Influence of Sleeve Gastrectomy on Blood Glucose, Ghrelin, and Glucagon Like Peptide-1 Levels in GK Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Zhanyong , YAN Lingling , WU Dan , LUO Xiao , WU Yiping.

Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China;

Corresponding author：

Keywords：

Sleeve gastrectomy; Goto-kakizaki rat; Growth hormone releasing peptide ghrelin; Glucagon like peptide-1

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ObjectiveTo investigate the effect and mechanism of sleeve gastrectomy (SG) on reducing blood glucose level. MethodsThirty GK rats were randomly divided into SG group, sham operation (SO) group, pair-fed (PF) group, and blank control (BC) group. The changes of weight, fasting blood glucose, glucose tolerance (oral glucose tolerance test, OGTT), insulin tolerance (insulin tolerance test, ITT), plasma insulin, ghrelin, and glucagon like peptide-1 (GLP-1) were monitored before and 24 weeks after operation respectively. ResultsFrom the 4th week after operation, weight gain in SG group and PF group began to decrease significantly compared with SO group (P lt;0.01). From the 2nd week after operation, fasting blood glucose level in SG group was lower than that in SO, PF, and BC groups (P lt;005), and the glucose tolerance in SG group obviously improved compared with preoperation and the other 3 groups (P lt;0.01). On the 6th week after operation, the insulin sensitivity in SG group obviously improved compared with SO group (P lt;0.05, P lt;0.01). There was no significant difference of insulin level between SG group and SO group (P gt;0.05), ghrelin level significantly decreased (P lt;0.01) while GLP-1 level significantly increased (P lt;0.01) in SG group compared with SO group during 2-24 weeks after operation. ConclusionsThe effect of SG on reducing blood glucose is definite. SG can directly lower blood glucose independent with weight loss. Postoperative decreased ghrelin level and increased GLP-1 level may be its primary mechanism.

Citation： ZHU Zhanyong,YAN Lingling,WU Dan,LUO Xiao,WU Yiping.. Influence of Sleeve Gastrectomy on Blood Glucose, Ghrelin, and Glucagon Like Peptide-1 Levels in GK Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(6): 603-609. doi: Copy

1.	Vidal J, Ibarzabal A, Romero F, et al. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects [J]. Obes Surg, 2008, 18(9): 10771082.
2.	Gumbs AA, Gagner M, Dakin G, et al. Sleeve gastrectomy for morbid obesity [J]. Obes Surg, 2007, 17(7): 962969.
3.	Sammour T, Hill AG, Singh P, et al. Laparoscopic sleeve gastrectomy as a singlestage bariatric procedure [J]. Obes Surg, 2010, 20(3): 271275.
4.	Pruessner JC, Kirschbaum C, Meinlschmid G, et al. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus timedependent change [J]. Psychoneuroendocrinology, 2003, 28(7): 916931.
5.	Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion [J]. World J Surg, 1998, 22(9): 936946.
6.	Moo TA, Rubino F. Gastrointestinal surgery as treatment for type 2 diabetes [J]. Curr Opin Endocrinol Diabetes Obes, 2008, 15(2): 153158.
7.	Pereferrer FS, Gonzàlez MH, Rovira AF, et al. Influence of sleeve gastrectomy on several experimental models of obesity: metabolic and hormonal implications [J]. Obes Surg, 2008, 18(1): 97108.
8.	Schlager A, Khalaileh A, Mintz Y, et al. A mouse model for sleeve gastrectomy: applications for diabetes research [J]. Microsurgery, 2011, 31(1): 6671.
9.	Reavis KM, Hinojosa MW, Smith BR, et al. Singlelaparoscopic incision transabdominal surgery sleeve gastrectomy [J]. Obes Surg, 2008, 18(11): 14921494.
10.	Lee WJ, Ser KH, Chong K, et al. Laparoscopic sleeve gastrectomy for diabetes treatment in nonmorbidly obese patients: efficacy and change of insulin secretion [J]. Surgery, 2010, 147(5): 664669.
11.	GillRandall RJ, Adams D, Ollerton RL, et al. Is human Type 2 diabetes maternally inherited? Insights from an animal model [J]. Diabet Med, 2004, 21(7): 759762.
12.	GillRandall R, Adams D, Ollerton RL, et al. Type 2 diabetes mellitus-genes or intrauterine environment? An embryo transfer paradigm in rats [J]. Diabetologia, 2004, 47(8): 13541359.
13.	de Bona Castelan J, Bettiol J, d’Acampora AJ, et al. Sleeve gastrectomy model in Wistar rats [J]. Obes Surg, 2007, 17(7): 957961.
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素样肽1的影响 [J]. 中国普外基础与临床杂志, 2009, 16(6): 466469.
15.	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848.
16.	Purnell JQ, Flum DR. Bariatric surgery and diabetes: who should be offered the option of remission? [J]. JAMA, 2009, 301(15): 15931595.
17.	Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG, et al. Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery [J]. Diabetes, 2003, 52(5): 10981103.
18.	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.
19.	Rizzello M, Abbatini F, Casella G, et al. Early postoperative insulinresistance changes after sleeve gastrectomy [J]. Obes Surg, 2010, 20(1): 5055.
20.	Cummings DE, Overduin J. Gastrointestinal regulation of food intake [J]. J Clin Invest, 2007, 117(1): 1323.
21.	Cummings DE, Shannon MH. Roles for ghrelin in the regulation of appetite and body weight [J]. Arch Surg, 2003, 138(4): 389396.
22.	Kageyama H, Funahashi H, Hirayama M, et al. Morphological analysis of ghrelin and its receptor distribution in the rat pancreas [J]. Regul Pept, 2005, 126(12): 6771.
23.	Dezaki K, Kakei M, Yada T. Ghrelin uses Galphai2 and activates voltagedependent K+ channels to attenuate glucoseinduced Ca2+ signaling and insulin release in islet betacells: novel signal transduction of ghrelin [J]. Diabetes, 2007, 56(9): 23192327.
24.	Pykk SM, Kellokoski E, Hrkk S, et al. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes [J]. Diabetes, 2003, 52(10): 25462553.
25.	Nslund E, Kral JG. Impact of gastric bypass surgery on gut hormones and glucose homeostasis in type 2 diabetes [J]. Diabetes, 2006, 55(Supplement 2): S92S97.
26.	D’Alessio DA, Vahl TP. Glucagonlike peptide 1: evolution of an incretin into a treatment for diabetes [J]. Am J Physiol Endocrinol Metab, 2004, 286(6): E882E890.
27.	Li Y, Cao X, Li LX, et al. BetaCell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagonlike peptide1 [J]. Diabetes, 2005, 54(2): 482491.
28.	Berthoud HR. Paying the price for eating ice cream: is excessive GLP1 signaling in the brain the culprit? [J]. Endocrinology, 2008, 149(10): 47654767.
29.	Baggio LL, Drucker DJ. Biology of incretins: GLP1 and GIP [J]. Gastroenterology, 2007, 132(6): 21312157.
30.	贾乾斌, 汪静, 赵纪春, 等. 胰升血糖素样肽1对肝切除术后葡萄糖耐量的影响 [J]. 中国普外基础与临床杂志, 2001, 8(4): 215217.
31.	Micic D, Duntas L, Cvijovic G, et al. Ghrelin and the enteroinsular axis in healthy men [J]. Hormones (Athens), 2007, 6(4): 321326.

1. Vidal J, Ibarzabal A, Romero F, et al. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects [J]. Obes Surg, 2008, 18(9): 10771082.
2. Gumbs AA, Gagner M, Dakin G, et al. Sleeve gastrectomy for morbid obesity [J]. Obes Surg, 2007, 17(7): 962969.
3. Sammour T, Hill AG, Singh P, et al. Laparoscopic sleeve gastrectomy as a singlestage bariatric procedure [J]. Obes Surg, 2010, 20(3): 271275.
4. Pruessner JC, Kirschbaum C, Meinlschmid G, et al. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus timedependent change [J]. Psychoneuroendocrinology, 2003, 28(7): 916931.
5. Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion [J]. World J Surg, 1998, 22(9): 936946.
6. Moo TA, Rubino F. Gastrointestinal surgery as treatment for type 2 diabetes [J]. Curr Opin Endocrinol Diabetes Obes, 2008, 15(2): 153158.
7. Pereferrer FS, Gonzàlez MH, Rovira AF, et al. Influence of sleeve gastrectomy on several experimental models of obesity: metabolic and hormonal implications [J]. Obes Surg, 2008, 18(1): 97108.
8. Schlager A, Khalaileh A, Mintz Y, et al. A mouse model for sleeve gastrectomy: applications for diabetes research [J]. Microsurgery, 2011, 31(1): 6671.
9. Reavis KM, Hinojosa MW, Smith BR, et al. Singlelaparoscopic incision transabdominal surgery sleeve gastrectomy [J]. Obes Surg, 2008, 18(11): 14921494.
10. Lee WJ, Ser KH, Chong K, et al. Laparoscopic sleeve gastrectomy for diabetes treatment in nonmorbidly obese patients: efficacy and change of insulin secretion [J]. Surgery, 2010, 147(5): 664669.
11. GillRandall RJ, Adams D, Ollerton RL, et al. Is human Type 2 diabetes maternally inherited? Insights from an animal model [J]. Diabet Med, 2004, 21(7): 759762.
12. GillRandall R, Adams D, Ollerton RL, et al. Type 2 diabetes mellitus-genes or intrauterine environment? An embryo transfer paradigm in rats [J]. Diabetologia, 2004, 47(8): 13541359.
13. de Bona Castelan J, Bettiol J, d’Acampora AJ, et al. Sleeve gastrectomy model in Wistar rats [J]. Obes Surg, 2007, 17(7): 957961.
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素样肽1的影响 [J]. 中国普外基础与临床杂志, 2009, 16(6): 466469.
15. 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848.
16. Purnell JQ, Flum DR. Bariatric surgery and diabetes: who should be offered the option of remission? [J]. JAMA, 2009, 301(15): 15931595.
17. Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG, et al. Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery [J]. Diabetes, 2003, 52(5): 10981103.
18. 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.
19. Rizzello M, Abbatini F, Casella G, et al. Early postoperative insulinresistance changes after sleeve gastrectomy [J]. Obes Surg, 2010, 20(1): 5055.
20. Cummings DE, Overduin J. Gastrointestinal regulation of food intake [J]. J Clin Invest, 2007, 117(1): 1323.
21. Cummings DE, Shannon MH. Roles for ghrelin in the regulation of appetite and body weight [J]. Arch Surg, 2003, 138(4): 389396.
22. Kageyama H, Funahashi H, Hirayama M, et al. Morphological analysis of ghrelin and its receptor distribution in the rat pancreas [J]. Regul Pept, 2005, 126(12): 6771.
23. Dezaki K, Kakei M, Yada T. Ghrelin uses Galphai2 and activates voltagedependent K+ channels to attenuate glucoseinduced Ca2+ signaling and insulin release in islet betacells: novel signal transduction of ghrelin [J]. Diabetes, 2007, 56(9): 23192327.
24. Pykk SM, Kellokoski E, Hrkk S, et al. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes [J]. Diabetes, 2003, 52(10): 25462553.
25. Nslund E, Kral JG. Impact of gastric bypass surgery on gut hormones and glucose homeostasis in type 2 diabetes [J]. Diabetes, 2006, 55(Supplement 2): S92S97.
26. D’Alessio DA, Vahl TP. Glucagonlike peptide 1: evolution of an incretin into a treatment for diabetes [J]. Am J Physiol Endocrinol Metab, 2004, 286(6): E882E890.
27. Li Y, Cao X, Li LX, et al. BetaCell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagonlike peptide1 [J]. Diabetes, 2005, 54(2): 482491.
28. Berthoud HR. Paying the price for eating ice cream: is excessive GLP1 signaling in the brain the culprit? [J]. Endocrinology, 2008, 149(10): 47654767.
29. Baggio LL, Drucker DJ. Biology of incretins: GLP1 and GIP [J]. Gastroenterology, 2007, 132(6): 21312157.
30. 贾乾斌, 汪静, 赵纪春, 等. 胰升血糖素样肽1对肝切除术后葡萄糖耐量的影响 [J]. 中国普外基础与临床杂志, 2001, 8(4): 215217.
31. Micic D, Duntas L, Cvijovic G, et al. Ghrelin and the enteroinsular axis in healthy men [J]. Hormones (Athens), 2007, 6(4): 321326.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Influence of Sleeve Gastrectomy on Blood Glucose, Ghrelin, and Glucagon Like Peptide-1 Levels in GK Rats

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