牛津大学David J. Hodson小组的一项最新研究认为局部GLP1受体预内化指导胰腺α细胞与β细胞之间的通讯。该项研究成果发表在2025年7月14日出版的《细胞—代谢》上。

研究人员发现胰高血糖素样肽-1受体（GLP1R）作为纳米结构域富集在与α细胞接触的β细胞膜上，与增加的单分子转录物表达保持一致。在低糖条件下，靠近α细胞的β细胞通过预内化GLP1R直接感知微摩尔胰高血糖素的释放。预内化的GLP1R与早期β细胞对高葡萄糖的Ca²⁺反应有关，然后在胰岛上传播。相邻的细胞比相邻的细胞分泌更多。局域GLP1R信号在体内和体外都存在，在餐后状态下起作用，代谢应激时β细胞和α细胞之间的GLP1R接触减少。他们详细介绍了胰高血糖素调节胰岛素释放的调控途径。

据介绍，胰腺细胞通过释放胰高血糖素以旁分泌方式调节细胞功能。然而，详细的分子结构背后的α - β细胞调节仍然缺乏表征。

附：英文原文

Title: Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication

Author: Jason C.L. Tong, Charlotte Frazer-Morris, Ali H. Shilleh, Katrina Viloria, Anne de Bray, Adithya Muraleedaran Nair, Paul R.V. Johnson, Rebecca Spiers, Ahmad Kobiita, Oladapo E. Olaniru, Shanta J. Persaud, Robert Hauffe, André Kleinridders, Carsten Schultz, C. Bruce Verchere, Canqi Cui, Jonathan E. Campbell, Malgorzata Cyranka, Alexey Epanchintsev, Carina mml, Johannes Broichhagen, David J. Hodson

Issue&Volume: 2025-07-14

Abstract: Pancreatic alpha cells modulate beta cell function in a paracrine manner through the release of glucagon. However, the detailed molecular architecture underlying alpha-to-beta cell regulation remains poorly characterized. Here, we show that the glucagon-like peptide-1 receptor (GLP1R) is enriched as nanodomains on beta cell membranes that contact alpha cells, in keeping with increased single-molecule transcript expression. At low glucose, beta cells next to alpha cells directly sense micromolar glucagon release by pre-internalizing GLP1R. Pre-internalized GLP1R is associated with earlier beta cell Ca2+ responses to high glucose, which are then propagated across the islet. Beta cells adjacent to alpha cells are more secretory than beta cells next to other beta cells. Localized GLP1R signaling occurs in vitro and in vivo, is operative in the post-prandial state, and GLP1R contacts decrease between beta cells and alpha cells during metabolic stress. Thus, we detail a regulated pathway through which glucagon modulates insulin release.

DOI: 10.1016/j.cmet.2025.06.009

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00304-3