Gribble, F., et al. Important role of the GLP-1 axis for glucose homeostasis after bariatric surgery, 26(6) 1399-1408
Bariatric surgery is widely used to treat obesity, and additionally 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 hotly debated. Here we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1R) 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, but 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.