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Expedited Biliopancreatic Juice Flow to the Distal Gut Benefits the Diabetes Control After Duodenal-Jejunal Bypass

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Abstract

Background

Serum bile acids (BAs) are elevated after metabolic surgeries including Roux-en-Y gastric bypass (RYGB), ileal transposition (IT), and duodenal-jejunal bypass (DJB). Recently, BAs have emerged as a kind of signaling molecules, which can not only promote glucagon-like peptide-1 (GLP-1) secretion but can also regulate multiple enzymes involved in glucose metabolism. The aim of this study was to investigate whether expedited biliopancreatic juice flow to the distal gut contributes to the increased serum GLP-1 and BAs and benefits the diabetes control after DJB.

Methods

DJB, long alimentary limb DJB (LDJB), duodenal-jejunal anastomosis (DJA), and sham operation were performed in diabetic rats induced by high-fat diet (HFD) and low dose of streptozotocin (STZ). Body weight, food intake, oral glucose tolerance, insulin tolerance, glucose-stimulated insulin and GLP-1 secretion, fasting serum total bile acids (TBAs), and lipid profiles were measured at indicated time points.

Results

Compared with sham operation, DJA, DJB, and LDJB all achieved rapid and dramatic improvements in glucose tolerance and insulin sensitivity independently of food restriction and weight loss. DJB and LDJB-operated rats exhibited even better glucose tolerance, higher fasting serum TBAs, and higher glucose-stimulated GLP-1 secretion than the DJA group postoperatively. No difference was detected in insulin sensitivity and glucose-stimulated insulin secretion between DJA, DJB, and LDJB groups.

Conclusions

Expedited biliopancreatic juice flow to the distal gut was associated with augmented GLP-1 secretion and increased fasting serum TBA concentration, which may partly explain the metabolic benefits of DJB.

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References

  1. 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):1–11.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Jiao J, Bae EJ, Bandyopadhyay G, et al. Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats. Diabetes. 2013;62(4):1074–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Jurowich CF, Rikkala PR, Thalheimer A, et al. Duodenal-jejunal bypass improves glycemia and decreases SGLT1-mediated glucose absorption in rats with streptozotocin-induced type 2 diabetes. Ann Surg. 2013;258(1):89–97.

    Article  PubMed  Google Scholar 

  4. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244(5):741–9.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Kindel TL, Yoder SM, Seeley RJ, et al. Duodenal-jejunal exclusion improves glucose tolerance in the diabetic, Goto-Kakizaki rat by a GLP-1 receptor-mediated mechanism. J Gastrointest Surg. 2009;13(10):1762–72.

    Article  PubMed  Google Scholar 

  6. Patti ME, Houten SM, Bianco AC, et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring). 2009;17(9):1671–7.

    Article  CAS  Google Scholar 

  7. Cummings BP, Bettaieb A, Graham JL, et al. Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats. Dis Model Mech. 2013;6(2):443–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Han H, Hu C, Wang L, et al. Duodenal-jejunal bypass surgery suppresses hepatic de novo lipogenesis and alleviates liver fat accumulation in a diabetic rat model. Obes Surg. 2014;24(12):2152–60.

    Article  PubMed  Google Scholar 

  9. Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J. 2006;25(7):1419–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Ma K, Saha PK, Chan L, et al. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116(4):1102–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Watanabe M, Houten SM, Wang L, et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest. 2004;113(10):1408–18.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238(4):467–84. discussion 84–5.

    PubMed Central  PubMed  Google Scholar 

  14. Wang TT, Hu SY, Gao HD, et al. Ileal transposition controls diabetes as well as modified duodenal jejunal bypass with better lipid lowering in a nonobese rat model of type II diabetes by increasing GLP-1. Ann Surg. 2008;247(6):968–75.

    Article  PubMed  Google Scholar 

  15. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3):248–56. 3.

    Article  PubMed  Google Scholar 

  16. Eissele R, Goke R, Willemer S, et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Investig. 1992;22(4):283–91.

    Article  CAS  Google Scholar 

  17. Srinivasan K, Viswanad B, Asrat L, et al. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005;52(4):313–20.

    Article  CAS  PubMed  Google Scholar 

  18. Liu SZ, Sun D, Zhang GY, et al. A high-fat diet reverses improvement in glucose tolerance induced by duodenal-jejunal bypass in type 2 diabetic rats. Chin Med J. 2012;125(5):912–9.

    CAS  PubMed  Google Scholar 

  19. Liu S, Zhang G, Wang L, et al. The entire small intestine mediates the changes in glucose homeostasis after intestinal surgery in Goto-Kakizaki rats. Ann Surg. 2012;256(6):1049–58.

    Article  PubMed  Google Scholar 

  20. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.

    Article  CAS  PubMed  Google Scholar 

  21. 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. Ann Surg. 1995;222(3):339–50. discussion 50–2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Thaler JP, Cummings DE. Minireview: hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology. 2009;150(6):2518–25.

    Article  CAS  PubMed  Google Scholar 

  23. Knop FK. Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling? Diabetologia. 2009;52(11):2270–6.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang SY, Sun XJ, Zheng JB, et al. Preserve common limb in duodenal-jejunal bypass surgery benefits rats with type 2-like diabetes. Obes Surg. 2014;24(3):405–11.

    Article  PubMed  Google Scholar 

  25. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–57.

    Article  CAS  PubMed  Google Scholar 

  26. Drucker DJ. The role of gut hormones in glucose homeostasis. J Clin Invest. 2007;117(1):24–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Brubaker PL. The glucagon-like peptides: pleiotropic regulators of nutrient homeostasis. Ann N Y Acad Sci. 2006;1070:10–26.

    Article  CAS  PubMed  Google Scholar 

  28. Parker HE, Wallis K, le Roux CW, et al. Molecular mechanisms underlying bile acid-stimulated glucagon-like peptide-1 secretion. Br J Pharmacol. 2012;165(2):414–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Wu T, Bound MJ, Standfield SD, et al. Effects of taurocholic acid on glycemic, glucagon-like peptide-1, and insulin responses to small intestinal glucose infusion in healthy humans. J Clin Endocrinol Metab. 2013;98(4):E718–22.

    Article  CAS  PubMed  Google Scholar 

  30. Kohli R, Setchell KD, Kirby M, et al. A surgical model in male obese rats uncovers protective effects of bile acids post-bariatric surgery. Endocrinology. 2013;154(7):2341–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Pournaras DJ, Glicksman C, Vincent RP, et al. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology. 2012;153(8):3613–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Salinari S, le Roux CW, Bertuzzi A, et al. Duodenal-jejunal bypass and jejunectomy improve insulin sensitivity in Goto-Kakizaki diabetic rats without changes in incretins or insulin secretion. Diabetes. 2014;63(3):1069–78.

    Article  PubMed  Google Scholar 

  33. Speck M, Cho YM, Asadi A, et al. Duodenal-jejunal bypass protects GK rats from {beta}-cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1. Am J Physiol Endocrinol Metab. 2011;300(5):E923–32.

    Article  CAS  PubMed  Google Scholar 

  34. Steinert RE, Peterli R, Keller S, et al. Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Obesity (Silver Spring). 2013;21(12):E660–8.

    Article  CAS  Google Scholar 

  35. Kohli R, Kirby M, Setchell KD, et al. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G652–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484–9.

    Article  CAS  PubMed  Google Scholar 

  37. Kuipers F, Groen AK. FXR: the key to benefits in bariatric surgery? Nat Med. 2014;20(4):337–8.

    Article  CAS  PubMed  Google Scholar 

  38. Angelin B, Bjorkhem I, Einarsson K, et al. Hepatic uptake of bile acids in man. Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum. J Clin Investig. 1982;70(4):724–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Mencarelli A, Renga B, D’Amore C, et al. Dissociation of intestinal and hepatic activities of FXR and LXRα supports metabolic effects of terminal ileum interposition in rodents. Diabetes. 2013;62(10):3384–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81270888/H0713, no. 81370496/H0308, no. 81300286/H0308), Natural Science Foundation of Shandong Province grants (no. ZR2009CM051), and the Taishan Scholar Foundation.

Conflict of Interest

We declare that all authors have no conflict of interest.

Statement of Informed Consent

Does not apply.

Statement of Human and Animal Rights

All applicable institutional and national guidelines for the care and use of animals were followed.

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    Authors and Affiliations

    1. Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong, People’s Republic of China

      Haifeng Han, Lei Wang, Jianjun Jiang, Chunxiao Hu, Guangyong Zhang, Shaozhuang Liu, Xiang Zhang, Teng Liu & Sanyuan Hu

    2. School of Medicine, Shandong University, 44 West Wenhua Road, Jinan, 250012, Shandong, People’s Republic of China

      Hao Du

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    1. Haifeng Han
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    Correspondence to Sanyuan Hu.

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    Haifeng Han and Lei Wang contributed equally to this work.

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    Han, H., Wang, L., Du, H. et al. Expedited Biliopancreatic Juice Flow to the Distal Gut Benefits the Diabetes Control After Duodenal-Jejunal Bypass. OBES SURG 25, 1802–1809 (2015). https://doi.org/10.1007/s11695-015-1633-7

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