Mechanism of Roux-en-Y Gastric Bypass Surgery in Improving Skeletal Muscles Insulin Resistance of GK Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WANGYong , BAIJie , KUANGLi-run ,  LIUJin-gang

Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China;

Corresponding author：

LIUJin-gang, Email: liujg@sj-hospital.org

Keywords：

Skeletal muscles insulin resistance; Roux-en-Y gastric bypass surgery; Ghrelin; PI3K-Akt/PKB passway

DOI：

10.7507/1007-9424.20140037

Video：

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Objective To investigate the possible mechanism of the improvement of type 2 diabetes mellitus with insulin resistance of skeletal muscles after Roux-en-Y gastric bypass surgery (RYGB). Methods Thirty GK rats were randomly divided into GK-RYGB group, sham operation group (GK-SO group), and control group (GK-control group); in addition, 10 Wistar rats served as normal control group.On day 28, the animals were sacrificed.The ghrelin concen-tration and PI3Kp85α, Akt/PKB, and GLUT4 levels were measured by ELISA, Western blot, and real-time PCR me-thods, respectively. Results ①Compared with the GK-SO group and GK-control group, the plasma ghrelin levels were significantly increased in the normal control group (P < 0.01) and GK-RYGB group (P < 0.01).②Compared with the GK-SO group and GK-control group, p-/t-PI3Kp85α, p-/t-Akt/PKB, and m-/t-GLUT4 proteins were significantly incre-ased in the normal control group (P < 0.01, P < 0.05, and P < 0.01, respectively) and GK-RYGB group (P < 0.01, P < 0.05, and P < 0.01, respectively).③Compared with the GK-SO group and GK-control group, PI3Kp85α, Akt, and GLUT4 mRNA were significantly increased in the normal control group (P < 0.01, P < 0.05, and P < 0.05, respectively) and GK-RYGB group (P < 0.01, P < 0.05, and P < 0.05, respectively). Conclusion RYGB could elevate the ghrelin level obviously and upregulate PI3Kp85α, Akt/PKB, and GLUT4 levels and thus improve the insulin resistance of skeletal muscles of rats with T2DM.

Citation： WANGYong, BAIJie, KUANGLi-run, LIUJin-gang. Mechanism of Roux-en-Y Gastric Bypass Surgery in Improving Skeletal Muscles Insulin Resistance of GK Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(2): 162-167. doi: 10.7507/1007-9424.20140037 Copy

1.	Danaei G, Finucane MM, Lu Y, et al.National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980:systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants[J].Lancet, 2011, 378(9785):31-40.
2.	Lazar MA.How obesity causes diabetes:not a tall tale[J].Science, 2005, 307(5708):373-375.
3.	Picot J, Jones J, Colquitt JL, et al.The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity:a systematic review and economic evaluation[J].Health Technol Assess, 2009, 13(41):1-190, 215.
4.	Liu Y, Zhou Y, Wang Y, et al.Roux-en-Y gastric bypass-induced improvement of glucose tolerance and insulin resistance in type 2 diabetic rats are mediated by glucagon-like peptide-1[J].Obes Surg, 2011, 21(9):1424-1431.
5.	Buchwald H, Estok R, Fahrbach K, et al.Weight and type 2 diabetes after bariatric surgery:systematic review and meta-anal-ysis[J].Am J Med, 2009, 122(3):248-256.e5.
6.	Kashyap SR, Daud S, Kelly KR, et al.Acute effects of gastric bypass versus gastric restrictive surgery onβ-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes[J].Int J Obes, 2010, 34(3):462-471.
7.	Cummings DE, Overduin J, Shannon MH, et al.Hormonal mechanisms of weight loss and diabetes resolution after bariatric surgery[J].Surg Obes Relat Dis, 2005, 1(3):358-368.
8.	Cummings DE, Weigle DS, Frayo RS, et al.Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery[J].N Engl J Med, 2002, 346(21):1623-1630.
9.	Gauna C, Meyler FM, Janssen JA, et al.Administration of acyl-ated ghrelin reduces insulin sensitivity, whereas the combinationof acylated plus unacylated ghrelin strongly improves insulin sensi-tivity[J].J Clin Endocrinol Metab, 2004, 89(10):5035-5042.
10.	Faria G, Preto J, da Costa EL, et al.Acute improvement in insulin resistance after laparoscopic Roux-en-Y gastric bypass:is 3 days enough to correct insulin metabolism?[J].Obes Surg, 2013, 23(1):103-110.
11.	Chai F, Wang Y, Zhou Y, et al.Adiponectin downregulates hy-perglycemia and reduces pancreatic islet apoptosis after Roux-en-Y gastric bypass surgery[J].Obes Surg, 2011, 21(6):768-773.
12.	Durczynski A, Szymanski D, Nowicki M, et al.The impact of the repair of staple line dehiscence in post-RYGB patients on glucose homeostasis and gut hormones-a preliminary study[J].Endokrynol Pol, 2013, 64(1):7-12.
13.	Sjöström L, Narbro K, Sjöström CD, et al.Effects of bariatric surgery on mortality in Swedish obese subjects[J].N Engl J Med, 2007, 357(8):741-752.
14.	Cummings DE, Purnell JQ, Frayo RS, et al.A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans[J].Diabetes, 2001, 50(8):1714-1719.
15.	Ariyasu H, Takaya K, Iwakura H, et al.Transgenic mice overex-pressing des-acyl ghrelin show small phenotype[J].Endocrino-logy, 2005, 146(1):355-364.
16.	Sun Y, Butte NF, Garcia JM, et al.Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance[J].Endocrinology, 2008, 149(2):843-850.
17.	Fung JN, Jeffery PL, Lee JD, et al.Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo[J].Am J Physiol Endocrinol Metab, 2013, 305(2):E305-E313.
18.	Cheyuo C, Jacob A, Wang P.Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis[J].Am J Physiol Endocrinol Metab, 2012, 302(3):E265-E272.
19.	Vila G, Maier C, Riedl M, et al.Bacterial endotoxin induces biphasic changes in plasma ghrelin in healthy humans[J].J Clin Endocrinol Metab, 2007, 92(10):3930-3934.
20.	Delgado M, Ganea D.Anti-inflammatory neuropeptides:a new class of endogenous immunoregulatory agents[J].Brain Behav Immun, 2008, 22(8):1146-1151.
21.	Dixit VD, Schaffer EM, Pyle RS, et al.Ghrelin inhibits leptin-and activation-induced proinflammatory cytokine expression by human monocytes and T cells[J].J Clin Invest, 2004, 114(1):57-66.
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[J].Mol Med Rep, 2013, 7(1):223-228.
23.	Cusi K, Maezono K, Osman A, et al.Insulin resistance differentially affects the PI3-kinase-and MAP kinase-mediated signaling in human muscle[J].J Clin Invest, 2000, 105(3):311-320.
24.	Cantley LC.The phosphoinositide 3-kinase pathway[J].Science, 2002, 296(5573):1655-1657.
25.	Zierath JR, Krook A, Wallberg-Henriksson H.Insulin action in skeletal muscle from patients with NIDDM[J].Mol Cell Biochem, 1998, 182(1-2):153-160.

1. Danaei G, Finucane MM, Lu Y, et al.National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980:systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants[J].Lancet, 2011, 378(9785):31-40.
2. Lazar MA.How obesity causes diabetes:not a tall tale[J].Science, 2005, 307(5708):373-375.
3. Picot J, Jones J, Colquitt JL, et al.The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity:a systematic review and economic evaluation[J].Health Technol Assess, 2009, 13(41):1-190, 215.
4. Liu Y, Zhou Y, Wang Y, et al.Roux-en-Y gastric bypass-induced improvement of glucose tolerance and insulin resistance in type 2 diabetic rats are mediated by glucagon-like peptide-1[J].Obes Surg, 2011, 21(9):1424-1431.
5. Buchwald H, Estok R, Fahrbach K, et al.Weight and type 2 diabetes after bariatric surgery:systematic review and meta-anal-ysis[J].Am J Med, 2009, 122(3):248-256.e5.
6. Kashyap SR, Daud S, Kelly KR, et al.Acute effects of gastric bypass versus gastric restrictive surgery onβ-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes[J].Int J Obes, 2010, 34(3):462-471.
7. Cummings DE, Overduin J, Shannon MH, et al.Hormonal mechanisms of weight loss and diabetes resolution after bariatric surgery[J].Surg Obes Relat Dis, 2005, 1(3):358-368.
8. Cummings DE, Weigle DS, Frayo RS, et al.Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery[J].N Engl J Med, 2002, 346(21):1623-1630.
9. Gauna C, Meyler FM, Janssen JA, et al.Administration of acyl-ated ghrelin reduces insulin sensitivity, whereas the combinationof acylated plus unacylated ghrelin strongly improves insulin sensi-tivity[J].J Clin Endocrinol Metab, 2004, 89(10):5035-5042.
10. Faria G, Preto J, da Costa EL, et al.Acute improvement in insulin resistance after laparoscopic Roux-en-Y gastric bypass:is 3 days enough to correct insulin metabolism?[J].Obes Surg, 2013, 23(1):103-110.
11. Chai F, Wang Y, Zhou Y, et al.Adiponectin downregulates hy-perglycemia and reduces pancreatic islet apoptosis after Roux-en-Y gastric bypass surgery[J].Obes Surg, 2011, 21(6):768-773.
12. Durczynski A, Szymanski D, Nowicki M, et al.The impact of the repair of staple line dehiscence in post-RYGB patients on glucose homeostasis and gut hormones-a preliminary study[J].Endokrynol Pol, 2013, 64(1):7-12.
13. Sjöström L, Narbro K, Sjöström CD, et al.Effects of bariatric surgery on mortality in Swedish obese subjects[J].N Engl J Med, 2007, 357(8):741-752.
14. Cummings DE, Purnell JQ, Frayo RS, et al.A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans[J].Diabetes, 2001, 50(8):1714-1719.
15. Ariyasu H, Takaya K, Iwakura H, et al.Transgenic mice overex-pressing des-acyl ghrelin show small phenotype[J].Endocrino-logy, 2005, 146(1):355-364.
16. Sun Y, Butte NF, Garcia JM, et al.Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance[J].Endocrinology, 2008, 149(2):843-850.
17. Fung JN, Jeffery PL, Lee JD, et al.Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo[J].Am J Physiol Endocrinol Metab, 2013, 305(2):E305-E313.
18. Cheyuo C, Jacob A, Wang P.Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis[J].Am J Physiol Endocrinol Metab, 2012, 302(3):E265-E272.
19. Vila G, Maier C, Riedl M, et al.Bacterial endotoxin induces biphasic changes in plasma ghrelin in healthy humans[J].J Clin Endocrinol Metab, 2007, 92(10):3930-3934.
20. Delgado M, Ganea D.Anti-inflammatory neuropeptides:a new class of endogenous immunoregulatory agents[J].Brain Behav Immun, 2008, 22(8):1146-1151.
21. Dixit VD, Schaffer EM, Pyle RS, et al.Ghrelin inhibits leptin-and activation-induced proinflammatory cytokine expression by human monocytes and T cells[J].J Clin Invest, 2004, 114(1):57-66.
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[J].Mol Med Rep, 2013, 7(1):223-228.
23. Cusi K, Maezono K, Osman A, et al.Insulin resistance differentially affects the PI3-kinase-and MAP kinase-mediated signaling in human muscle[J].J Clin Invest, 2000, 105(3):311-320.
24. Cantley LC.The phosphoinositide 3-kinase pathway[J].Science, 2002, 296(5573):1655-1657.
25. Zierath JR, Krook A, Wallberg-Henriksson H.Insulin action in skeletal muscle from patients with NIDDM[J].Mol Cell Biochem, 1998, 182(1-2):153-160.

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Mechanism of Roux-en-Y Gastric Bypass Surgery in Improving Skeletal Muscles Insulin Resistance of GK Rats

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