The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Gut Hypertrophy After Gastric Bypass Is Associated With Increased Glucagon-Like Peptide 2 and Intestinal Crypt Cell Proliferation
Abstract
OBJECTIVE: We aimed to determine changes in crypt cell proliferation and glucagon-like peptide-2 (GLP-2) in rodents and man after Roux-en-Y gastric bypass (RYGB). SUMMARY OF BACKGROUND DATA: Roux-en-Y gastric bypass results in sustained weight loss and reduced appetite with only mild gastrointestinal side effects. Glucagon-like peptide-2 released from intestinal l-cells after nutrient intake stimulates intestinal crypt cell proliferation and mitigates the effects of gut injury. METHODS: Wistar rats underwent either RYGB (n = 6) or sham procedure (n = 6) and plasma GLP-2, GLP-1, and gut hormone peptide YY (PYY) were measured after 23 days. Biopsies from the terminal ileum were stained using the antibody to Ki67, which detects cyclins and hence demonstrates cells in the S-phase of the cell cycle. The total number of cells, number of mitosis, and number of labeled cells per crypt were counted. Obese patients (n = 6) undergoing RYGB were evaluated following a 420 kcal meal preoperatively, and 1, 3, 6, 12, and 24 months later for responses in l-cell products such as GLP-2, GLP-1, total PYY, and PYY3-36. RESULTS: Rat GLP-2 levels after RYGB were elevated 91% above sham animals (P = 0.02). At necropsy, mitotic rate (P < 0.001) and cells positive for the antibody Ki67 (P < 0.001) were increased, indicating crypt cell proliferation. Human GLP-2 after RYGB reached a peak at 6 months of 168% (P < 0.01) above preoperative values. Area under the curve for GLP-1 (P < 0.0001), total PYY (P < 0.01), and PYY3-36 (P < 0.05) responses increased progressively over 24 months. CONCLUSIONS: RYGB leads to increased GLP-2 and mucosal crypt cell proliferation. Other gut hormones from l-cells remain elevated for at least 2 years in humans. These findings may account for the restoration of the absorptive surface area of the gut, which limits malabsorption and contributes to the long-term weight loss after RYGB.
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“A second factor may be the altered gut barrier function through either reduced bowel permeability from chronically increased secretion of GLP-2 or shifts in the intestinal microflora after surgery [130-132].”
From Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects (2020) · cites this paper as [130]
Citations
Cites
Bariatric Surgery: A Systematic Review and Meta-analysis
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Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery
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Gut hormone PYY3-36 physiologically inhibits food intake
Batterham, R. L., Cowley, M. A., Small, C. J., Herzog, H., Cohen, M. A., Dakin, C. L., Wren, A. M., Brynes, A. E., Low, M. J., Ghatei, M. A., et al. (2002) · Nature · doi:10.1038/nature00887 · Cited by 2,351
Self-citationGlucagon-like peptide-1 7–36: a physiological incretin in man
Kreymann, B., Ghatei, M. A., Williams, G., & Bloom, S. R. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91194-9 · Cited by 1,928
Self-citationInhibition of Food Intake in Obese Subjects by Peptide YY 3–36
Batterham, R. L., Cohen, M. A., Ellis, S. M., Le Roux, C. W., Withers, D. J., Frost, G. S., Ghatei, M. A., & Bloom, S. R. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030204 · Cited by 1,604
Self-citationRoux, C. W. L., Aylwin, S. J. B., Batterham, R. L., Borg, C. M., Coyle, F., Prasad, V., Shurey, S., Ghatei, M. A., Patel, A. G., & Bloom, S. R. (2006) · Annals of Surgery · doi:10.1097/01.sla.0000183349.16877.84 · Cited by 985
Self-citationGut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass
le Roux, C. W., Welbourn, R., Werling, M., Osborne, A., Kokkinos, A., Laurenius, A., Lönroth, H., Fändriks, L., Ghatei, M. A., Bloom, S. R., et al. (2007) · Annals of Surgery · doi:10.1097/sla.0b013e3180caa3e3 · Cited by 741 · cited 1×
“Suppression of the release of gut hormones such as PYY and GLP-1 with the somatostatin analogue octreotide after RYGB reverses the enhanced satiety and increases food intake acutely.(39) Although there may be additional satiety factors that contribute to reduced food intake after RYGB, taken together, these observatio…”
BackgroundSelf-citationCritical role for peptide YY in protein-mediated satiation and body-weight regulation
Batterham, R. L., Heffron, H., Kapoor, S., Chivers, J. E., Chandarana, K., Herzog, H., le Roux, C. W., Thomas, E. L., Bell, J. D., & Withers, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.08.001 · Cited by 653
Rubino, F., Gagner, M., Gentileschi, P., Kini, S. U., Fukuyama, S., Feng, J. J., & Diamond, E. (2004) · Annals of Surgery · doi:10.1097/01.sla.0000133117.12646.48 · Cited by 638
Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans
Holst, J. J., & Gromada, J. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00545.2003 · Cited by 611
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Cani, P. D., Osto, M., Geurts, L., & Everard, A. (2012) · Gut Microbes · doi:10.4161/gmic.19625 · Cited by 864
Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium
Gribble, F. M., & Reimann, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105439 · Cited by 683
Reprogramming of Intestinal Glucose Metabolism and Glycemic Control in Rats After Gastric Bypass
Saeidi, N., Meoli, L., Nestoridi, E., Gupta, N., Kvas, S., Kucharczyk, J. R., Bonab, A. A., Fischman, A. J., Yarmush, M. L., & Stylopoulos, N. (2013) · Science · doi:10.1126/science.1235103 · Cited by 343
The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones
Meek, C. L., Lewis, H. B., Reimann, F. M., Gribble, F. M., & Park, A. J. (2015) · Peptides · doi:10.1016/j.peptides.2015.08.013 · Cited by 276
The Role of GLP-1 in the Metabolic Success of Bariatric Surgery
Hutch, C. R., & Sandoval, D. A. (2017) · Endocrinology · doi:10.1210/en.2017-00564 · Cited by 245
Metadata
- Authors
- le Roux, C. W., Borg, C., Wallis, K., Vincent, R. P., Bueter, M., Goodlad, R., Ghatei, M. A., Patel, A., Bloom, S. R., & Aylwin, S. J. B.
- Affiliations
- King's College Hospital (GB)
- Imperial College London (GB)
- Institute of Cancer Research (GB)
- King's College London (GB)
- Corresponding author
- Wallis, Katharina
- Vincent, Royce P.
- Bueter, Marco
- Ghatei, Mohammed A.
- Bloom, Stephen R.
- ORCID
- Venue
- Annals of Surgery
- Published
- 2010-07
- Volume
- 252
- Issue
- 1
- Pages
- 50-56
- ISSN
- 0003-4932 (ISSN-L)
- OpenAlex
- W1972517166
- Cited by
- 176
- References
- 42
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 10 · 2021: 8 · 2020: 10 · 2019: 12 · 2018: 16 · 2017: 12 · 2016: 24 · 2015: 20 · 2014: 9 · 2013: 17 · 2012: 9
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Surgery (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0507-10337)
- Biotechnology and Biological Sciences Research Council (BB/E52708X/1)
- Topics
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Roux-en-Y gastric bypass, gastric bypass, glucagon-like peptide-2, glucagon-like peptide-1, peptide YY, PYY3-36, intestinal L cells, gastrointestinal hormones, Ki-67, terminal ileum, malabsorption, weight loss, bariatric surgery, rat model
- MeSH terms
- Adult, Animals, Female, Humans, Ileum, Intestinal Mucosa, Male, Middle Aged, Mitosis, Gastric Bypass, Rats, Wistar, Rats, Glucagon-Like Peptide 1, Glucagon-Like Peptide 2
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