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

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.

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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

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Correspondence to Young Min Cho.

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All animal experiments were approved by the Institutional Animal Care and Use (approval no. 15-0113-C1A1).

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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

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Keywords

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