Ileal transposition (IT) is a surgical procedure to investigate the role of the distal small intestine in metabolic improvements induced by bariatric/metabolic surgery, which has been applied to some human cases. We performed IT in diet-induced obese rats to investigate the effect of IT on glucose metabolism and β cell senescence.
Sprague-Dawley rats were fed high-fat diet (60% of total calories from fat) for 12 weeks and randomized into either IT or sham surgery. In the IT group, the distal ileal segment located between 5 and 15 cm proximal to the ileocecal valve was transposed 10 cm distal to the Treitz ligament isoperistaltically. In the sham surgery group, 3 corresponding transections of the intestine were made at the same locations as in IT and reattached in situ. β cell senescence was examined by the expression of two markers in vivo, p53BP1 and p16.
IT did not have a significant effect on body weight and insulin sensitivity, but postprandial insulin secretion was significantly increased. Glucagon-like peptide-1 (GLP-1) and peptide YY secretion were also increased after IT. The histology of the transposed ileum showed distinct hypertrophy with increased GLP-1 positive enteroendocrine cells. Pancreatic β cell area was significantly increased in the IT group. The percentage of p16 or p53BP1 positive senescent β cells was significantly lower in the IT group versus the sham group.
IT improved glucose tolerance in diet-induced obese rats mainly through augmented insulin secretion. This improvement was associated with attenuated β cell senescence.
This is a preview of subscription content, log in to check access.
Buy single article
Instant unlimited access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Roux-en-Y gastric bypass
type 2 diabetes mellitus
senescence-associated secretary phenotype
homeostatic model assessment for insulin resistance
area under the curve
oral glucose tolerance test
glucose-dependent insulinotropic polypeptide
tumor necrosis factor-α
monocyte chemoattractant protein-1
Bray GA, Fruhbeck G, Ryan DH, et al. Management of obesity. Lancet. 2016;387(10031):1947–56.
Rubino F, Schauer PR, Kaplan LM, et al. Metabolic surgery to treat type 2 diabetes: clinical outcomes and mechanisms of action. Annu Rev Med. 2010;61:393–411.
Cho YM. A gut feeling to cure diabetes: potential mechanisms of diabetes remission after bariatric surgery. Diabetes Metab J. 2014;38(6):406–15.
Jorsal T, Rhee NA, Pedersen J, et al. Enteroendocrine K and L cells in healthy and type 2 diabetic individuals. Diabetologia. 2018;61(2):284–94.
Oh TJ, Ahn CH, Cho YM. Contribution of the distal small intestine to metabolic improvement after bariatric/metabolic surgery: lessons from ileal transposition surgery. J Diabetes Investig. 2016;7(Suppl 1):94–101.
Koopmans HS, Sclafani A. Control of body weight by lower gut signals. Int J Obes. 1981;5(5):491–5.
De Paula AL, Stival AR, Macedo A, et al. Prospective randomized controlled trial comparing 2 versions of laparoscopic ileal interposition associated with sleeve gastrectomy for patients with type 2 diabetes with BMI 21-34 kg/m(2). Surg Obes Relat Dis. 2010;6(3):296–304.
Culnan DM, Albaugh V, Sun M, et al. Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G751–60.
Ikezawa F, Shibata C, Kikuchi D, et al. Effects of ileal interposition on glucose metabolism in obese rats with diabetes. Surgery. 2012;151(6):822–30.
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.
Cummings BP, Strader AD, Stanhope KL, et al. Ileal interposition surgery improves glucose and lipid metabolism and delays diabetes onset in the UCD-T2DM rat. Gastroenterology. 2010;138(7):2437–46, 46.e1.
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.
Palmer AK, Tchkonia T, LeBrasseur NK, et al. Cellular senescence in type 2 diabetes: a therapeutic opportunity. Diabetes. 2015;64(7):2289–98.
Tavana O, Puebla-Osorio N, Sang M, et al. Absence of p53-dependent apoptosis combined with nonhomologous end-joining deficiency leads to a severe diabetic phenotype in mice. Diabetes. 2010;59(1):135–42.
Coppe JP, Patil CK, Rodier F, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008;6(12):2853–68.
Sone H, Kagawa Y. Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia. 2005;48(1):58–67.
Uchida T, Nakamura T, Hashimoto N, et al. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat Med. 2005;11(2):175–82.
Oh TJ, Lee HJ, Cho YM. Ileal transposition decreases plasma lipopolysaccharide levels in association with increased L cell secretion in non-obese non-diabetic rats. Obes Surg. 2016;26(6):1287–95.
Ahn CH, Chae S, Oh TJ, Hwang D, Cho YM. Dynamic adaptive changes of the ileum transposed to the proximal small intestine in rats. Obes Surg. 2019 Apr 29.
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.
Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153(6):1194–217.
Krishnamurthy J, Torrice C, Ramsey MR, et al. Ink4a/Arf expression is a biomarker of aging. J Clin Invest. 2004;114(9):1299–307.
Aguayo-Mazzucato C, van Haaren M, Mruk M, et al. Beta cell aging markers have heterogeneous distribution and are induced by insulin resistance. Cell Metab. 2017;25(4):898–910.e5.
Aguayo-Mazzucato C, Andle J, Lee Jr TB, et al. Acceleration of beta cell aging determines diabetes and senolysis improves disease outcomes. Cell Metab. 2019;30(1):129–42.e4.
Cavin JB, Couvelard A, Lebtahi R, et al. Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology. 2016;150(2):454–64.e9.
Scheithauer TP, Dallinga-Thie GM, de Vos WM, et al. Causality of small and large intestinal microbiota in weight regulation and insulin resistance. Mol Metab. 2016;5(9):759–70.
Liou AP, Paziuk M, Luevano Jr JM, et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):178ra41.
Seeley RJ, Chambers AP, Sandoval DA. The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes. Cell Metab. 2015;21(3):369–78.
Shin CS, Lee HK, Koh CS, et al. Risk factors for the development of NIDDM in Yonchon County. Korea Diabetes Care. 1997;20(12):1842–6.
Control CfD, Prevention. National diabetes statistics report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services. 2017.
Rankin MM, Kushner JA. Adaptive beta-cell proliferation is severely restricted with advanced age. Diabetes. 2009;58(6):1365–72.
Kushner JA. The role of aging upon beta cell turnover. J Clin Invest. 2013;123(3):990–5.
Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8(9):729–40.
Wen J, Xue T, Huang Y, et al. Is beta-cell aging involved in the pathogenesis of diabetes? J Diabetes. 2017;9(7):707–16.
Vilsboll T. The effects of glucagon-like peptide-1 on the beta cell. Diabetes Obes Metab. 2009;11(Suppl 3):11–8.
Oeseburg H, de Boer RA, Buikema H, et al. Glucagon-like peptide 1 prevents reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A. Arterioscler Thromb Vasc Biol. 2010;30(7):1407–14.
Liao P, Yang D, Liu D, et al. GLP-1 and ghrelin attenuate high glucose/high lipid-induced apoptosis and senescence of human microvascular endothelial cells. Cell Physiol Biochem. 2017;44(5):1842–55.
Pluquet O, Pourtier A, Abbadie C. The unfolded protein response and cellular senescence. A review in the theme: cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. Am J Phys Cell Phys. 2015;308(6):C415–25.
Huang H, Lei H, Yang F, et al. Activation of the bile acid receptor GPBAR1 (TGR5) ameliorates interleukin-1beta induced chondrocytes senescence. Biomed Pharmacother. 2018;106:1713–9.
Rao SR. Inflammatory markers and bariatric surgery: a meta-analysis. Inflamm Res. 2012;61(8):789–807.
Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes. 2005;54(8):2277–86.
Zhang H, Wang Y, Zhang J, et al. Bariatric surgery reduces visceral adipose inflammation and improves endothelial function in type 2 diabetic mice. Arterioscler Thromb Vasc Biol. 2011;31(9):2063–9.
Belkaid Y, Harrison OJ. Homeostatic immunity and the microbiota. Immunity. 2017;46(4):562–76.
Postler TS, Ghosh S. Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metab. 2017;26(1):110–30.
Conflict of Interest
The authors declare that they have no conflicts of interest.
Statement of Animal Rights/Ethical Approval (Blinded)
All animal experiments were approved by the Institutional Animal Care and Use (approval no. 15-0113-C1A1).
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic Supplementary Material
About this article
Cite this article
Ahn, C.H., Choi, E.H., Oh, T.J. et al. Ileal Transposition Increases Pancreatic β Cell Mass and Decreases β Cell Senescence in Diet-Induced Obese Rats. OBES SURG (2020) doi:10.1007/s11695-020-04406-6
- Ileal transposition
- β cell senescence
- β cell mass
- Glucagon-like peptide-1