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Cell Rep. 2019 Feb 5;26(6):1399-1408.e6. doi: 10.1016/j.celrep.2019.01.047.

Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery.

Author information

1
Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
2
Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
3
Department of Antibody Discovery and Protein Engineering, MedImmune, Granta Park, Cambridge CB21 6GH, UK.
4
Department of Cardiovascular and Metabolic Disease, MedImmune, Granta Park, Cambridge, UK.
5
Cambridge Oesophago-gastric Centre, Addenbrooke's Hospital, Cambridge, UK.
6
Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. Electronic address: fmg23@cam.ac.uk.

Abstract

Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.

KEYWORDS:

GLP-1; bariatric surgery; enteroendocrine cells; gut hormones; intestinal transit; mass spectrometry; peptidomics; transcriptomics

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