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

Cell reports | 2019

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.

Pubmed ID: 30726726 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK110614
  • Agency: Wellcome Trust, United Kingdom
    Id: 106263/Z/14/Z
  • Agency: Wellcome Trust, United Kingdom
    Id: 106262/Z/14/Z
  • Agency: Wellcome Trust, United Kingdom
    Id: 100574/Z/12/Z
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00014/5
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12012/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/M024873/1
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12012/5
  • Agency: Medical Research Council, United Kingdom
    Id: MR/M009041/1
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12012/3
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00014/3

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