Mechanisms Of DJB Treat Non Obese T2DM Rats And Prevent Its Complication Of Aortic

BACKGROUND AND OBJECTIVES Type2diabetes mellitus(T2DM)is a rife endocrine metabolism disease. In the conventional treatment,including diet control, exercise, oral hypoglycemic drugs, injection ofinsulin, glucose homeostasis rarely keep in a long time, various compli-cations tend to appear. At the end of the last century，GBP can remit T2DMwas found out in the treatment of obesity, and further study found that GBPcan not only treat T2DM patients with obese, but also prevent theoccurrence of complications. However, for a large number of non-obesepatients with T2DM, whether GBP has the same effect is not clear.As a modified procedure of GBP, DJB, does not restrict food intake,which can achieve the effect of food bypass, avoid any significant weightloss in non obese patients with T2DM. To confirm whether DJB can remitthe T2DM in non obese patients, more animal, multicenter clinicalexperiments need to be carry out.In this study, firstly, we investigate the therapeutic effect of DJB innon obese T2DM rats through the observation of blood glucose, blood lipidchanges before and after DJB. Secondly, we explore the possible therapeutic mechanism by detecting the expression of GLP-1in ileal L cells,the change of endoplasmic reticulum stress and inflammatory signalingpathway in liver and pancreatic. At last, we investigate the prevention andtreatment of DJB on diabetic complications of aortic and its possiblemechanism by observing rat aortic morphology changes and inflammatorysignaling pathway changes.METHODS (1) A T2DM model was established using high fat and highsugar diet and intraperitoneal injection of low dose of streptozotocin in SDrats. Diabetic rats were divided into the DJB group, sham operation group,T2DM control group, and normal SD rats in control group, first two groupswere implemented in DJB operation and false operation. Postoperative12weeks, the changes of blood glucose, lipid, FINS and TNF-α were collectedto observe the effect of DJB on remitting T2DM and the morphologicalchanges of pancreatic islets in rats. Immunohistochemistry was used todetect the expression GLP-1protein in ileal L cells in rats of each group.(2)12weeks after operation, liver and pancreatic tissues in each groupwere collected. Then, qPCR was performed to examine the changes ofPERK, eIF2α, IRE1, IKKβ, JNK1mRNA in each group, and western-blotwas performed to examine the changes of PERK, eIF2α/p-eIF2α, IRE1,IKKβ/p-IKKβ, JNK1/p-JNK1protein in each group.(3) Aortic morphology changes in each group rats were observed12weeks after operation. QPCR was performed to examine the changes of IKKβ, JNK1mRNA in aortic, and western-blot was performed to detect theexpression of IKKβ/p-IKKβ, JNK1/p-JNK1protein in aortic in each group.RESULTS (1) Non obese T2DM rat model was successfully established in66.7%SD rats. In T2DM rats, DJB and sham operation model weresuccessfully established too.12weeks after operation, blood glucose, lipid,INS and TNF-α in DJB group significantly decreased, the insulin resistanceameliorated, body weight increased and returned to normal. The pancreaticislet morphology became irregular in T2DM control group, sham operationgroup rats. The expression of GLP-1protein in ileal L cells in DJB groupwas the strongest among the four groups, the secondly was the normal SDrats control group, there had no distinction between T2DM group and shamoperation group.(2) In the liver and pancreatic tissues, the expression of PERK, eIF2α,IRE1, IKKβ, JNK1mRNA and PERK, eIF2α/p-eIF2α, IRE1, IKKβ/p-IKKβ, JNK1/p-JNK1protein in the DJB group were lower than theT2DM group or sham operation group. While there had no obviousdifference between the T2DM group and sham operation group.(3) Aortics showed just minor damage in DJB group, while shamoperation group and T2DM group appeared in foam cells or atheroscleroticplaque. The expression of IKKβ, JNK1mRNA and IKKβ/p-IKKβ, JNK1/p-JNK1protein of aortic in DJB group were significantly lower than thesham operation control group or T2DM group. CONCLUSIONS The non obese rats T2DM model induced by high fatand high sugar diet combined with low dose streptozotocin is a good modelfor research the effect of DJB treating T2DM. DJB has a definitetherapeutic effect on non obese T2DM rats of artificial induction. DJB mayplay its role by stimulating ileal L cells secrete more GLP-1to regulate theendoplasmic reticulum stress in diabetic rats’ liver and pancreas, inhibitingNF-κB and JNK signal pathway. DJB has a protective effect againstatherosclerosis in non obese T2DM rats’ aortic, through inhibiting NF-κB,JNK signal pathway.