Experimental Research On Effect Of Roux-en-Y Gastric Bypass Surgery On Renal Gluconeogenesis In Obese Rats

Objective:To investigate the effect of Roux-en-Y gastric bypass surgery on renal gluconeogenesis,and to explore the mechanism of improving glucose control and insulin sensitivity in obese rats after surgery.Methods:100 rats were randomly divided into the obese group(n=90)consumed high fat diet(HFD)and left rats consumed low fat diet(LFD)which were induced 16 weeks.Top 30% of animals fed HFD by change in body mass were subdivided into three groups: obese control group(OB group,n=8),obese under RYGB surgery(RYGB group,n=8)or sham operation(Sham group,n=8);Another 8 SD rats fed LFD as normal control(NC group,n=8).Body weight and random blood glucose were regularly measured each week.Body fat percentage was scanned by dual X-ray absorptiometry(DEXA).Intraperitoneal glucose and insulin tolerance test(GTT and ITT)were performed in 15 th and 22 th week.Reagent kits of TC,TG,LDL and HDL were employed for biochemical detection of serum which isolated from blood sample.Fasting blood glucose(FBG),fasting insulin(FINS)and Glucagon Like Peptide 1(GLP1)were respectively measured by oxidized assay and ELASA kit.The area of glucose curve(AUG)and homeostasis model of assessment of insulin resistance index(HOMA-IR)were calculated respectively.The m RNA levels and protein levels of the key enzymes(G6PC and PEPCK)of renal gluconeogenesis were examined with real-time fluorescent quantitative polymerase chain reaction(RT-PCR)and western blot respectively 8th week after surgery.Results:1.Compared with NC group,the level of body mass,fat percentage and random blood glucose were significantly increased in OB group(P<0.05);The blood glucose of FBG and 2h in GTT or ITT in OB group were significantly increased than those in NC group before surgery(P<0.05).Compared with OB group and Sham group,the level of body mass,fat percentage and random blood glucose were significantly decreased in RYGB group(P<0.05);The blood glucose of FBG and 2h in GTT or ITT in OB and Sham group were significantly increased than those in RYGB group after surgery(P<0.05).2.Compared with OB group and Sham group,the level of TC,TG and LDL were significantly decreased in RYGB group(P<0.05).HE-stained organizations were observed that the OB and Sham group organizational structure of the kidney were abnormal.Those pathologic changes in RYGB groups were significantly improved.Compared with OB group and Sham group,the level of FBG,FINS and HOMA-IR were significantly decreased(P<0.05)and GLP-1 was increased in RYGB group(P<0.05).3.Compared with OB group and Sham group,the expression of G6 PC and PEPCK m RNA and protein were significantly reduced(P<0.05)and the expression of p-IRS1 and p-Akt were increased in RYGB group(P<0.05).Conclusions:Roux-en-Y gastric bypass surgery can improve glucose control and insulin resistance,which may be related to decrease levels of m RNA and protein of G6 P and PEPCK,weaken gluconeogenesis and glucose output in renal cortex.