清华大学王一国等取得重要工作进展。他们研究揭示了famsin胰高血糖素轴介导的葡萄糖稳态。相关研究成果2024年12月19日在线发表于《细胞—代谢》杂志上。

据介绍，胰高血糖素对葡萄糖稳态至关重要，其失调与糖尿病有关。尽管进行了广泛的研究，但控制胰高血糖素分泌的机制仍不完全清楚。

研究人员揭示了famsin，一种肠道分泌的激素，促进胰高血糖素释放并调节葡萄糖稳态。从机制上讲，famsin在小鼠体内与其受体OLFR796结合（在人类中为OR10P1），启动胰岛α细胞内质网中的钙释放。这一过程会触发胰高血糖素的分泌，从而通过胰高血糖激素信号传导促进肝脏葡萄糖的产生。

此外，famsin信号传导的缺乏会减少肝脏葡萄糖的产生并降低血糖水平，这突显了famsin胰高血糖素轴在葡萄糖稳态中的重要性。因此，这一研究结果证明了famsin是胰高血糖素分泌的关键调节因子，并为维持葡萄糖稳态的复杂的肠道-胰岛-肝脏间相互作用，提供了有价值的见解。

附：英文原文

Title: A famsin-glucagon axis mediates glucose homeostasis

Author: Aijun Long, Yazhuo Wang, Yihua Guo, Jie Hong, Guang Ning, Zhuoxian Meng, Jiqiu Wang, Yiguo Wang

Issue&Volume: 2024-12-19

Abstract: Glucagon is essential for glucose homeostasis, and its dysregulation is associated with diabetes. Despite extensive research, the mechanisms governing glucagon secretion remain incompletely understood. Here, we unveil that famsin, a gut-secreted hormone, promotes glucagon release and modulates glucose homeostasis. Mechanistically, famsin binds to its receptor OLFR796 in mice (OR10P1 in humans), initiating calcium release in the endoplasmic reticulum of islet α cells. This process triggers glucagon secretion, consequently promoting hepatic glucose production through glucagon signaling. Furthermore, deficiency of famsin signaling reduces hepatic glucose production and lowers blood glucose levels, underscoring the significance of the famsin-glucagon axis in glucose homeostasis. Therefore, our findings establish famsin as a crucial regulator of glucagon secretion and provide valuable insights into the intricate gut-islet-liver interorgan crosstalk that maintains glucose homeostasis.

DOI: 10.1016/j.cmet.2024.11.008

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00454-6