Effects Of Exendin-4 On Hepatic Glycogen In The Rats With Impaired Glucose Tolerance

Objective:To compare the changes of glucose transporter(GLUT2) and glycogen in impired glucosetolerance(IGT) rats after intervention with exendin-4,and to analyze the correlation between GLUT2 and glycogen,to investigate the mechanisms of exendin-4 improvement glycogen synthesis.Methods:54 Wistar rats were used as test object, the subjects were feerly separate in 2 groups,one group(normal) have 18, another group(model) has 36, Normal group were fed with food which of the fats provide 10.3% of calories, protein was 23.7% of calories, and sugar provide 66.0% of calories. Model group were fed with foods with high amounts of sugars,fats according to the same method to mix, fats provide 56% of calories, protein provide7.0% of calories, and sugar provide 37% of calories[1].All rats do not restrict water and activity, to hurl food 2 times a day. Feed until 184 days, the day before stopping feeding,and the next day after eight hours on an empty stomach, vein blood of rats were selected to detect fasting blood glucose(FBG) and postprandial blood glucose(PBG), tendency at 7.8mmol/l and 11.1mmol/ l were considerd as successful model group[1]. The first group rats of blood glucose was normal,and being set to normal glucose tolerance groups(NGT group,n=18) and continue to feed regular food. Twenty eight rats of the second group were set into models, model success rats is 78%. The subjects were feerly separate in 2 groups,exendin-4 intervention group(IGT+Na Cl group,n=14) and the impaired tolerancegroup(IGT+Na Cl group,n=14) and were given high sugar-high fat diet. The IGT+Ex group of rats received exendin-4 5ug/kg subcutaneously, twice daily, and the NGT groups and IGT+Na Cl group were given equal volume of saline injection. After four weeks,all rats do OGTT test, measure FBG and PBG,also measure TG and TC. Next day the animals were slaughtered,Then quickly remove liver to measure the expression of GLUT2 using immunohistochemical staining methods; observe the change of glycogen in liver using PAS staining methods. GLUT2 color using the IPP6.0 system, according to the glucose transporter 2 markers of liver cells positive area percentage of quantitative analysis, the 5view of each specimen were randomly selected, taking the average value of statistical analysis;after liver glycogen PAS staining with pathologic microscopic analysis system for quantitative analysis(each group of randomly selected 3×3 vision, determination of ×200in each view glycogen particles area percentage).All results were measured by( x ±s), using SPSS 17.0, multiple group means were used LSD-t test.P<0.05 was considered statistically significant.Results:The change of glucose levels and blood lipid levels in each group:After interve ntion, compared with IGT+Na Cl groups, the PBG, the TG and TC of rats in IGT+Ex group were decreased(10.38±0.38 vs.7.17±0.36)(2.24±0.16 vs.1.06±0.13)(2.11±0.19 vs.1.02±0.09),differences were significant(both P<0.05);FBG(5.08±0.46 vs.5.04±0.47) of differences were not significant(P>0.05).Compared with NGT groups,the FBG,PBG,TG and TC of rats(4.86±0.52 vs.5.04±0.47)(5.76±0.54 vs.7.17±0.36)(0.88±0.22 vs.1.06±0.13)(0.84±0.19 vs.1.02±0.09) the differences were not significant(P>0.05).The express ion of GLUT2 in each group:After intervention,compared with IGT+Na Cl groups,the GLUT2 expression of rats in IGT+Ex groups was increased(30.93±2.57 vs.17.70±2.26)(30.93±2.57 vs.17.71±3.51),difference were significant(both P<0.05).Compared with NGT groups,GLUT2 expression of rats had no differences(32.64±4.28 vs.30.93±2.57)P>0.05).Comparison of the glycogen in each groups: after intervention compared with IGT+Na Cl groups,the hepatic glycogen in IGT+Ex groups of rats were increa sed(37.62±5.36 vs.17.95±3.05)(37.62±5.36 vs.18.2±5.63),the differences were significant(both P<0.05).Compared with NGT groups, hepatic glycogen content of Ex group had no differences(44.28±5.85 vs.37.62±5.36,P>0.05).Conclusions:Glucose transportor 2 expression of the rats with impaired glucose tolerance was down regulated, the content of glycogen in liver was also reduced;Exendin-4 can increase the IGT rat liver glycogen reserves, improve glucose metabolism, its mechanism may be related to increase hepatic cell surface expression of GLUT2.