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

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.
Authors	Pierre Larraufie, Geoffrey P Roberts, Anne K McGavigan, Richard G Kay, Joyce Li, Andrew Leiter, Audrey Melvin, Emma K Biggs, Peter Ravn, Kathleen Davy, David C Hornigold, Giles S H Yeo, Richard H Hardwick, Frank Reimann, Fiona M Gribble
Journal	Cell reports (Cell Rep) Vol. 26 Issue 6 Pg. 1399-1408.e6 (02 05 2019) ISSN: 2211-1247 [Electronic] United States
PMID	30726726 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References	Hypoglycemic Agents Peptide Fragments Peptide YY exendin (9-39) Glucagon-Like Peptide 1 Glucose
Topics	Adult Animals Bariatric Surgery Enteroendocrine Cells (metabolism) Female Glucagon-Like Peptide 1 (blood, metabolism) Glucose (metabolism) Homeostasis Humans Hypoglycemic Agents (adverse effects, therapeutic use) Insulin Secretion Intestinal Mucosa (metabolism) Male Mice Mice, Inbred C57BL Middle Aged Obesity (drug therapy, metabolism, surgery) Peptide Fragments (adverse effects, therapeutic use) Peptide YY (metabolism) Postoperative Period Transcriptome

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