Effect and Mechanism of Gastric Bypass Surgery on Fasting Blood-Glucose in Type 2 Diabetic Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Yuesheng ¹ , SHI Yihua ² , CHEN Fujun. ¹

1.The First Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi 154003, Heilongjiang Province, China;;
2.The Affiliated Wenling Hospital of Wenzhou Medical College, Wenling 317500, Zhejiang Province, China;

Corresponding author：

Keywords：

Type 2 diabetes; Gastric bypass; Dipeptidyl peptidase Ⅳ; Glucagon-like peptide-1

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ObjectiveTo investigate the effect and mechanism of gastric bypass surgery (GBP) on fasting bloo-glucose (FBG) in type 2 diabetic rats. MethodsThe models of type 2 diabetic rats were induced by stretozotocin and 20 diabetic rats were randomly divided into two groups: diabetes-operation group (DO group, n=10) and diabetes-control group (DC group, n=10). Another twenty normal rats were randomly divided into two groups: normaloperation group (NO group, n=10) and normal-control group (NC group, n=10). The rats underwent GBP in DO group and NO group and sham operation in DC group and NC group. The FBG levels, serum dipeptidyl peptidase Ⅳ (DPPⅣ), and glucagon-like peptide-1 (GLP-1) concentrations of rats in each group were detected before operation and at 72 h, on 1 week, 4 weeks, and 8 weeks after operation. ResultsThe FBG levels of rats before operation were not significantly different between DO group and DC group or between NO group and NCgroup (P gt;0.05). After operation, the FBG levels of rats in DO group gradually declined, reached the bottom on 4 weeks after operation and rose slightly on 8 weeks; The FBG levels of rats in DO group were lower after operation than before operation (P lt;0.05); After operation the FBG levels of rats in DO group were higher than that in NO group and NC group at the same time point (P lt;0.05); In DC group, the difference of FBG levels of rats at different time point was not statistically significant (P gt;0.05); The inter-group and intra-group difference of FPG levels of rats for NO group and NC group was not statistically significant (P gt;0.05). The concentrations of serum DPP-Ⅳ of rats before operation were not significantly different in each group (P gt;0.05). After operation, the concentrations of serum DPP-Ⅳ of rats in DO group and NO group gradually decreased and markedly lower than that before operation, respectively (P lt;0.05). The concentrations of serum DPP-Ⅳ of rats after operation in DO group and NO group were significantly lower than that at the same time point in DC group and NC group, respectively (P lt;0.05); The intragroup difference of serum DPP-Ⅳ concentrations of rats for DC group and NC group was not statistically significant (P gt;0.05). The concentrations of serum GLP-1 of rats before operation were not significantly different between DO group and DC group or between NO group and NC group (P gt;0.05). After operation, the concentrations of serum GLP-1 of rats in DO group and NO group gradually increased, reached the top on 4 weeks after operation and declined slightly on 8 weeks; The concentrations of serum GLP-1 of rats in DO group and NO group were higher after operation than before operation (P lt;0.05);After operation, the concentrations of serum GLP-1 of rats in NO group were higher than that in NC group (P lt;0.05), but the concentrations of serum GLP-1 of rats at different time point in NO group were not different (P gt;0.05). The intragroup difference of serum GLP-1 concentrations of rats for DC group and NC group was not statistically significant (P gt;0.05). ConclusionsThere is obvious hypoglycemic effect of GBP on FBG levels of type 2 diabetic rats other than normal rats, in which high secretion of GLP-1 and low secretion of DPP-Ⅳ may be play an important role.

Citation： WANG Yuesheng,SHI Yihua,CHEN Fujun.. Effect and Mechanism of Gastric Bypass Surgery on Fasting Blood-Glucose in Type 2 Diabetic Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(8): 849-853. doi: Copy

1.	Brolin RE. Bariatric surgery and longterm control of morbid obesity [J]. JAMA, 2002, 288(22): 27932796.
2.	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 [J]. Ann Surg, 1995, 222(3): 339352.
3.	Rubino F, Marescaux J. Effect of duodenaljejunal exclusion in a nonobese animal model of type 2 diabetes: a new perspective for an old disease [J]. Ann Surg, 2004, 239(1): 111.
4.	Vetter ML, Cardillo S, Rickels MR, et al. Narrative review: effect of bariatric surgery on type 2 diabetes mellitus [J]. Ann Intern Med, 2009， 150(2): 94103.
5.	Wang X, Zhang S, Chen Y, et al. APM1 gene variants 1377C/G and 4545G/C are associated respectively with obesity and with nonobesity in Chinese type 2 diabetes [J]. Diabetes Res Clin Pract, 2009, 84(3): 205210.
6.	Patriti A, Facchiano E, Sanna A, et al. The enteroinsular axis and the recovery from type 2 diabetes after bariatric surgery [J]. Obes Surg, 2004, 14(6): 840841.
7.	Szkudelski J. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas [J]. Physiol Res, 2001, 50(6): 537546.
8.	Koyama M, Wada R, Sakuraba H, et al. Accelerated loss of islet beta cells in sucrosefed GotoKakizaki rats, a genetic model of noninsulindependent diabetes mellitus [J]. Am J Pathol, 1998, 153(2): 537545.
9.	Greenway SE, Greenway FL 3rd， Klein S. Effects of obesity surgery on noninsulindependent diabetes mellitus [J]. Arch Surg, 2002, 137(10): 11091117.
10.	戴露倢, 王瑜, 王烈, 等. 胃转流术对代谢综合征改善作用的研究进展 [J]. 中国普外基础与临床杂志, 2011, 18(2): 216219.
11.	Ramos AC, Galvo Neto MP, de Souza YM, et al. Laparoscopic duodenaljejunal exclusion in the treatment of type 2 diabetes mellitus in patients with BMI<30 kg/m2 (LBMI) [J]. Obes Surg， 2009, 19(3): 307312.
12.	Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion [J]. World J Surg, 1998, 22(9): 936946.
13.	Ali MR, Fuller WD, Rasmussen J. Detailed description of early response of metabolic syndrome after laparoscopic RouxenY gastric bypass [J]. Surg Obes Relat Dis, 2009, 5(3): 346351.
14.	邓治洲, 王烈, 林忆阳, 等. 胃转流术对非肥胖型2型糖尿病的疗效观察及其对胰高血糖样肽1的影响 [J]. 中国普外基础与临床杂志, 2009, 244(9): 466469.
15.	Bose M, Oliván B, Teixeira J, et al. Do Incretins play a role in the remission of type 2 diabetes after gastric bypass surgery: What are the evidence? [J]. Obes Surg, 2009, 19(2): 217229.
16.	张立宏, 王莉莉, 李松. 二肽基肽酶Ⅳ抑制剂药理学作用及机制的研究进展 [J]. 中国新药杂志, 2009, 18(11): 132134.
17.	Degn KB, Juhl CB, Sturis J, et al. One week’s treatment with the longacting glucagonlike peptide 1 derivative liraglutide (NN2211) markedly improves 24 h glycemia and alpha and betacell function and reduces endogenous glucose release in patients with type 2 diabetes [J]. Diabetes, 2004, 53(5): 11871194.
18.	Behme MT, Dupré J, McDonald TJ. Glucagonlike peptide 1 improved glycemic control in type 1 diabetes [J]. BMC Endocr Disord, 2003, 3(1): 3.
19.	Rao MN, Mulligan K, Tai V, et al. Effects of insulinlike growth factor (IGF)I/IGFbinding protein3 treatment on glucose metabolism and fat distribution in human immunodeficiency virusinfected patients with abdominal obesity and insulin resistance [J]. J Clin Endocrinol Metab, 2010, 95(9): 43614366.
20.	Vilsbll T, Zdravkovic M, LeThi T, et al. Liraglutide, a longacting human glucagonlike peptide1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes [J]. Diabetes Care, 2007, 30(6): 16081610.
21.	MacDonald PE, EIKHoly W, Riedel MJ, et al. The multiple actions of GLP1 on the process of glucosestimulated insulin secretion [J]. Diabetes, 2002, 51 Suppl 3: S434S442.
22.	Drucker DJ, Nauck MA. The incretin system: glucagonlike peptide1 receptor agonists and dipeptidyl peptidase4 inhibitors in type 2 diabetes [J]. Lancet, 2006, 368(9548): 16961705.
23.	Drucker DJ. Dipeptidyl peptidase4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action [J]. Diabetes Care, 2007, 30(6): 13351343.
24.	Mentlein R. Dipeptidylpeptidase Ⅳ (CD26)—role in the inactivation of regulatory peptides [J]. Regul Pept, 1999, 85(1): 924.
25.	Laferrère B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month after RouxenY gastric bypass surgery in obese patients with type 2 diabetes [J]. Diabetes Care, 2007, 30(7): 17091716.
26.	Stearns AT, Balakrishnan A, Tavakkolizadeh A. Impact of RouxenY gastric bypass surgery on rat intestinal glucose transport [J]. Am J Physiol Gastrointest Liver Physiol, 2009, 297(5): G950G957.
27.	Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and metaanalysis [J]. Am J Med, 2009, 122(3): 248256.

1. Brolin RE. Bariatric surgery and longterm control of morbid obesity [J]. JAMA, 2002, 288(22): 27932796.
2. 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 [J]. Ann Surg, 1995, 222(3): 339352.
3. Rubino F, Marescaux J. Effect of duodenaljejunal exclusion in a nonobese animal model of type 2 diabetes: a new perspective for an old disease [J]. Ann Surg, 2004, 239(1): 111.
4. Vetter ML, Cardillo S, Rickels MR, et al. Narrative review: effect of bariatric surgery on type 2 diabetes mellitus [J]. Ann Intern Med, 2009， 150(2): 94103.
5. Wang X, Zhang S, Chen Y, et al. APM1 gene variants 1377C/G and 4545G/C are associated respectively with obesity and with nonobesity in Chinese type 2 diabetes [J]. Diabetes Res Clin Pract, 2009, 84(3): 205210.
6. Patriti A, Facchiano E, Sanna A, et al. The enteroinsular axis and the recovery from type 2 diabetes after bariatric surgery [J]. Obes Surg, 2004, 14(6): 840841.
7. Szkudelski J. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas [J]. Physiol Res, 2001, 50(6): 537546.
8. Koyama M, Wada R, Sakuraba H, et al. Accelerated loss of islet beta cells in sucrosefed GotoKakizaki rats, a genetic model of noninsulindependent diabetes mellitus [J]. Am J Pathol, 1998, 153(2): 537545.
9. Greenway SE, Greenway FL 3rd， Klein S. Effects of obesity surgery on noninsulindependent diabetes mellitus [J]. Arch Surg, 2002, 137(10): 11091117.
10. 戴露倢, 王瑜, 王烈, 等. 胃转流术对代谢综合征改善作用的研究进展 [J]. 中国普外基础与临床杂志, 2011, 18(2): 216219.
11. Ramos AC, Galvo Neto MP, de Souza YM, et al. Laparoscopic duodenaljejunal exclusion in the treatment of type 2 diabetes mellitus in patients with BMI<30 kg/m2 (LBMI) [J]. Obes Surg， 2009, 19(3): 307312.
12. Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion [J]. World J Surg, 1998, 22(9): 936946.
13. Ali MR, Fuller WD, Rasmussen J. Detailed description of early response of metabolic syndrome after laparoscopic RouxenY gastric bypass [J]. Surg Obes Relat Dis, 2009, 5(3): 346351.
14. 邓治洲, 王烈, 林忆阳, 等. 胃转流术对非肥胖型2型糖尿病的疗效观察及其对胰高血糖样肽1的影响 [J]. 中国普外基础与临床杂志, 2009, 244(9): 466469.
15. Bose M, Oliván B, Teixeira J, et al. Do Incretins play a role in the remission of type 2 diabetes after gastric bypass surgery: What are the evidence? [J]. Obes Surg, 2009, 19(2): 217229.
16. 张立宏, 王莉莉, 李松. 二肽基肽酶Ⅳ抑制剂药理学作用及机制的研究进展 [J]. 中国新药杂志, 2009, 18(11): 132134.
17. Degn KB, Juhl CB, Sturis J, et al. One week’s treatment with the longacting glucagonlike peptide 1 derivative liraglutide (NN2211) markedly improves 24 h glycemia and alpha and betacell function and reduces endogenous glucose release in patients with type 2 diabetes [J]. Diabetes, 2004, 53(5): 11871194.
18. Behme MT, Dupré J, McDonald TJ. Glucagonlike peptide 1 improved glycemic control in type 1 diabetes [J]. BMC Endocr Disord, 2003, 3(1): 3.
19. Rao MN, Mulligan K, Tai V, et al. Effects of insulinlike growth factor (IGF)I/IGFbinding protein3 treatment on glucose metabolism and fat distribution in human immunodeficiency virusinfected patients with abdominal obesity and insulin resistance [J]. J Clin Endocrinol Metab, 2010, 95(9): 43614366.
20. Vilsbll T, Zdravkovic M, LeThi T, et al. Liraglutide, a longacting human glucagonlike peptide1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes [J]. Diabetes Care, 2007, 30(6): 16081610.
21. MacDonald PE, EIKHoly W, Riedel MJ, et al. The multiple actions of GLP1 on the process of glucosestimulated insulin secretion [J]. Diabetes, 2002, 51 Suppl 3: S434S442.
22. Drucker DJ, Nauck MA. The incretin system: glucagonlike peptide1 receptor agonists and dipeptidyl peptidase4 inhibitors in type 2 diabetes [J]. Lancet, 2006, 368(9548): 16961705.
23. Drucker DJ. Dipeptidyl peptidase4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action [J]. Diabetes Care, 2007, 30(6): 13351343.
24. Mentlein R. Dipeptidylpeptidase Ⅳ (CD26)—role in the inactivation of regulatory peptides [J]. Regul Pept, 1999, 85(1): 924.
25. Laferrère B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month after RouxenY gastric bypass surgery in obese patients with type 2 diabetes [J]. Diabetes Care, 2007, 30(7): 17091716.
26. Stearns AT, Balakrishnan A, Tavakkolizadeh A. Impact of RouxenY gastric bypass surgery on rat intestinal glucose transport [J]. Am J Physiol Gastrointest Liver Physiol, 2009, 297(5): G950G957.
27. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and metaanalysis [J]. Am J Med, 2009, 122(3): 248256.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect and Mechanism of Gastric Bypass Surgery on Fasting Blood-Glucose in Type 2 Diabetic Rats

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