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.

中文翻译：

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famsin-胰高血糖素轴介导葡萄糖稳态


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。在这里，我们揭示了 famsin，一种肠道分泌的激素，促进胰高血糖素的释放并调节葡萄糖稳态。从机制上讲，famsin 与小鼠的受体 OLFR796 （人类的 OR10P1） 结合，启动胰岛α细胞内质网中的钙释放。这个过程触发胰高血糖素分泌，从而通过胰高血糖素信号传导促进肝葡萄糖的产生。此外，famsin 信号转导的缺乏会减少肝脏葡萄糖的产生并降低血糖水平，强调了 famsin-胰高血糖素轴在葡萄糖稳态中的重要性。因此，我们的研究结果将 famsin 确定为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肠-胰岛-肝脏器官间串扰提供了有价值的见解。