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Ileal Transposition Increases Pancreatic β Cell Mass and Decreases β Cell Senescence in Diet-Induced Obese Rats

  • Chang Ho Ahn
  • Eun Hye Choi
  • Tae Jung Oh
  • Young Min ChoEmail author
Original Contributions

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

IT improved glucose tolerance in diet-induced obese rats mainly through augmented insulin secretion. This improvement was associated with attenuated β cell senescence.

Keywords

Ileal transposition β cell senescence β cell mass Glucagon-like peptide-1 

Abbreviations

IT

ileal transposition

GLP-1

glucagon-like peptide-1

RYGB

Roux-en-Y gastric bypass

T2DM

type 2 diabetes mellitus

PYY

peptide YY

SASP

senescence-associated secretary phenotype

HOMA-IR

homeostatic model assessment for insulin resistance

AUC

area under the curve

OGTT

oral glucose tolerance test

GIP

glucose-dependent insulinotropic polypeptide

TNF-α

tumor necrosis factor-α

MCP-1

monocyte chemoattractant protein-1

HIF-1a

hypoxia-inducible factor-1a

IL-1b

interleukin-1b

Notes

Funding Information

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1277).

Compliance with Ethical Standards

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).

Supplementary material

11695_2020_4406_MOESM1_ESM.docx (20 kb)
ESM1 (DOCX 20 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Internal MedicineSeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Department of Translational Medicine, College of MedicineSeoul National UniversitySeoulRepublic of Korea
  3. 3.Department of Internal MedicineSeoul National University Bundang HospitalSeongnamRepublic of Korea
  4. 4.Department of Internal MedicineSeoul National University HospitalSeoulRepublic of Korea

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