Blood amino acid levels are maintained in a narrow physiological range. The pancreatic α cells have emerged as the primary aminoacidemia regulator through glucagon secretion to promote hepatic amino acid catabolism. Interruption of glucagon signaling disrupts the liver–α cells axis leading to hyperaminoacidemia, which triggers a compensatory rise in glucagon secretion and α cell hyperplasia. The mechanisms of hyperaminoacidemia-induced α cell hyperplasia remain incompletely understood. Using a mouse α cell line and studies in zebrafish and mice, we found that hyperaminoacidemia-induced α cell hyperplasia requires ErbB3 signaling. In addition to mechanistic target of rapamycin complex 1, another ErbB3 downstream effector signal transducer and activator of transcription 3 also plays a role in α cell hyperplasia. Mechanistically, ErbB3 may partner with ErbB2 to stimulate cyclin D2 and suppress p27 mechanistic target of rapamycin complex 1 and signal transducer and activator of transcription 3. Our study identifies ErbB3 as a new regulator for hyperaminoacidemia-induced α cell proliferation and a critical component of the liver–α cells axis that regulates aminoacidemia.

中文翻译：

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ErbB3 是高氨基酸血症诱导的胰腺 α 细胞增生所必需的


血液氨基酸水平维持在狭窄的生理范围内。胰腺α细胞已成为主要的氨基酸血症调节剂，通过胰高血糖素分泌促进肝脏氨基酸分解代谢。胰高血糖素信号传导的中断会破坏肝-α细胞轴，导致高氨基酸血症，从而引发胰高血糖素分泌和α细胞增生的代偿性增加。高氨基酸血症诱导 ​​α 细胞增生的机制仍不完全清楚。使用小鼠 α 细胞系以及对斑马鱼和小鼠的研究，我们发现高氨基酸血症诱导的 α 细胞增生需要 ErbB3 信号传导。除了雷帕霉素复合物 1 的机制靶标外，另一个 ErbB3 下游效应信号转导子和转录激活子 3 也在 α 细胞增生中发挥作用。从机制上讲，ErbB3 可能与 ErbB2 合作，刺激细胞周期蛋白 D2 并抑制雷帕霉素复合物 1 和信号转导子和转录激活子 3 的 p27 机制靶标。我们的研究确定 ErbB3 是高氨基酸血症诱导的 α 细胞增殖的新调节因子，也是细胞增殖的关键组成部分。调节氨基酸血症的肝-α细胞轴。