Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery.
Published version
Peer-reviewed
Repository URI
Repository DOI
Type
Change log
Authors
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
Journal Title
Conference Name
Journal ISSN
2211-1247
Volume Title
Publisher
Publisher DOI
Sponsorship
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)