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Research To The Expression Of GLUT4 And PP1 In Liver Cirrhosis

Posted on:2009-08-18Degree:MasterType:Thesis
Country:ChinaCandidate:W F DanFull Text:PDF
GTID:2144360245452969Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Objective:About 60%~80%of patients with liver cirrhosis have glucose intolerance,and 10~20%develop diabetes mellitus(GM)eventually.The concept of hepatic GM had been brought out dating from 1906.Hepatic GM is refered to the diabetes which follows by liver disease or cirrhosis. Its related abnormal glucose metabolism mechanism has not yet been fully clarified.Nowadays,it is widely assumed that insulin resistance may be the main reason.Insulin resistance refers that the reduced response of liver,skeletal muscle and adipose to insulin.The effect to insulin is decreased in the cells with insulin receptors.In other words,it needs extraordinary amount of insulin to maintain normal reaction in cells.Insulin must be bind to the insulin receptor on the membrane which can activate a series of signal transduction system,and ultimately regulating glucose uptake in muscle, fat and liver cells.Then,the blood glucose is reduced by inhibiting gluconeogenesis,increasing glucose utility and glycogen synthesis.In insulin signal transduction systems,glucose transporter-4(GLUT-4)plays a key role.GLUT-4 is the most important glucose transporter,which is responsed to 50-80%of the total amount of the glucose transportation in body.GLUT-4 is only expressed in muscle(mainly skeletal muscle)and adipose cells that are sensitive to insulin.GLUT-4 is mainly in cells in usual.However,with the stimulated by insulin,GLUT-4 quickly is moved to the surface and involved in glucose transportation,then plays a key role in the absorption and utilization of glucose.The obstacle of this process will cause insulin resistance and hyperglycemia.After transported into cells by GLUT4,glucose mainly is transformed to glucogen by glycongen-bound protein phosphatase(PP1). PP1,which is composed of the catalytic subunit(37KDa)and regulating subunit(170KDa),is the main phosphatase in the way of activation of glucose synthesis.The recent study is focus on the regulating subunit, rather than the catalytic subunit.Thus,this research mainly study whether exist insulin resistance in liver cirrhosis and whether occur abnormality of the protein the mRNA contents of GLUT4 and PP1,in order to find out the etiological factors of insulin resistance in liver cirrhosis and provide with theoretical evidence for preferably curing and interventing insulin resistance clinically in liver cirrhosis.Method:We randomly chose 25 healthy persons as normal group and 24 persons who need to cut off spleen because of liver cirrhosis caused by HBV as liver cirrhosis group.①Both groups draw off 6ml blood before anaesthesia.The fasting blood glucose was determined by a fasting blood glucose meter.The samples were standing for 30min and fast centrifuged at the speed of 3000rpm for 10min.The blood serum was removed into an E.P.duct and then was moved into a ultra cold freezer.Biopcies from both groups were analyzed for insulin and C-peptide using chemiluminescent immunoassay.②Small pieces of skeletal muscle were excised from both groups when the operation started.Every specimens were cut into several pieces of 50-100mg,quick-frozen with liquid nitrogen and then removed into a -80℃ultra-low-temperature refrigerator.The protein of GLUT4 and PP1 were determinated by western blot and their gene expression detected by RT-PCR.Results:Fasting blood glucose,insulin,C-peptide values of cirrhosis group are great higher than that of the normal group(P<0.05).The protein contents and gene expressions of PP1g1 change significantly between both groups,while that of GLUT4 don't.Conclusion:1.This study showed that the fasting blood glucose,insulin, C-peptide patients of cirrhosis are great higher than that normal,which confirm that patients with liver cirrhosis are existence insulin resistance.2.The IGT and insulin resistance in cirrhotic patients have no relationship with the contents of protein and mRNA of GLUT4,may be related to the low content of protein and mRNA of PP1g1.
Keywords/Search Tags:liver cirrhosis, insulin resistance, diabetes, PP1, GLUT4
PDF Full Text Request
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