Effect of Roux-en-Y Gastric Bypass on Expression of Inflammatory Factors and Insulin Receptor Substrate-1/2 in Adipose Tissue of Type 2 Diabetes Mellitus Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHANGLi-hai , XIABin , WANGJiao , HUANGWen-li ,  WANGYue-sheng , LIUChun-yu , TANBai-hong , YINYan-bin , ZHAOBing-bing

Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi 154003, Heilongjiang Province, China;

Corresponding author：

WANGYue-sheng, Email: wys9906@163.com

Keywords：

Roux-en-Y gastric bypass surgery; Type 2 diabetes mellitus; Adipose tissue; Insulin resistance; Insulin receptor substrate

DOI：

10.7507/1007-9424.20150382

Video：

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Objective To 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. Methods The 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. Results The 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). Conclusions RYGB 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.

Citation： ZHANGLi-hai, XIABin, WANGJiao, HUANGWen-li, WANGYue-sheng, LIUChun-yu, TANBai-hong, YINYan-bin, ZHAOBing-bing. Effect of Roux-en-Y Gastric Bypass on Expression of Inflammatory Factors and Insulin Receptor Substrate-1/2 in Adipose Tissue of Type 2 Diabetes Mellitus Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(12): 1460-1465. doi: 10.7507/1007-9424.20150382 Copy

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2.	Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a syste-matic review and meta-analysis. JAMA, 2004, 292(14): 1724-1737.
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7.	陈若平.减肥手术治疗2型糖尿病的研究进展.中国临床医生, 2014, 42(8): 21-23.
8.	Peterli R, Wölnerhanssen B, Peters T, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg, 2009, 250(2): 234-241.
9.	Bikman BT, Zheng D, Pories WJ, et al. Mechanism for improved insulin sensitivity after gastric bypass surgery. J Clin Endocrinol Metab, 2008, 93(12): 4656-4663.
10.	王勇, 白洁, 匡立润, 等. Roux-en-Y胃旁路术对GK大鼠骨骼肌组织胰岛素抵抗影响的机制研究.中国普外基础与临床杂志, 2014, 21(2): 162-167.
11.	文艺, 祁巧, 汤礼军, 等. Roux-en-Y胃旁路术对2型糖尿病大鼠肾脏早期损害的保护作用.中国普外基础与临床杂志, 2015, 22(4): 404-411.
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13.	Reaven GM. The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr, 20P <, 25: 391-406.
14.	Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med, 2008, 14(3-4): 222-231.
15.	Rui L, Aguirre V, Kim JK, et al. Insulin/IGF-1 and TNF-alpha stimu-late phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest, 2001, 107(2): 181-189.
16.	Navaneethan SD, Kelly KR, Sabbagh F, et al. Urinary albumin excre-tion, HMW adiponectin, and insulin sensitivity in type 2 diabetic patients undergoing bariatric surgery. Obes Surg, 2010, 20(3): 308-315.
17.	王仕军. 2型糖尿病患者血中瘦素、神经肽Y和肿瘤坏死因子α的变化探析.中国医药指南, 2013, 11(1): 568-569.
18.	Vetter ML, Cardillo S, Rickels MR, et al. Narrative review: effect of bariatric surgery on type 2 diabetes mellitus. Ann Intern Med, 2009, 150(2): 94-103.
19.	Salinari S, Bertuzzi A, Asnaghi S, et al. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care, 2009, 32(3): 375-380.
20.	Whitehead JP, Richards AA, Hickman IJ, et al. Adiponectin-a key adipokine in the metabolic syndrome. Diabetes Obes Metab, 2006, 8(3): 264-280.
21.	卜石, 杨文英, 王昕, 等.长期高脂饲养对大鼠葡萄糖刺激的胰岛素分泌的影响.中华内分泌代谢杂志, 2003, 19(1): 25-28.
22.	Zhang S, Zhang Q, Zhang L, et al. Expression of ghrelin and leptin during the development of type 2 diabetes mellitus in a rat model. Mol Med Rep, 2013, 7(1): 223-228.
23.	Holst JJ, Vilsbøll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol, 2009, 297(1/2): 127-136.
24.	Havel PJ. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes, 2004, 53(suppl 1): S143-S151.
25.	Meirelles K, Ahmed T, Culnan DM, et al. Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat. Ann Surg, 2009, 249(2): 277-285.

1. Whiting DR, Guariguata L, Weil C, et al. IDF diabetes Atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract, 2011, 94(3): 311-321.
2. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a syste-matic review and meta-analysis. JAMA, 2004, 292(14): 1724-1737.
3. 周玉龙, 韩晓东, 狄建忠, 等. Roux-en-Y胃旁路术治疗2型糖尿病的研究进展.中国普外基础与临床杂志, 2014, 21(2): 246-250.
4. 文艺, 冯犁, 张少华, 等. Roux-en-Y胃旁路术对2型糖尿病大鼠肾脏糖异生的影响.基础医学与临床, 2014, 34(5): 661-666.
5. Pories WJ, Macdonald KG, Flickinger EG, et al. Is type II diabetes mellitus(NIDDM) a surgical disease? Ann Surg, 1992, 215(6): 633-643.
6. Yuan M, Konstantopoulos N, Lee J, et al. Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disrup-tion of Ikkbeta. Science, 2001, 293(5535): 1673-1677.
7. 陈若平.减肥手术治疗2型糖尿病的研究进展.中国临床医生, 2014, 42(8): 21-23.
8. Peterli R, Wölnerhanssen B, Peters T, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg, 2009, 250(2): 234-241.
9. Bikman BT, Zheng D, Pories WJ, et al. Mechanism for improved insulin sensitivity after gastric bypass surgery. J Clin Endocrinol Metab, 2008, 93(12): 4656-4663.
10. 王勇, 白洁, 匡立润, 等. Roux-en-Y胃旁路术对GK大鼠骨骼肌组织胰岛素抵抗影响的机制研究.中国普外基础与临床杂志, 2014, 21(2): 162-167.
11. 文艺, 祁巧, 汤礼军, 等. Roux-en-Y胃旁路术对2型糖尿病大鼠肾脏早期损害的保护作用.中国普外基础与临床杂志, 2015, 22(4): 404-411.
12. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature, 2001, 414(6865): 782-787.
13. Reaven GM. The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr, 20P <, 25: 391-406.
14. Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med, 2008, 14(3-4): 222-231.
15. Rui L, Aguirre V, Kim JK, et al. Insulin/IGF-1 and TNF-alpha stimu-late phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest, 2001, 107(2): 181-189.
16. Navaneethan SD, Kelly KR, Sabbagh F, et al. Urinary albumin excre-tion, HMW adiponectin, and insulin sensitivity in type 2 diabetic patients undergoing bariatric surgery. Obes Surg, 2010, 20(3): 308-315.
17. 王仕军. 2型糖尿病患者血中瘦素、神经肽Y和肿瘤坏死因子α的变化探析.中国医药指南, 2013, 11(1): 568-569.
18. Vetter ML, Cardillo S, Rickels MR, et al. Narrative review: effect of bariatric surgery on type 2 diabetes mellitus. Ann Intern Med, 2009, 150(2): 94-103.
19. Salinari S, Bertuzzi A, Asnaghi S, et al. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care, 2009, 32(3): 375-380.
20. Whitehead JP, Richards AA, Hickman IJ, et al. Adiponectin-a key adipokine in the metabolic syndrome. Diabetes Obes Metab, 2006, 8(3): 264-280.
21. 卜石, 杨文英, 王昕, 等.长期高脂饲养对大鼠葡萄糖刺激的胰岛素分泌的影响.中华内分泌代谢杂志, 2003, 19(1): 25-28.
22. Zhang S, Zhang Q, Zhang L, et al. Expression of ghrelin and leptin during the development of type 2 diabetes mellitus in a rat model. Mol Med Rep, 2013, 7(1): 223-228.
23. Holst JJ, Vilsbøll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol, 2009, 297(1/2): 127-136.
24. Havel PJ. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes, 2004, 53(suppl 1): S143-S151.
25. Meirelles K, Ahmed T, Culnan DM, et al. Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat. Ann Surg, 2009, 249(2): 277-285.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Roux-en-Y Gastric Bypass on Expression of Inflammatory Factors and Insulin Receptor Substrate-1/2 in Adipose Tissue of Type 2 Diabetes Mellitus Rats

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