胰高血糖素样肽-1
医学
受体
肠内分泌细胞
神经科学
外围设备
赛马鲁肽
神经元
内科学
内分泌学
胰高血糖素样肽1受体
生物
利拉鲁肽
兴奋剂
内分泌系统
激素
糖尿病
2型糖尿病
作者
Daniel I. Brierley,Marie K. Holt,Avninder Singh,Alan de Araujo,Molly McDougle,Macarena Vergara,Majd H. Afaghani,Shin-Jae Lee,Karen A. Scott,Calyn B. Maske,Wolfgang Langhans,Eric G. Krause,Annette D. de Kloet,Fiona M. Gribble,Frank Reimann,Linda Rinaman,Guillaume de Lartigue,Stefan Trapp
标识
DOI:10.1038/s42255-021-00344-4
摘要
The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which, respectively, define the peripheral and central GLP-1 systems. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut-brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Here we show that PPGNTS neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPGNTS neurons predominantly receive vagal input from oxytocin-receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPGNTS neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPGNTS neuron activation suppresses eating more potently than semaglutide alone. We conclude that central and peripheral GLP-1 systems suppress eating via independent gut-brain circuits, providing a rationale for pharmacological activation of PPGNTS neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy.
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