muscles were collected by removing the medium and quickly freezing in liquid N2. We evaluate the effect of liver cirrhosis on PI3K/Akt pathway by detecting pAkt/Akt and pAS160/AS160. ResultsIn cirrhotic rat models, glucose intolerance is existing (P<0.5). The expression of Akt and AS160proteins contents appeared to be normal and Akt phosphorylation was unchanged (P>0.5). Moreover, AS160phosphorylation at Thr642residue was impaired after insulin stimulated (P<0.05).ConclusionDisturbed phosphorylation at Thr642on AS160may in part explain insulin resistance at molecular level in skeletal muscle in the rat model of liver cirrhosis. |
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