Research On Glucagons-like Peptide-1Regulating Glycolipid Metabolism On Aged Diabetes Mellitus Rat Of Dendrobium Compound

ObjectObserved the influence of dendrobium compound (DC) affected on glucagons-like peptide-1, glycolipid metabolism, reveals the mechanism of DC on natural aging diabetes mellitus rat, it lays the theoretical basis of clinical treatment of diabetes mellitus liver.Methods90Sprague-Dawley female rats of SPF degree, which weigh200±20g,, were randomly divided into2groups:normal control group, molding group. The normal control group was fed with basic diet, and the molding group was fed with high-saturated fat and sugar diet. The normal control group received a celiac injection of physiological saline, the molding group received a celiac injection of streptozotocin (STZ20mg/kg), select the rats whose fasting blood glucose was above16mmol/L to make them control group, then divided the control group into normal control group, model group, compare group(metformin group), low and high dose of DC groups. All of the rats will be killed at the end of24th day, then detection of relevant indexes:(1) The small intestine, pancreas histopathologic sections of HE staining will be observed by the light microscopy;(2) Blood biochemistry was taken to estimate the glucose (GLU), triglyceride (TG),high density lipoprotein (HDL),low density lipoprotein (LDL).cholesterol (CHOL),glycated serum protein (GSP);(3) ELIS A was used to test Glucagon-like protein-1(GLP-1) in0.5and2.5hours;(4) Radioimmunoassay was used to evaluate the expression of fasting insulin, glucagon;(5) Immunohistochemistry was used to evaluate the protein expression of GLP-1,glucorinase, glucose transporter2, insulin;(6) Agilent Whole Rat Genome Oligo Microarray was used to evaluate the expression of the liver. The statistical analysis of the data was done with the statistical package of SPSS16.0.Results1Because of feeding for more than12monthes, the model rats belong to natural aging rats. 2The results of blood biochemistry. analysis showed that:(1) Only by high fat and sugar feed for1year, the expression of GLU and CHOL had no significant difference with the normal control group, p>0.05;(2) The expression of GLU in the DC high and low group were lower markedly than the molding group, p<0.01;(3)The expression of GSP in the DC low group were lower than the molding group,p<0.05; the expression of GSP in the DC high group were lower markedly than the molding group,p<0.01;(4) The expression of CHOL in the DC high and low group were lower markedly than the molding group,p<0.01.3The difference between0.5and2.5hours of GLP-1in the DC low group were lower than the molding group,p<0.05; the difference between0.5and2.5hours of GLP-1in the DC high group were higher markedly than the molding group,p<0.01.4The results of radioimmunoassay showed that:(1) The expression of GLU in the molding group was higher markedly than the normal control group, p<0.01; the expression of GLU in the DC high and low group were lower markedly than the molding group, p<0.01.(2) The expression of INS in the molding group was lower markedly than the normal control group, p <0.01; the expression of INS in the DC high and low group had no significant difference with the molding group, p>0.05.5The results of pathological observation showed that:compared with the normal control group, the number and the areas of islets reduced markedly, atrophy and degeneration morphology appeared in the DC control group rats, the void of the islet tissue in the DC high and low group were significantly less than the model group, and the basophilic material in the cell cytoplasm was increased.6The results of immunohistochemistry showed that:the positive area and IOD of GCK in the DC high and low group were higher markedly than the molding group,p<0.01; the positive area of GLUT-2in the DC high group were higher markedly than the molding group, p<0.01; the positive area of GLUT-2in the DC low group were higher than the molding group, p<0.05;the IOD in the DC high and low group were higher markedly than the molding group, p <0.01.7Agilent Whole Rat Genome Oligo Microarray showed that:there were1678differential gene expressions between the molding group and the normal control group,p<0.05, there were1107differential gene expressions between the DC low group and the molding group, p <0.05, there were665differential gene expressions between the DC low group and the normal control group, p<0.05. Cluster analysis revealed that DC low group was more close to the normal control group.Conclusion1DC can reduce GLU, CHOL, GSP, glucagon levels.2DC can promote the secretion of GLP-1as well as the expression of GCK and GLUT-2, which was one mechanism of the DC regulation of glucose metabolism.3The mechanism of DC treating diabetes mellitus relats to the expression of improving multiple gene pathway.