Repository logo
 

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

Published version
Peer-reviewed

Change log

Authors

Roberts, Geoffrey P 
McGavigan, Anne K 
Kay, Richard G 
Li, Joyce 

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.

Description

Keywords

GLP-1, bariatric surgery, enteroendocrine cells, gut hormones, intestinal transit, mass spectrometry, peptidomics, transcriptomics, Adult, Animals, Bariatric Surgery, Enteroendocrine Cells, Female, Glucagon-Like Peptide 1, Glucose, Homeostasis, Humans, Hypoglycemic Agents, Insulin Secretion, Intestinal Mucosa, Male, Mice, Mice, Inbred C57BL, Middle Aged, Obesity, Peptide Fragments, Peptide YY, Postoperative Period, Transcriptome

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

26

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/3)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (106262/Z/14/Z)
European Foundation for the Study of Diabetes (EFSD) (unknown)
Royal College of Surgeons of England (unknown)
Medical Research Council (MC_UU_12012/1)
Medical Research Council (MR/M009041/1)
Medical Research Council (MR/M024873/1)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)
RNA-sequencing was undertaken at the CRUK Cambridge Institute Genomics Core. Cell sorting was performed at the NIHR Cambridge BRC Cell Phenotyping Hub. PL received a Society for Endocrinology Early Career Grant. GR received an Addenbrooke’s Charitable Trust / Evelyn Trust Cambridge Clinical Research Fellowship [16-69] and a Royal College of Surgeons Research Fellowship. The work was partially funded by a project grant from the EFSD/Novo Nordisk Programme for Diabetes Research in Europe.