[PDF][PDF] Important role of the GLP-1 axis for glucose homeostasis after bariatric surgery

P Larraufie, GP Roberts, AK McGavigan, RG Kay, J Li… - Cell reports, 2019 - cell.com
P Larraufie, GP Roberts, AK McGavigan, RG Kay, J Li, A Leiter, A Melvin, EK Biggs, P Ravn…
Cell reports, 2019cell.com
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 …
Summary
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.
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