Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery
Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery
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DOI：
10.1016/j.celrep.2019.01.047
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发表时间：
2019-02-05
期刊：
影响因子：
8.8
通讯作者：
Gribble, Fiona M.
中科院分区：
文献类型：
--
作者：
Larraufie, Pierre;Roberts, Geoffrey P.;Gribble, Fiona M.
减肥手术广泛用于治疗肥胖症，并以超出预期的体重减轻程度改善2型糖尿病。广泛报道胰高血糖素样肽 1 (GLP-1)、肽 YY (PYY) 和胰岛素餐后浓度升高，但 GLP-1 在减肥后生理学中的重要性仍存在争议。在这里，我们证明 GLP-1 是减肥手术后胰岛素分泌的主要驱动因素，正如使用 Exendin-9 在瘦人中或使用抗 GLP1R 抗体在小鼠中阻断胃切除术后的 GLP-1 受体 (GLP1R) 所证明的那样。转录组学和肽组学分析表明，人和小鼠的肠内分泌细胞在手术后没有改变；相反，我们发现血浆 GLP-1 和 PYY 升高与小鼠远端肠道营养输送增加相关。我们得出的结论是，减肥手术后 GLP-1 分泌增加是由于营养物质快速输送到远端肠道所致，是胰岛素分泌增强的关键驱动因素。
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.