Sleeve Gastrectomy Provides a Better Control of Diabetes by Decreasing Ghrelin in the Diabetic Goto–Kakizaki Rats

  • Feng Li
  • Guangyong Zhang
  • Jianwei Liang
  • Xiangjiu Ding
  • Zhiqiang Cheng
  • Sanyuan Hu
Original Article



Sleeve gastrectomy (SG) and modified duodenal jejunal bypass (MDJB) were compared as procedures for glucose control. We aim to form the initial conclusions with respect to the possibility of (1) whether gastric fundus exclusion is essential for the control of diabetes and (2) application as a low morbidity procedure.

Materials and Methods

SG and MDJB were performed on 10- to 12-week-old Goto–Kakizaki rats that spontaneously develop type 2 diabetes. Rats were observed for 36 weeks after surgery, and glucose, insulin, glucagons-like peptide-1 (GLP-1), glucose tolerate, insulin sensitivity, cholesterol, triglycerides, and free fatty acid levels were measured.


Apart from distinct weight loss of SG and MDJB after 1 month compared with sham-operated rats (P < 0.001), SG showed strikingly improved blood glucose levels and significantly decreased Ghrelin secretion (P < 0.001). Furthermore, SG resulted in a shorter operative time (P < 0.01) and postoperative recovery time (P < 0.01) than MDJB group.


SG shows better control in terms of glucose tolerance and other measurements. This study provides direct evidence that SG possesses better improvement of diabetes by reduction of Ghrelin.


Sleeve gastrectomy Modified duodenal jejunal bypass Glucagon-like peptide-1 Insulin 



Sleeve gastrectomy




Modified duodenal jejunal bypass


Oral glucose tolerance test


Insulin tolerance test


Glucagon-like peptide-1


  1. 1.
    Papadopoulos AA, Kontodimopoulos N, Frydas A, Ikonomakis E, Niakas D. Predictors of health-related quality of life in type II diabetic patients in Greece. BMC Public Health 2007;7:186.CrossRefPubMedGoogle Scholar
  2. 2.
    King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414–1431.CrossRefPubMedGoogle Scholar
  3. 3.
    Chan BS, Tsang MW, Lee VW, Lee KK. Cost of type 2 diabetes mellitus in Hong Kong Chinese. Int J Clin Pharmacol Ther 2007;45:455–468.PubMedGoogle Scholar
  4. 4.
    Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW, Mohammed BS. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 2004;350:2549–2557.CrossRefPubMedGoogle Scholar
  5. 5.
    Kelley DE. Thermodynamics, liposuction, and metabolism. N Engl J Med 2004;350:2542–2544.CrossRefPubMedGoogle Scholar
  6. 6.
    Kirchner H, Guijarro A, Meguid MM. Is a model useful in exploring the catabolic mechanisms of weight loss after gastric bypass in humans? Curr Opin Clin Nutr Metab Care 2007;10:463–474.CrossRefPubMedGoogle Scholar
  7. 7.
    Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995;222:339–352.CrossRefPubMedGoogle Scholar
  8. 8.
    Detournay B, Cros S, Charbonnel B, Grimaldi A, Liard F, Cogneau J, Fagnani F, Eschwège E. Managing type 2 diabetes in France: the ECODIA survey. Diabetes Metab 2000;26:363–369.PubMedGoogle Scholar
  9. 9.
    Scopinaro N, Adami GF, Marinari GM, Gianetta E, Traverso E, Friedman D, Camerini G, Baschieri G, Simonelli A. Biliopancreatic diversion. World J Surg 1998;22:936–946.CrossRefPubMedGoogle Scholar
  10. 10.
    Pereferrer FS, Gonzàlez MH, Rovira AF, Blasco SB, Rivas AM, del Castillo Déjardin D. Influence of sleeve gastrectomy on several experimental models of obesity: metabolic and hormonal implications. Obes Surg 2008;18(1):97–108.CrossRefPubMedGoogle Scholar
  11. 11.
    Vidal J, Ibarzabal A, Romero F, Delgado S, Momblán D, Flores L, Lacy A. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects. Obes Surg 2008;18(9):1077–1082.CrossRefPubMedGoogle Scholar
  12. 12.
    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. Ann Surg 2004;239:1–11.CrossRefPubMedGoogle Scholar
  13. 13.
    Cohen RV, Schiavon CA, Pinheiro JS, Correa JL, Rubino F. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22–34 kg/m2: a report of 2 cases. Surg Obes Relat Dis 2007;3:195–197.CrossRefPubMedGoogle Scholar
  14. 14.
    Rubino F, Gagner M. Potential of surgery for curing type 2 diabetes mellitus. Ann Surg 2002;236:554–559.CrossRefPubMedGoogle Scholar
  15. 15.
    Cowan GS Jr, Buffington CK. Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery. World J Surg 1998;22:987–992.CrossRefPubMedGoogle Scholar
  16. 16.
    Marceau P, Hould FS, Simard S, Lebel S, Bourque RA, Potvin M, Biron S. Biliopancreatic diversion with duodenal switch. World J Surg 1998;22:947–954.CrossRefPubMedGoogle Scholar
  17. 17.
    Schauer PR, Ikramuddin S, Gourash W, Ramanathan R, Luketich J. Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Ann Surg 2000;232:515–529.CrossRefPubMedGoogle Scholar
  18. 18.
    Wittgrove AC, Clark GW. Laparoscopic gastric bypass, Roux-en-Y-500 patients: technique and results, with 3–60 month follow-up. Obes Surg 2000;10:233–239.CrossRefPubMedGoogle Scholar
  19. 19.
    Pontiroli AE, Pizzocri P, Librenti MC, Vedani P, Marchi M, Cucchi E, Orena C, Paganelli M, Giacomelli M, Ferla G, Folli F. Laparoscopic adjustable gastric banding for the treatment of morbid (grade 3) obesity and its metabolic complications: a three-year study. J Clin Endocrinol Metab 2002;87:3555–3561.CrossRefPubMedGoogle Scholar
  20. 20.
    Scopinaro N, Gianetta E, Adami GF, Friedman D, Traverso E, Marinari GM, Cuneo S, Vitale B, Ballari F, Colombini M, Baschieri G, Bachi V. Biliopancreatic diversion for obesity at eighteen years. Surgery 1996;119:261–268.CrossRefPubMedGoogle Scholar
  21. 21.
    Dixon JB, O’Brien PE. Health outcomes of severely obese type 2 diabetic subjects 1 year after laparoscopic adjustable gastric banding. Diabetes Care 2002;25:358–363.CrossRefPubMedGoogle Scholar
  22. 22.
    Galli J, Li LS, Glaser A, Ostenson CG, Jiao H, Fakhrai-Rad H, Jacob HJ, Lander ES, Luthman H. Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat. Nat Genet 1996;12:31–37.CrossRefPubMedGoogle Scholar
  23. 23.
    Inabnet WB 3rd, Milone L, Korner J, Durak E, Ahmed L, Pomrantz J, Harris PE, Bessler M. A rodent model of metabolic surgery for study of type 2 diabetes and positron emission tomography scanning of beta cell mass. Surg Obes Relat Dis 2009;5(2):212–217.CrossRefPubMedGoogle Scholar
  24. 24.
    National Research Council. Public Health Service Policy and Government Principles regarding the care and use of animals. Appendix D. Guide for the care and use of animals. Washington, DC: National Academy, 1996, pp 116–118.Google Scholar
  25. 25.
    de Bona Castelan J, Bettiol J, d’Acampora AJ, Castelan JV, de Souza JC, Bressiani V, Giroldi SB. Sleeve gastrectomy model in Wistar rats. Obes Surg 2007;17(7):957–961.CrossRefPubMedGoogle Scholar
  26. 26.
    Pories WJ, MacDonald KG Jr, Morgan EJ, Sinha MK, Dohm GL, Swanson MS, Barakat HA, Khazanie PG, Leggett-Frazier N, Long SD. Surgical treatment of obesity and its effect on diabetes: 10-y follow-up. Am J Clin Nutr 1992;55:582S–585S.PubMedGoogle Scholar
  27. 27.
    Patriti A, Aisa MC, Annetti C, Sidoni A, Galli F, Ferri I, Gullà N, Donini A. How the hindgut can cure type 2 diabetes. Ileal transposition improves glucose metabolism and beta-cell function in Goto-kakizaki rats through an enhanced Proglucagon gene expression and L-cell number. Surgery 2007;142:74–85.CrossRefPubMedGoogle Scholar
  28. 28.
    Castagneto M, De Gaetano A, Mingrone G, Tacchino R, Nanni G, Capristo E, Benedetti G, Tataranni PA, Greco AV. Normalization of insulin sensitivity in the obese patient after stable weight reduction with biliopancreatic diversion. Obes Surg 1994;4:161–168.CrossRefPubMedGoogle Scholar
  29. 29.
    MacDonald KG Jr, Long SD, Swanson MS, Brown BM, Morris P, Dohm GL, Pories WJ. The gastric bypass operation reduces the progression and mortality of non-insulin-dependent diabetes mellitus. J Gastrointest Surg 1997;1:213–220. discussion 220.CrossRefPubMedGoogle Scholar
  30. 30.
    Meneghini LF. Impact of bariatric surgery on type 2 diabetes. Cell Biochem Biophys 2007;48:97–102.CrossRefPubMedGoogle Scholar
  31. 31.
    Frezza EE, Wachtel MS, Chiriva-Internati M. The multiple faces of glucagons-like peptide 1-obesity, appetite, and stress: what is next? A review. Dig Dis Sci 2007;52:643–649.CrossRefPubMedGoogle Scholar
  32. 32.
    Langer FB, Reza Hoda MA, Bohdjalian A, Felberbauer FX, Zacherl J, Wenzl E, Schindler K, Luger A, Ludvik B, Prager G. Sleeve gastrectomy and gastric banding: effects on plasma Ghrelin levels. Obes Surg 2005;15:1024–1029.CrossRefPubMedGoogle Scholar
  33. 33.
    Näslund E, Backman L, Holst JJ, Theodorsson E, Hellström PM. Importance of small bowel peptides for the improved glucose metabolism 20 years after jejunoileal bypass for obesity. Obes Surg 1998;8:253–260.CrossRefPubMedGoogle Scholar
  34. 34.
    Brzozowski T, Konturek PC, Drozdowicz D, Konturek SJ, Pawlik M, Sliwowski Z, Pawlik WW, Hahn EG. Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence. Inflammopharmacology 2005;13:45–62.CrossRefPubMedGoogle Scholar
  35. 35.
    Kotidis EV, Koliakos GG, Baltzopoulos VG, Ioannidis KN, Yovos JG, Papavramidis ST. Serum ghrelin, leptin and adiponectin levels before and after weight loss: comparison of three methods of treatment–a prospective study. Obes Surg 2006;16:1425–1432.CrossRefPubMedGoogle Scholar
  36. 36.
    Pusztai P, Sarman B, Ruzicska E, Toke J, Racz K, Somogyi A, Tulassay Z. Ghrelin: a new peptide regulating the neurohormonal system, energy homeostasis and glucose metabolism. Diabetes Metab Res Rev 2008;24:343–352.CrossRefPubMedGoogle Scholar
  37. 37.
    Gentileschi P, Kini S, Catarci M, Gagner M. Evidence-based medicine: open and laparoscopic bariatric surgery. Surg Endosc 2002;16:736–744.CrossRefPubMedGoogle Scholar
  38. 38.
    Schauer PR, Ikramuddin S. Laparoscopic surgery for morbid obesity. Surg Clin North Am 2001;81:1145–1179.CrossRefPubMedGoogle Scholar
  39. 39.
    Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 2002;23:201–229.CrossRefPubMedGoogle Scholar
  40. 40.
    Strader AD, Vahl TP, Jandacek RJ, Woods SC, D’Alessio DA, Seeley RJ. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab 2005;288:E447–E453.CrossRefPubMedGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2009

Authors and Affiliations

  • Feng Li
    • 1
  • Guangyong Zhang
    • 1
  • Jianwei Liang
    • 1
  • Xiangjiu Ding
    • 1
  • Zhiqiang Cheng
    • 1
  • Sanyuan Hu
    • 1
  1. 1.Department of General SurgeryQilu Hospital of Shandong UniversityJinanPeople’s Republic of China

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