| Background and purposeGlucagon-Like Peptide 1(GLP-1)is a gastrointestinal hormone secreted and released by intestinal L cells,and its physiological effects including promoting the synthesis and release of insulin,stimulating the regeneration and proliferation of pancreatic beta islet cell,inhibiting the secretion of glucagon by islet a cells,delaying gastric emptying,decreasing appetite,increasing satiety,protecting endothelial cells and preventing atherosclerosis and so on.GLP-1 also can lower the level of glucose and blood pressure,protect the kidney,weight loss and protects the cardiovascular system.GLP-1 exerts its physiological function through GLP-1 receptor(GLP-1R).GLP-1R is widely distributed in multiple organs and systems of body,such as gastrointestinal tract,pancreas,heart,smooth muscle,proximal tubule,glomerulus,nervous system and so on,therefore,GLP-1 has a regulatory effect on multiple organs and systems of the body.However,GLP-1 is rapidly degraded by Dipeptidyl Peptidase-Ⅳ(DPP-Ⅳ),so its half-life is only 1～2 minutes.And GLP-1 secreted by L cells decreases in diabetic patients.GLP-1 Receptor Agonist(GLP-1RA)is a homologous analogue of GLP-1,and is the product through modifying the molecular structure of GLP-1,so it has the same physiological effect as GLP-1.With a long half-life,GLP-1RA has pharmacologic therapeutic effect on the body.The patients complicated with type 2 diabetes mellitus(T2DM)and non-alcoholic fatty liver disease(NAFLD)are gradually increasing in clinic,but the drugs aimed at such diseases are limited.Previous studies had shown that GLP-1RA could recovered the non-alcoholic fatty liver disease.This study discusses the effect of GLP-1RA on rats complicated with T2DM and NAFLD through inducing the model of rats complicated with T2DM and NAFLD and using the Liraglutide to intervene the model,and it can provide more experimental basis for the clinical application of such drugs.We hope that we could find the drugs to treat T2DM complicated with NAFLD through constantly experimental exploration.MethodsThe rats were divided into normal feeding group,model group,GLP-1RA group randomly.The rats from model group and GLP-1RA group were used to build the model of rats complicated with T2DM and NAFLD by the way of combining high-fat diet with Streptozotocin(STZ).The Rats in GLP-1RA group were given Liraglutide intraperitoneally after building the model successfully.After 4 weeks,Alanine aminotransferase(ALT)、Total cholesterol(TC)、Triglyceride(TG)、Glucose(GLU)、Glycated serum protein(GSP)were detected after drawing blood from the abdominal aorta of all rats.The whole liver tissues of all rats were taken out,and the weight of every liver was measured,so that the liver index could be calculated.A part of the liver tissue was taken for pathological examination,Superoxide dismutase(SOD)and Malondialdehyde(MDA)were detected by the homogenate of another part of liver tissue.The remaining liver tissue was stored at low temperature after quick freezing in liquid nitrogen.Results1.GLP-1RA can improve the general condition of rats complicated with T2DM and NAFLD,including body weight,hair,mental status,diet,water intake and defecation status.2.The weight of rats in the model group and GLP-1RA group increased significantly compared with that in the normal feeding group(P<0.01),and the weight of rats in the GLP-1RA group decreased compared with that in the model group(P<0.05).Compared with the normal feeding group,the liver index of rats in the model group was significantly increased(P<0.01),while that in the GLP-1RA group was increased(P<0.05).3.ALT,TC,TG,GLU,MDA and GSP of rats in the model group were significantly higher than those in the normal feeding group(P<0.01),while ALT,TC,TG,GLU,MDA and GSP of rats in the GLP-1RA group were significantly lower than those in the model group(P<0.01).SOD of rats in the model group decreased compared with that in the normal feeding group(P<0.05),and SOD of rats in the GLP-1RA group increased compared with that in the model group(P<0.05).4.The hepatocyte of rats in three groups after HE staining and oil red O staining showed that,compared with the model group,the structure of hepatic lobule of rats in GLP-1RA group was more intact and clear,the degree of hepatic steatosis was relieved,and the lipid droplets in the cells seen by the naked eye were obviously decreased.ConclusionGLP-1RA has beneficial effects on rats complicated with T2DM and NAFLD,which not only has positive effects on the general situation of rats,but also regulates the metabolism of glucose and lipid,resists oxidative stress,protects the function of liver,reduces deposit lipid in hepatocyte,and delays the progress of non-alcoholic fatty liver.The NAFLD activity score of rats in GLP-1RA group was significantly lower than that in the model group. |
PDF Full Text Request