Skip to main content
SpringerLink
Log in

Ileal Effect on Blood Glucose, HbA1c, and GLP-1 in Goto-Kakizaki Rats

  • Original Contributions
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Background

There have been enumerable studies on the effects of glucagon-like peptide-1 (GLP-1) on satiety and pancreatic islet function, stimulating the advocacy of surgical transposition of the ileum (rich in GLP-1-generating L-cells) higher in the gastrointestinal tract for earlier stimulation. In the Goto-Kakizaki rat with naturally occurring type 2 diabetes, we studied the influence of ileal exclusion (IE) and ileal resection (IR) on blood glucose, hemoglobin A1c (HbA1c), and GLP-1.

Methods

In six control (Ctrl), 10 IE, and 10 IR rats, over 12 weeks of follow-up, we determined blood glucose, HbA1c, and GLP-1.

Results

Two animals in the IE and IR groups did not survive to week 13. Both operated groups weighed more than the Ctrl group at baseline and at 13 weeks; thus, IE and IR did not retard weight gain (p < 0.05). All three groups were equally hyperglycemic at week 13: 255 ± 10.2 Ctrl, 262 ± 11.0 IE, 292 ± 17.8 IR (mg/dl ± SEM). The three groups had statistically identical markedly elevated HbA1c percentages at week 13: 14.7 ± 28 Ctrl, 11.7 ± 3.4 IE, 13.8 ± 3.5 IR (% ± SEM). The end-study GLP-1 values (pM ± SEM) were 5 ± 0.9 Ctrl, 33 ± 8.9 IE, and 25 ± 6.7 IR. P values for intergroup differences were IE vs. Ctrl 0.02, IR vs. Ctrl 0.02, and IE vs. IR 0.59.

Conclusions

Neither IE nor IR resulted in a decrease in the mean GLP-1 level. On the contrary, the exclusion or resection of the L-cell rich ileum raised GLP-1 levels 5- to 6-fold. This increase in the GLP-1 was not associated with the mitigation of hyperglycemia or elevated HbA1c levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Naslund E, Bogefors J, Skogar S, et al. GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. Am J Physiol Regul Integr Comp Physiol. 1999;277:R910–6.

    CAS  Google Scholar 

  2. Adrian TE, Ferre G-L, Bacarese-Hamilton AJ, et al. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology. 1985;89:1070–7.

    PubMed  CAS  Google Scholar 

  3. Greeley Jr GH, Hashimoto T, Izukura M, et al. A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog. Endocrinology. 1989;125:1761–5.

    Article  PubMed  CAS  Google Scholar 

  4. Zhang T, Brubaker PL, Thompson JC, et al. Characterization of peptide-YY release in response to intracolonic infusion of amino acids. Endocrinology. 1993;132:553–7.

    PubMed  CAS  Google Scholar 

  5. Aponte GW, Fink AS, Meyer JH, et al. Regional distribution and release of peptide YY with fatty acids of different chain length. Am J Physiol. 1985;249:G745–50.

    PubMed  CAS  Google Scholar 

  6. Adrian TE, Ballantyne GH, Longo WE, et al. Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. Gut. 1993;34:1219–24.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Onaga T, Zabielski R, Kato S. Multiple regulation of peptide YY secretion in the digestive tract. Peptides. 2002;23:279–90.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang T, Uchida T, Gomez G, et al. Neural regulation of peptide YY secretion. Regul Pept. 1993;48:321–8.

    Article  PubMed  CAS  Google Scholar 

  9. Rudnicki M, Rigel DF, McFadden DW. Vagal cooling blocks circulating neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) release. J Surg Res. 1991;51:40–5.

    Article  PubMed  CAS  Google Scholar 

  10. Ballantyne GH, Goldenring JR, Savoca PE, et al. Cyclic AMP-mediated release of peptide YY (PYY) from the isolated perfused rabbit distal colon. Regul Pept. 1993;47:117–26.

    Article  PubMed  CAS  Google Scholar 

  11. Greeley Jr GH, Jeng YJ, Gomez G, et al. Evidence for regulation of peptide-YY release by the proximal gut. Endocrinology. 1989;124:1438–43.

    Article  PubMed  CAS  Google Scholar 

  12. Hernandez EJ, Whitcomb DC, Vigna SR, et al. Saturable binding of circulating peptide YY in the dorsal vagal complex of rats. Am J Physiol Gastrointest Liver Physiol. 1994;226:G511–6.

    Google Scholar 

  13. Druce MR, Small CJ, Bloom SR. Minireview: Gut peptides regulating satiety. Endocrinology. 2004;145:2660–5.

    Article  PubMed  CAS  Google Scholar 

  14. Korner J, Leibel RL. To eat or not to eat—how the gut talks to the brain. N Engl J Med. 2003;349:926–8.

    Article  PubMed  CAS  Google Scholar 

  15. Savage AP, Adrian TE, Carolan G, et al. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers. Gut. 1987;28:166–70.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Spiller RC, Trotman IF, Adrian TE, et al. Further characterization of the ‘ileal brake’ reflex in man—effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY. Gut. 1988;29:1042–51.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Spiller RC, Trotman IF, Higgins BE, et al. The ileal brake—inhibition of jejunal motility after ileal fat perfusion in man. Gut. 1984;25:365–74.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Tolhurst G, Reimann F, Gribble FM. Nutritional regulation of glucagon-like peptide-1 secretion. J Physiol. 2009;587:27–32.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Lim GE, Brubaker PL. Glucagon-like peptide 1 secretion by the L-cell. The view from within. Diabetes. 2006;55:S70–7.

    Article  CAS  Google Scholar 

  20. Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3:153–65.

    Article  PubMed  CAS  Google Scholar 

  21. Mason EE. Ileal transposition and enteroglucagon/GLP-1 in obesity (and diabetic?) surgery. Obes Surg. 1999;9:223–8.

    Article  PubMed  CAS  Google Scholar 

  22. Gagner M. Surgical treatment of nonseverely obese patients with type 2 diabetes mellitus: sleeve gastrectomy with ileal transposition (SGIT) is the same as the neuroendocrine brake (NEB) procedure or ileal interposition associated with sleeve gastrectomy (II-SG), but ileal interposition with diverted sleeve gastrectomy (II-DSG) is the same as duodenal switch. Surg Endosc. 2001;25:655–6.

    Article  Google Scholar 

  23. DePaula AL, Stival AR, DePaula CC, et al. Surgical treatment of type 2 diabetes in patients with BMI below 35: mid-term outcomes of the laparoscopic ileal interposition associated with a sleeve gastrectomy in 202 consecutive cases. J Gastrointest Surg. 2012;16:967–76.

    Article  PubMed  Google Scholar 

  24. 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;247:968–75.

    Article  PubMed  Google Scholar 

  25. Tsuchiga T, Kalogeris TJ, Tso P. Ileal transposition into the upper jejunum affects lipid and bile salt absorption in rats. Am J Physiol. 1996;271:G681–91.

    Google Scholar 

  26. Strader AD, Vahl TP, Jandacek RJ, et al. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab. 2005;288:E447–53.

    Article  PubMed  CAS  Google Scholar 

  27. Buchwald H, Dorman RB, Rasmus NF, Michalek VN, Landvik NM, Ikramuddin S. Effects on GLP-1, PYY, and leptin by direct stimulation of terminal ileum and cecum in humans: implications for ileal transposition. Surg Obes Relat Dis 2014. doi:10.1016/j.soard.2014.01.032.

  28. Nilsson O, Bilchik AJ, Goldenring JR, et al. Distribution and immunocytochemical colocalization of peptide YY and enteroglucagon in endocrine cells of the rabbit colon. Endocrinology. 1991;129:139–48.

    Article  PubMed  CAS  Google Scholar 

  29. Buchwald H. Lowering of cholesterol absorption and blood levels by ileal exclusion: experimental basis and preliminary clinical report. Circulation. 1964;29:713–20.

    Article  PubMed  CAS  Google Scholar 

  30. Moore RB, Frantz Jr ID, Buchwald H. Changes in cholesterol pool size, turnover rate, and fecal bile acid and sterol excretion after partial ileal bypass in hypercholesterolemic patients. Surgery. 1969;65:98–108.

    PubMed  CAS  Google Scholar 

  31. Scott Jr HW, Stephenson Jr SE, Younger R, et al. Prevention of experimental atherosclerosis by ileal bypass: 20 % cholesterol diet and I-131 induced hypothyroidism in dogs. Ann Surg. 1966;163:795–807.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gomes MM, Kottke BA, Bernatz P, et al. Effect of ileal bypass on aortic atherosclerosis of white Carneau pigeons. Surgery. 1971;70:353–8.

    PubMed  CAS  Google Scholar 

  33. Shepard GH, Wimberly JE, Younger RK, et al. Effects of bypass of the distal third of the small intestine on experimental hypercholesterolemia and atherosclerosis in rhesus monkeys. Surg Forum. 1968;19:302.

    PubMed  CAS  Google Scholar 

  34. Scott Jr HW, Stephenson Jr SE, Hayes CW, et al. Effects of bypass of the distal fourth of small intestine on experimental hypercholesterolemia and atherosclerosis in rhesus monkeys. Surg Gynecol Obstet. 1967;125:3–12.

    PubMed  Google Scholar 

  35. Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med. 1990;323:946–55.

    Article  PubMed  CAS  Google Scholar 

  36. Buchwald H, Matts JP, Fitch LL, et al. Changes in sequential coronary arteriograms and subsequent coronary events. JAMA. 1992;268:1429–33.

    Article  PubMed  CAS  Google Scholar 

  37. Buchwald H, Campos CT, Varco RL, et al. Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Arch Intern Med. 1998;158:1253–61.

    Article  PubMed  CAS  Google Scholar 

  38. Buchwald H, Rudser KD, Williams SE, et al. Overall mortality, incremental life expectancy, and cause of death at 25-years in the Program on the Surgical Control of the Hyperlipidemias (POSCH). Ann Surg. 2010;251(6):1034–40.

    Article  PubMed  Google Scholar 

Download references

Acknwledgments

Funded by a grant from the Robert and Katherine Goodale Chair in Minimally Invasive Surgery, Department of Surgery, University of Minnesota.

Conflict of Interest

Henry Buchwald, Hector J. Menchaca, Van N. Michalek, and Nestor T. Bertin Suguitani have nothing to disclose.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 290, Minneapolis, MN, 55455, USA

    Henry Buchwald, Hector J. Menchaca, Van N. Michalek & Nestor T. Bertin

Authors
  1. Henry Buchwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hector J. Menchaca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Van N. Michalek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nestor T. Bertin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henry Buchwald.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Buchwald, H., Menchaca, H.J., Michalek, V.N. et al. Ileal Effect on Blood Glucose, HbA1c, and GLP-1 in Goto-Kakizaki Rats. OBES SURG 24, 1954–1960 (2014). https://doi.org/10.1007/s11695-014-1307-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-014-1307-x

Keywords

Search

Navigation