Advertisement

Distal gastric mucosa ablation induces significant weight loss and improved glycemic control in type 2 diabetes Sprague–Dawley rat model

  • Ponnie Robertlee Dolo
  • Ke Huang
  • Jason Widjaja
  • Chao Li
  • Xiaocheng ZhuEmail author
  • Libin Yao
  • Jian Hong
Article

Abstract

Background

Excluding the foregut (distal stomach and duodenum) from food transit in RYGB normalizes glucose tolerance. Excluding/removing the duodenal mucosa partly improves glycemic control. So far, the effect of excluding/removing the gastric mucosa remains unknown.

Objective

To observe the effect of removing the distal gastric mucosa on glucose tolerance.

Method

Thirty fatty Sprague–Dawley rats received low-dose streptozotocin (STZ) to induce type 2 diabetes (T2D), then randomly assigned to Roux-en-Y gastric bypass (RYGB, n = 8), distal gastric mucosa removal (DGMR, n = 8), duodenal–jejunal bypass (DJB, n = 8), and Sham (n = 6) groups. In the DGMR group, the distal third of the gastric mucosa was removed by thermal ablation using an electrocautery. Rats were followed for 8 weeks postoperatively. Preoperative oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and mixed-meal tolerance test (MMTT) were repeated 3 and 6 weeks postoperatively. Changes in body weight, food intake, and fasting blood glucose were also recorded.

Results

Gastrin AUC decreased significantly (p < 0.05) in the DGMR group after surgery. A significantly increased GLP-1 AUC was found in the RYGB, DGMR, and DJB groups at week 3 and only the RYGB group at week 6 postoperatively. The improved glucose tolerance in the RYGB group was significantly greater than the improved glucose tolerance in the DGMR and DJB groups. The improved glucose tolerance 3 and 6 weeks after surgery in the DGMR group was significantly greater than the improved glucose tolerance in the DJB group. Body weight decreased significantly in the RYGB, DGMR, and DJB groups postoperatively.

Conclusion

Removing the distal gastric mucosa induced significant weight loss and improved glycemic control in T2D SD rat model. Therefore, the gastric mucosa exclusion in RYGB may be key to the weight loss and diabetes remission, which perhaps warrants a new theory.

Keywords

Gastric bypass Type 2 diabetes Foregut Gastric mucosa GLP-1 Gastrin 

Notes

Author contribution

PRD and XZ designed the experiment. PRD performed the experiment and drafted the manuscript. CL and XZ supervised the experiment and offered technical support. LY, JW, and JH revised the manuscript, and KH provided material and logistical support.

Funding

Funding was provided by Natural Science Foundation of Jiangsu Province (2015102015).

Compliance with ethical standards

Disclosures

Dr. Ponnie Robertlee Dolo, Dr. Ke Huang, Dr. Jason Widjaja, Dr. Chao Li, Dr. Xiaocheng Zhu, Dr. Libin Yao, and Dr. Jian Hong have no conflict of interest or financial ties to disclose.

Informed consent

Not applicable (there were no human participants).

Research involved in human and animal rights

All applicable institutional and national guidelines of the People’s Republic of China for the care and use of animals were followed.

References

  1. 1.
    Peterli R, Wolnerhanssen BK, Vetter D, Nett P, Gass M, Borbely Y, Peters T, Schiesser M, Schultes B, Beglinger C et al (2017) Laparoscopic sleeve gastrectomy versus Roux-Y-gastric bypass for morbid obesity-3-year outcomes of the prospective randomized Swiss Multicenter Bypass Or Sleeve Study (SM-BOSS). Ann Surg 265(3):466–473CrossRefGoogle Scholar
  2. 2.
    Perrone F, Bianciardi E, Ippoliti S, Nardella J, Fabi F, Gentileschi P (2017) Long-term effects of laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass for the treatment of morbid obesity: a monocentric prospective study with minimum follow-up of 5 years. Updates Surg 69(1):101–107CrossRefGoogle Scholar
  3. 3.
    Allen RE, Hughes TD, Ng JL, Ortiz RD, Ghantous MA, Bouhali O, Froguel P, Arredouani A (2013) Mechanisms behind the immediate effects of Roux-en-Y gastric bypass surgery on type 2 diabetes. Theor Biol Med Model 10:45CrossRefGoogle Scholar
  4. 4.
    Rubino F, Gagner M, Gentileschi P, Kini S, Fukuyama S, Feng J, Diamond E (2004) The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg 240(2):236–242CrossRefGoogle Scholar
  5. 5.
    Li P, Zhu L, Wang G, Yang X, Yi B, Zhu S (2016) The role of foregut exclusion in the deterioration of glucose and lipid metabolism induced by a high-fat diet. Diabetes Res Clin Pract 114:83–92CrossRefGoogle Scholar
  6. 6.
    Rubino F, Marescaux J (2004) Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg 239(1):1–11CrossRefGoogle Scholar
  7. 7.
    Dolo PR, Shao Y, Li C, Zhu X, Yao L, Wang H (2019) The effect of gastric bypass with a distal gastric pouch on glucose tolerance and diabetes remission in type 2 diabetes Sprague–Dawley rat model. Obes Surg 29(6):1889–1900CrossRefGoogle Scholar
  8. 8.
    Oberbach A, Schlichting N, Heinrich M, Kullnick Y, Retschlag U, Lehmann S, Khashab MA, Kalloo AN, Kumbhari V (2018) Gastric mucosal devitalization reduces adiposity and improves lipid and glucose metabolism in obese rats. Gastrointest Endosc 87(1):288e286–299e286CrossRefGoogle Scholar
  9. 9.
    Zhang M, Lv XY, Li J, Xu ZG, Chen L (2008) The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp Diabetes Res 2008:704045CrossRefGoogle Scholar
  10. 10.
    Dolo PR, Li C, Zhu X, Yao L, Meng S, Hong J (2018) The effect of distal-ileal exclusion after Roux-en-Y gastric bypass on glucose tolerance and GLP-1 response in type-2 diabetes Sprague–Dawley rat model. Surg Obes Relat Dis 14(10):1552–1560CrossRefGoogle Scholar
  11. 11.
    Davis DB, Khoraki J, Ziemelis M, Sirinvaravong S, Han JY, Campos GM (2018) Roux en Y gastric bypass hypoglycemia resolves with gastric feeding or reversal: confirming a non-pancreatic etiology. Mol Metab 9:15–27CrossRefGoogle Scholar
  12. 12.
    Jirapinyo P, Thompson AC, Kroner PT, Chan WW, Thompson CC (2018) Metabolic effect of foregut exclusion demonstrated by the impact of gastrogastric fistula on recurrence of diabetes. J Am Coll Surg 226(3):259e251–266e251CrossRefGoogle Scholar
  13. 13.
    Tellez N, Joanny G, Escoriza J, Vilaseca M, Montanya E (2011) Gastrin treatment stimulates beta-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats. Endocrinology 152(7):2580–2588CrossRefGoogle Scholar
  14. 14.
    Grong E, Graeslie H, Munkvold B, Arbo IB, Kulseng BE, Waldum HL, Marvik R (2016) Gastrin secretion after bariatric surgery-response to a protein-rich mixed meal following Roux-En-Y gastric bypass and sleeve gastrectomy: a pilot study in normoglycemic women. Obes Surg 26(7):1448–1456CrossRefGoogle Scholar
  15. 15.
    Stenstrom B, Zhao CM, Tommeras K, Arum CJ, Chen D (2006) Is gastrin partially responsible for body weight reduction after gastric bypass? Eur Surg Res 38(2):94–101CrossRefGoogle Scholar
  16. 16.
    Persson P, Hakanson R, Axelson J, Sundler F (1989) Gastrin releases a blood calcium-lowering peptide from the acid-producing part of the rat stomach. Proc Natl Acad Sci USA 86(8):2834–2838CrossRefGoogle Scholar
  17. 17.
    Svane MS, Bojsen-Moller KN, Martinussen C, Dirksen C, Madsen JL, Reitelseder S, Holm L, Rehfeld JF, Kristiansen VB, van Hall G et al (2019) postprandial nutrient handling and gastrointestinal hormone secretion after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology 156(6):1627e1621–1641e1621CrossRefGoogle Scholar
  18. 18.
    Theodorakis MJ, Carlson O, Michopoulos S, Doyle ME, Juhaszova M, Petraki K, Egan JM (2006) Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab 290(3):E550–E559CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of General SurgeryThe Affiliated Hospital of Xuzhou Medical UniversityXuzhouPeople’s Republic of China
  2. 2.Institute of Digestive DiseasesXuzhou Medical UniversityXuzhouPeople’s Republic of China

Personalised recommendations