ObjectiveTo study effect of expression levels of serum inflammatory factors and insulin receptor substrate(IRS)-1/2 in visceral adipose tissue after Roux-en-Y gastric bypass(RYGB) on type 2 diabetes mellitus(T2DM) rats, and explore possible mechanism in treatment of T2DM. MethodsThe T2DM rats models were established, which were divided into 3 groups by intervention: T2MD-RYGB group(n=14), T2MD-sham operation(T2MD-SO) group(n=10), and T2MD group(n=10), and 10 normal rats were selected as control group. The rats of the T2MD-RYGB group were received the RYGB, and of the T2MD-SO group were received transection and reanastomosis of the gastroin-testinal tract. The fasting plasma glucose(FPG), fasting insulin(FINS), C-reaction protein(CRP), tumor necrosis factor-α(TNF-α), free fatty acid(FFA), homestasis model assessment for insulin resistance(HOMA-IR), adipose tissue insulin resistance(Adipo-IR) were tested respectively before operation and on week 1, 4, 8 after operation(synchronous detec-tion of rats with or without surgical intervention). The IRS-1 and IRS-2 protein contents of the rat epididymal adipose tissue were tested on week 8 after operation. ResultsThe FPG, FINS, CRP, TNF-α, FFA levels, and HOMA-IR, Adipo-IR indexes in the T2DM rats were significantly higher than those in the normal rats(P < 0.05) before operation, the above indicators on week 4, 8 after operation were significantly lower than those before operation in the T2MD-RYGB group(P < 0.05). The differences of changes among the other groups were not statistically significant(P > 0.05). The IRS-1 and IRS-2 protein expressions in the adipose tissue of the rats were significantly increased in the T2MD-RYGB group as compared with these indicators in the T2MD group and T2MD-SO group(P < 0.05), but which were significantly lower than those in the control group(P < 0.05). ConclusionsRYGB could increase IRS-1/2 expression levels in adipose tissue, which could enhance insulin sensitivity, decrease serum inflammatory factors levels, and improve insulin resistance ultimately. This might be one of the mechanisms in treatment of T2DM.
ObjectiveTo observe expre with ssions of insulin receptor substrate 1(IRS-1) and ubiquitin-protein in skeletal muscle of non-obese rats with type 2 diabetes mellitus following gastric bypass operation (GBP), and to investigate possible mechanism of GBP in improving insulin resistance. MethodsMale GK rats were randomly divided into diabetic operation group (DO group), diabetic sham operation group (DSO group), and diabetic control group (DC group), 8 rats in each group; besides 8 male Wistar rats were served as normal control group (NC group). Fasting body weight (FBW), fasting plasma glucose (FPG), and fasting insulin (FINS) were measured respectively before operation and on week 1, 2, 4 and 8 after operation. Homeostasis model-insulin resistant (HOMA-IR) index was calculated respectively before operation and on week 8 after operation. The expressions of IRS-1 protein and ubiquitin-protein in skeletal muscle were detected by using Western blot method on week 8 after operation. Results① Compared with the preoperative levels, the FBWs on week 1, 2, and 4 after operation markedly decreased (P < 0.05), but it recovered to the preoperative level on week 8 after operation (P > 0.05) in the DO group; which in the DSO group decreased on week 1 after operation (P < 0.05) and then increased on week 4 after operation (P < 0.05); which in the DC group or the NC group increased continuously and had a significant difference on week 8 after operation (P < 0.05).② The FPGs in the DO, DSO and DC groups were significantly higher than those of the NC group before operation (P < 0.05), which in the DO group decreased from (9.10±0.98) mmoL/L before operation to (5.70±0.91) mmol/L on week 8 after operation (P < 0.05) and were significantly lower than those of the DSO group or the DC group on week 2, 4, and 8 after operation (P < 0.05); which in the DC group, DSO group and NC group had no obviously changes between before and after operations (P > 0.05). ③ The FINS had no significant differences among these four groups before operation (P > 0.05), which in the DO group obviously increased[(9.64±1.59) mU/L] on week 2 after operation (P < 0.05) and then obviously decreased[(6.58±1.05) mU/L] on week 8 after operation (P < 0.05) and significantly lower than those of the DSO group or the DC group on week 8 after operation (P < 0.05), while which had no significant difference between before and after operations in the DSO group, the DC group, or the NC group (P > 0.05). ④ The HOMA-IR index in the DO, DSO or DC group was significantly higher than that of the NC group before operation (P < 0.05), which in the DO group markedly decreased from 3.18±0.50 before operation to 1.96±0.63 on week 8 after operation (P < 0.05) and significantly lower than that of the DSO group or the DC group on week 8 after operation (P < 0.05), while which had no significant difference between before and after operations in the DSO group, the DC group, or the NC group (P > 0.05). ⑤ The expression of IRS-1 protein in the DO group was significantly higher than that in the DSO group (P < 0.05) or the DC group (P < 0.05) on week 8 after operation. While there was no significant difference between the DSO and the DC group after operation (P > 0.05). ⑥ Compared with the NC group, the expression of ubiquitin-protein was significantly increased in the DO group, the DSO group, or the DC group (P < 0.05). Compared with the DSO group or the DC group, the expression of ubiquitin-protein was significantly decreased in the DO group on week 8 after operation (P < 0.05), especially it was most obvious near the molecular weight of 180×103. While there was no significant difference between the DSO group and the DC group after operation (P > 0.05). ConclusionsExpression of IRS-1 protein in skeletal muscle insulin signaling pathway in type 2 diabetes mellitus rats following GBP is increased, it might be associated with decreasing ubiquitin-protein level in skeletal muscle, thus reduces the IRS-1 ubiquitin-degradation, increase insulin sensitivity, and improve insulin resistance of skeletal muscle.