Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery
Larraufie, Pierre ; Roberts, Geoffrey P. ; McGavigan, Anne K. ; Kay, Richard G. ; Li, Hui Joyce ; Leiter, Andrew B. ; Melvin, Audrey ; Biggs, Emma K. ; Ravn, Peter ; Davy, Kathleen ... show 5 more
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Keywords
bariatric surgery
enteroendocrine cells
gut hormones
intestinal transit
mass spectrometry
peptidomics
transcriptomics
Digestive System
Endocrine System Diseases
Endocrinology
Hormones, Hormone Substitutes, and Hormone Antagonists
Nutritional and Metabolic Diseases
Surgical Procedures, Operative
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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.
Source
Cell Rep. 2019 Feb 5;26(6):1399-1408.e6. doi: 10.1016/j.celrep.2019.01.047. Link to article on publisher's site