The Mechanisms Of Roux-en-Y Gastric Bypass For Improved Insulin Resistance In Type 2 Diabetic Rats

Objective: To investigate the effect of Roux-en-Y gastric bypass(RYGB) surgery on high-fat diet and strepozotocin(STZ) induced type 2 diabetic SD rats and normal mice. Through dynamic observation of fasting blood glucose,serum lipid,fasting plasma insulin,and inflammatory cytokines pre- and post-operative respectively to evaluate the improvement of insulin resistance.Meanwhile,the expression of GLUT-4 in the peripheral tissue was measured.To explore preliminaryly the possible mechanism of the improvement of insulin resistance after surgical treatment.Methods: 20 type 2 diabetes mellitus animal model in rats were induced by diets and strepozotocin.Twenty type 2 diabetic rats and twenty SD rats were randomized into four groups : RYGB type 2 diabetes-operation group(DRO group), type 2 diabetes-sham operation group(DSO group), RYGB normal-operation group(NRO group),normal-sham operation group(NSO group),each group had 10 rats.Body weight,serum lipid,fasting plasma glucose,plasma insulin and plasma a-TNF were detected before and after surgery.The protein level of GLUT-4 in the adipose tissue was determined via western blotting method.Results: (1)The Survival condition of rats post-operative:Ten in each group preoperative, eight rats in the DRO group remained after eight weeks of operation; eight rats in the DSO group remained; seven rats in the NRO group remained; eight rats in the NSO group remained. (2)The change of body weight pre- and post-operative:The post-operative body weight in DRO group decreased gradually,but showed no differences significantly(P>0.05).The post-operative body weight of DSO group, NRO group and NSO group increased continuously, and the body weights after surgery were significantly higher than that before surgery, which showed statistically significant differences(P<0.05).(3)The change of FBG pre- and post-operative FBG:Compared with the status of preoperative, FBG in DRO group decreased from 22.238±4.130 mmol/l to 18.925±3.759 mmol/l four weeks later(P<0.05), and further reduced to 9.400±2.489 mmol/l after eight weeks postoperative(P<0.05);the FBG in DSO group was markedly higher than the one of DRO group eight weeks later(P<0.05); the FBG in DSO group, NRO group and NSO group had no obviously changes postoperatively(P>0.05).(4) The level of Triglyceride,Total cholesterol pre- and post-operative:Compared with the status of pre-operative, the level of triglyceride,total cholesterol in DRO group decreased from 2.29±0.19mmol/l,1.80±0.29 mmol/l decreases to 1.61±0.44 mmol/l(P<0.05),1.56±0.23mmol/l(P<0.05)four weeks later respectively, and further decreased to 1.02±0.32 mmol/(lP<0.05),1.12±0.19 mmol/(lP<0.05) respectively eight weeks later;the level of triglyceride,total cholesterol in DSO group were higher than the one of DRO group eight weeks postoperative(P<0.05); the level of triglyceride,total cholesterol in DSO group postoperative eight weeks later were higher than that of preoperative(P<0.05); the level of triglyceride,total cholesterol in NRO group and NSO group had no significant changes pre- and postoperatively(.5)The INS level of pre- and post-operative: Compared with the condition of preoperative,the fasting plasma INS in DRO group decreased from 2.559±3.684mIU/L to 9.828±3.942mIU/ four weeks postoperative(P>0.05), and further decreased to 16.785±2.517 mIU/L eight weeks later(P<0.05);the fasting plasma INS in DSO group was markedly higher than the one of DRO group eight weeks postoperative(P<0.05),the fasting plasma INS in DSO group, NRO group and NSO group showed no significant changes postoperatively.(6) The HOMA-IR pre- and post-operative: Before surgery the HOMA-IR in DRO group and DSO group were markedly higher than the one of NRO group and NSO group(P<0.05). The HOMA-IR in DRO group reduced obviously eight weeks postoperativ(eP<0.05),the HOMA-IR in DSO group was higher than the one of DRO group eight weeks postoperative(P<0.05).DSO group,NRO group and NSO group had no significant changes postoperatively regarding the HOMA-IR..(7) The change of TNF-αpre- and postoperative: Compared with the preoperative,TNF-αin DRO group decreased from 138.42±22.42pg/ml to 115.866±13.60pg/ml four weeks postoperative(P>0.05),and further decreased to 91.27±3.44 pg/ml eight weeks postoperative(P<0.05); TNF-αin DSO group was markedly higher than the one of DRO group eight weeks postoperative(P<0.05); The TNF-αin DSO group was apparently higher eight weeks postoperative(P<0.05),NRO group and NSO group had no significant difference between pre- and postoperatively. (8) The comparison of GLUT-4 expression in rats adipose tissue after surgery: GLUT-4 expression in rats adipose tissue in DRO group was obviously higher than that of DSO group eight weeks postoperative(P<0.05),there was no significant difference between DRO and NRO group and NSO group after surgery.(P>0.05).Conclusion:1. The study found that the rat model of type 2 diabetes established with conjunctive treatment of low-dose SZT after high fat diet easily attainable and inexpensive ,would help further elucidation of the underlying mechanisms of diabetes and its complications.2. After RYGB surgery,the value of fasting blood glucose, serum lipids, serum insulin levels , serum TNF-αlevels in rats with type 2 diabetes were significantly lower than preoperative ones; insulin resistance index(HOMA-IR) ameliorated.The RYGB surgery have an evident effects on type 2 diabetic rats.3. The elevated GLUT-4 expression in adipose tissue and the reduces serum TNF-αpostoperative may be the one of the possible mechanisms for the improvement of insulin resistance after RYGB surgery on type diabetic rats.