Influence on Expressions of Insulin Receptor Substrate 1 and Ubiquitin-Protein in Skeletal Muscle of Non-Obese Rats with Type 2 Diabetes Mellitus Following Gastric Bypass Operation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 GONGShuai ¹ ,  RENZe-qiang ¹ , ZHANGPeng-bo ¹ , YAODan ¹ , LIULi ² , WANGJi-ke ² , SUNTing ²

1. Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China;
2. Graduate School of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China;

Corresponding author：

RENZe-qiang, Email: rzq0805@163.com

Keywords：

Gastric bypass operation; Type 2 diabetes mellitus; Insulin receptor substrate 1; Ubiquitin-protein; Insuin resistance

DOI：

10.7507/1007-9424.20160241

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To 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. Methods Male 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. Results ① 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). Conclusions Expression 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.

Citation： GONGShuai, RENZe-qiang, ZHANGPeng-bo, YAODan, LIULi, WANGJi-ke, SUNTing. Influence on Expressions of Insulin Receptor Substrate 1 and Ubiquitin-Protein in Skeletal Muscle of Non-Obese Rats with Type 2 Diabetes Mellitus Following Gastric Bypass Operation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(8): 915-921. doi: 10.7507/1007-9424.20160241 Copy

1.	Pories WJ, Swanson MS, Macdonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg, 1995, 222(3):339-350.
2.	Rubino F. Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis. Diabetes Care, 2008, 31(12):290-296.
3.	Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med, 2004, 351(26):2683-2693.
4.	Alexandrides TK, Skroubis G, Kalfarentzos F. Resolution of diabetes mellitus and metabolic syndrome following Roux-en-Y gastric bypass and a variant of biliopancreatic diversion in patients with morbid obesity. Obes Surg, 2007, 17(2):176-184.
5.	Meneghini LF. Impact of bariatric surgery on type 2 diabetes. Cell Biochem Biophys, 2007, 48(2-3):97-102.
6.	Rubino F, Kaplan LM, Schauer PR, et al. The Diabetes Surgery Summit consensus conference:recommendations for the evaluation and use of gastrointestinal surgery to treat. Ann Surg, 2010, 251(3):399-405.
7.	温雨晴, 谭迎春, 张蓬波, 等.胃转流术对2型糖尿病大鼠脂肪组织胰岛素抵抗的影响.中华实验外科杂志, 2013, 30(10):2324-2326.
8.	张蓬波, 陈守坤, 张秀忠, 等.胃转流术对2型糖尿病大鼠肝组织胰岛素底物-2、葡萄糖转运体-2表达的影响.中华实验外科杂志, 2013, 30(12):2587-2589.
9.	Goto Y, Kakizaki M. The spontaneous-diabetes rat:a model of noninsulin dependent diabetes mellius. Proc Jpn Acad B, 1981, 57(10):381-384.
10.	Portha B. Programmed disorders of beta-cell development and function as one cause for type 2 diabetes? The GK rat paradigm. Diabetes Metab Res Rev, 2005, 21(6):495-504.
11.	Simon A. Gastrointestinal surgery and gut hormones. Curr Opin Endocrinol Diabetes, 2005, 12(1):89-98.
12.	Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med, 2012, 366 (17):1567-1576.
13.	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.
14.	Shao J, Yamashita H, Qiao L, et al. Decreased Akt kinase activity and insulin resistance in C57BL/KsJ-Leprdb/db mice. J Endocrinol, 2000, 167(1):107-115.
15.	Cusi K, Maezono K, Osman A, et al. Insulin resistance differentially affects the PI3-kinase-and MAP kinase-mediated signaling in human muscle. J Clin Invest, 2000, 105(3):311-320.
16.	Biddinger SB, Kahn CR. From mice to men:insights into the insulin resistance syndromes. Annu Rev Physiol, 2006, 68:123-158.
17.	Li SQ, Zhou Y, Wang Y, et al. Upregulation of IRS-1 expression in Goto-Kakizaki rats following Roux-en-Y gastric bypass surgery:resolution of type 2 diabetes? Tohoku J Exp Med, 2011, 225(3):179-186.
18.	Wang X, Hu Z, Hu J, et al. Insulin resistance accelerates muscle protein degradation:Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology, 2006, 147(9):4160-4168.
19.	Goldberg AL. Nobel committee tags ubiquitin for distinction. Neuron, 2005, 45(3):339-344.
20.	Goodyear LJ, Giorgino F, Sherman LA, et al. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J Clin Invest, 1995, 95(5):2195-2204.
21.	Caro JF, Ittoop O, Pories WJ, et al. Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity. J Clin Invest, 1986, 78(1):249-258.
22.	Xu X, Sarikas A, Dias-Santagata DC, et al. The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation. Mol Cell, 2008, 30(4):403-414.
23.	Rome S, Meugnier E, Vidal H. The ubiquitin-proteasome pathway is a new partner for the control of insulin signaling. Curr Opin Clin Nutr Metab Care, 2004, 7(3):249-254.
24.	Balasubramanyam M, Sampathkumar R, Mohan V. Is insulin signaling molecules misguided in diabetes for ubiquitin-proteasome mediated degradation? Mol Cell Biochem, 2005, 275(1-2):117-125.
25.	Song R, Peng W, Zhang Y, et al. Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders. Nature, 2013, 494(7437):375-379.

1. Pories WJ, Swanson MS, Macdonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg, 1995, 222(3):339-350.
2. Rubino F. Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis. Diabetes Care, 2008, 31(12):290-296.
3. Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med, 2004, 351(26):2683-2693.
4. Alexandrides TK, Skroubis G, Kalfarentzos F. Resolution of diabetes mellitus and metabolic syndrome following Roux-en-Y gastric bypass and a variant of biliopancreatic diversion in patients with morbid obesity. Obes Surg, 2007, 17(2):176-184.
5. Meneghini LF. Impact of bariatric surgery on type 2 diabetes. Cell Biochem Biophys, 2007, 48(2-3):97-102.
6. Rubino F, Kaplan LM, Schauer PR, et al. The Diabetes Surgery Summit consensus conference:recommendations for the evaluation and use of gastrointestinal surgery to treat. Ann Surg, 2010, 251(3):399-405.
7. 温雨晴, 谭迎春, 张蓬波, 等.胃转流术对2型糖尿病大鼠脂肪组织胰岛素抵抗的影响.中华实验外科杂志, 2013, 30(10):2324-2326.
8. 张蓬波, 陈守坤, 张秀忠, 等.胃转流术对2型糖尿病大鼠肝组织胰岛素底物-2、葡萄糖转运体-2表达的影响.中华实验外科杂志, 2013, 30(12):2587-2589.
9. Goto Y, Kakizaki M. The spontaneous-diabetes rat:a model of noninsulin dependent diabetes mellius. Proc Jpn Acad B, 1981, 57(10):381-384.
10. Portha B. Programmed disorders of beta-cell development and function as one cause for type 2 diabetes? The GK rat paradigm. Diabetes Metab Res Rev, 2005, 21(6):495-504.
11. Simon A. Gastrointestinal surgery and gut hormones. Curr Opin Endocrinol Diabetes, 2005, 12(1):89-98.
12. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med, 2012, 366 (17):1567-1576.
13. 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.
14. Shao J, Yamashita H, Qiao L, et al. Decreased Akt kinase activity and insulin resistance in C57BL/KsJ-Leprdb/db mice. J Endocrinol, 2000, 167(1):107-115.
15. Cusi K, Maezono K, Osman A, et al. Insulin resistance differentially affects the PI3-kinase-and MAP kinase-mediated signaling in human muscle. J Clin Invest, 2000, 105(3):311-320.
16. Biddinger SB, Kahn CR. From mice to men:insights into the insulin resistance syndromes. Annu Rev Physiol, 2006, 68:123-158.
17. Li SQ, Zhou Y, Wang Y, et al. Upregulation of IRS-1 expression in Goto-Kakizaki rats following Roux-en-Y gastric bypass surgery:resolution of type 2 diabetes? Tohoku J Exp Med, 2011, 225(3):179-186.
18. Wang X, Hu Z, Hu J, et al. Insulin resistance accelerates muscle protein degradation:Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology, 2006, 147(9):4160-4168.
19. Goldberg AL. Nobel committee tags ubiquitin for distinction. Neuron, 2005, 45(3):339-344.
20. Goodyear LJ, Giorgino F, Sherman LA, et al. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J Clin Invest, 1995, 95(5):2195-2204.
21. Caro JF, Ittoop O, Pories WJ, et al. Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity. J Clin Invest, 1986, 78(1):249-258.
22. Xu X, Sarikas A, Dias-Santagata DC, et al. The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation. Mol Cell, 2008, 30(4):403-414.
23. Rome S, Meugnier E, Vidal H. The ubiquitin-proteasome pathway is a new partner for the control of insulin signaling. Curr Opin Clin Nutr Metab Care, 2004, 7(3):249-254.
24. Balasubramanyam M, Sampathkumar R, Mohan V. Is insulin signaling molecules misguided in diabetes for ubiquitin-proteasome mediated degradation? Mol Cell Biochem, 2005, 275(1-2):117-125.
25. Song R, Peng W, Zhang Y, et al. Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders. Nature, 2013, 494(7437):375-379.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Influence on Expressions of Insulin Receptor Substrate 1 and Ubiquitin-Protein in Skeletal Muscle of Non-Obese Rats with Type 2 Diabetes Mellitus Following Gastric Bypass Operation

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content