Influence and mechanism of the change of IRS-1 and IRS-2 expressions on fasting blood glucose and insulin resistance in diabetic rats after gastric bypass surgery

doi:10.3877/cma.j.issn.2095-9605.2016.04.008

Abstract

Abstract:

Objective

To investigate the influence and mechanism of the change of insulin receptor substrate (IRS)-1 and IRS-2 expressions on fasting plasma glucose and insulin resistance in diabetic rats after Roux-en-Y gastric bypass (RYGB).

Methods

Thirty diabetic Wistar rats were randomized into the RYGB group, sham operation group and diet control group by random number table method with 10 rats in each group, and 10 normal Wistar rats in the same weeks old were picked up as the blank control group. The rats in the RYGB group underwent RYGB, the rats in the sham operation group underwent the operation in which gastric wall and jejunum were cut and then sutured in the original locations, the food intake of the diet control group rats was as much as those of the RYGB group rats 1 day before, and the rats in the blank control group ate as much normal feedstuff as they liked. Fasting plasma glucose (FPG), fasting insulin (FIns), homeostatic model assessment of insulin resistance (HOMA-IR) were tested before and 1, 2, 3, 4 weeks after operation. Then all the rates were killed, their skeletal muscle, liver and pancreas were taken out. The expressions of IRS-1 and IRS-2 in the skeletal muscle and liver were detected by Western blot, and the expression of IRS-2 in the pancreas was detected by immunohistochemistry. The comparisons among the 4 groups were conducted using one-way ANOVA analysis, with LSD-t test for pairwise comparison; and the data between two sets in the same group were compared using t test; and the positive expression rates of IRS-2 in pancreas among 4 groups were compared using χ² test.

Results

In the fourth week after operation, the FPG level of the RYGB group was significantly lower than that before operation (t=30.617, P<0.05), and also lower than that of the sham operation and diet control groups in the same period (LSD-t=12.112, 10.095, P<0.05); but had no statistical difference with that of the blank control group (LSD-t=0.347, P>0.05). In addition, the HOMA-IR level of the RYGB group was significantly lower than that before operation (t=8.631, P<0.05), and also lower than that of the sham operation and diet control groups (LSD-t=7.713, 7.931, P<0.05); but had no statistical difference with that of the blank control group (LSD-t=0.822, P>0.05). Four weeks after operation, the expressions of IRS-1 and p-IRS-1 in skeletal muscle of the RYGB group rats were significantly higher than that of the sham operation and diet control groups (P<0.05); the expression of IRS-2 in liver of the RYGB group rats was lower than that of the sham operation and diet control groups (P<0.05), but slightly higher than that of the blank control group; and the positive expression rate of IRS-2 in pancreas of the RYGB group rats was 76%, which was significantly higher than 2% of the diet control group, 3% of the sham operation group and 44% of the blank control group (χ²=230.181, 222.994, 42.667, P<0.05).

Conclusion

RYGB can cause the change of IRS-1 and IRS-2 expressions in related target organs, which may be one of the mechanisms to improve insulin resistance and decrease fasting plasma glucose in type 2 diabetes mellitus.

Key words: Diabetes mellitus, type 2, Roux-en-Y gastric bypass, Insulin receptor substrate, Insulin resistance, Fasting plasma glucose

Long Li, Yu Li, Yanbing Zhou, Cunlong Lu. Influence and mechanism of the change of IRS-1 and IRS-2 expressions on fasting blood glucose and insulin resistance in diabetic rats after gastric bypass surgery[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2016, 02(04): 219-224.

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References 18

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组别	例数	术前	术后第1周	术后第2周	术后第3周	术后第4周
RYGB组	10	9.3±0.7	5.6±0.9	4.3±0.6	5.1±0.6	4.3±0.6
假手术组	10	9.0±0.4	8.2±0.8^a	9.1±0.6^a	9.8±0.8^a	10.1±0.9^a
饮食对照组	10	9.2±0.6	8.1±0.6^b	8.2±0.8^b	8.4±0.6^b	8.3±0.7^b
空白对照组	10	4.7±0.7	4.3±0.5	4.9±0.6^c	4.8±0.5^c	4.4±0.4^c
F值	?	78.413	256.583	378.132	468.504	533.474
P值	?	<0.05	<0.05	<0.05	<0.05	<0.05

组别	例数	术前	术后第1周	术后第2周	术后第3周	术后第4周
RYGB组	10	9.3±0.7	5.6±0.9	4.3±0.6	5.1±0.6	4.3±0.6
假手术组	10	9.0±0.4	8.2±0.8^a	9.1±0.6^a	9.8±0.8^a	10.1±0.9^a
饮食对照组	10	9.2±0.6	8.1±0.6^b	8.2±0.8^b	8.4±0.6^b	8.3±0.7^b
空白对照组	10	4.7±0.7	4.3±0.5	4.9±0.6^c	4.8±0.5^c	4.4±0.4^c
F值	?	78.413	256.583	378.132	468.504	533.474
P值	?	<0.05	<0.05	<0.05	<0.05	<0.05

组别	例数	术前	术后4周
RYGB组	10	5.64±0.75	1.44±0.31
假手术组	10	4.92±0.67	5.47±0.83^a
饮食对照组	10	5.28±0.53	5.00±0.64^b
空白对照组	10	1.31±0.36	1.25±0.25^c
F值	?	353.416	261.631
P值	?	<0.05	<0.05

组别	例数	术前	术后4周
RYGB组	10	5.64±0.75	1.44±0.31
假手术组	10	4.92±0.67	5.47±0.83^a
饮食对照组	10	5.28±0.53	5.00±0.64^b
空白对照组	10	1.31±0.36	1.25±0.25^c
F值	?	353.416	261.631
P值	?	<0.05	<0.05

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