Abstract：
OBJECTIVE: Glucagon is a critical hormone regulating glucose metabolism. It stimulates the liver to release glucose under low blood sugar conditions, thereby maintaining blood glucose stability. Excessive glucagon secretion and hyperglycemia is observed in individuals with diabetes. Precise modulation of glucagon is significant to maintain glucose homeostasis. Piezo1 is a mechanosensitive ion channel capable of converting extracellular mechanical forces into intracellular signals, thus regulating hormonal synthesis and secretion. This study aims to investigate the role of Piezo1 in regulating glucagon production in α cells.
METHODS: The effects of Piezo1 on glucagon production were examined in normal- or high-fat diet fed α cell-specific Piezo1 knockout mice (Gcg-Piezo1-/-), and the murine pancreatic α cell line αTC1-6. Expression of Proglucagon was investigated by real-time PCR and western blotting. Plasma glucagon and insulin were detected by enzyme immunoassay.
RESULTS: Under both normal- and high-fat diet conditions, Gcg-Piezo1-/- mice exhibited increased pancreatic α cell proportion, hyperglucagonemia, impaired glucose tolerance, and activated pancreatic mTORC1 signaling. Activation of Piezo1 by its agonist Yoda1 or overexpression of Piezo1 led to decreased glucagon synthesis and suppressed mTOR signaling pathway in αTC1-6 cells. Additionally, the levels of glucagon in the medium were also reduced. Conversely, knockdown of Piezo1 produced opposite effects.
CONCLUSIONS: Our study uncovers the regulatory role of the Piezo1 ion channel in α cells. Piezo1 influences glucagon production by affecting mTOR signaling pathway.
METHODS: The effects of Piezo1 on glucagon production were examined in normal- or high-fat diet fed α cell-specific Piezo1 knockout mice (Gcg-Piezo1-/-), and the murine pancreatic α cell line αTC1-6. Expression of Proglucagon was investigated by real-time PCR and western blotting. Plasma glucagon and insulin were detected by enzyme immunoassay.
RESULTS: Under both normal- and high-fat diet conditions, Gcg-Piezo1-/- mice exhibited increased pancreatic α cell proportion, hyperglucagonemia, impaired glucose tolerance, and activated pancreatic mTORC1 signaling. Activation of Piezo1 by its agonist Yoda1 or overexpression of Piezo1 led to decreased glucagon synthesis and suppressed mTOR signaling pathway in αTC1-6 cells. Additionally, the levels of glucagon in the medium were also reduced. Conversely, knockdown of Piezo1 produced opposite effects.
CONCLUSIONS: Our study uncovers the regulatory role of the Piezo1 ion channel in α cells. Piezo1 influences glucagon production by affecting mTOR signaling pathway.
摘要：
目的：胰高血糖素是一种调节糖代谢的关键激素。它刺激肝脏在低血糖条件下释放葡萄糖，从而维持血糖稳定性。在患有糖尿病的个体中观察到过度的胰高血糖素分泌和高血糖症。胰高血糖素的精确调节对于维持葡萄糖稳态是重要的。Piezo1是一种机械敏感性离子通道，能够将细胞外机械力转化为细胞内信号，从而调节荷尔蒙的合成和分泌。本研究旨在探讨Piezo1在调节α细胞胰高血糖素产生中的作用。
方法：在正常或高脂饮食喂养α细胞特异性Piezo1敲除小鼠（Gcg-Piezo1-/-）中检查了Piezo1对胰高血糖素产生的影响，和鼠胰腺α细胞系αTC1-6。通过实时PCR和蛋白质印迹研究胰高血糖素原的表达。酶免疫法检测血浆胰高血糖素和胰岛素。
结果：在正常和高脂饮食条件下，Gcg-Piezo1-/-小鼠胰腺α细胞比例增加，高胰高血糖素血症,糖耐量受损,和激活胰腺mTORC1信号。Piezo1通过其激动剂Yoda1或Piezo1的过表达激活导致αTC1-6细胞中胰高血糖素合成减少并抑制mTOR信号通路。此外,培养基中胰高血糖素的水平也降低。相反，击倒Piezo1产生相反的效果。
结论：我们的研究揭示了Piezo1离子通道在α细胞中的调节作用。Piezo1通过影响mTOR信号通路影响胰高血糖素的产生。
方法：在正常或高脂饮食喂养α细胞特异性Piezo1敲除小鼠（Gcg-Piezo1-/-）中检查了Piezo1对胰高血糖素产生的影响，和鼠胰腺α细胞系αTC1-6。通过实时PCR和蛋白质印迹研究胰高血糖素原的表达。酶免疫法检测血浆胰高血糖素和胰岛素。
结果：在正常和高脂饮食条件下，Gcg-Piezo1-/-小鼠胰腺α细胞比例增加，高胰高血糖素血症,糖耐量受损,和激活胰腺mTORC1信号。Piezo1通过其激动剂Yoda1或Piezo1的过表达激活导致αTC1-6细胞中胰高血糖素合成减少并抑制mTOR信号通路。此外,培养基中胰高血糖素的水平也降低。相反，击倒Piezo1产生相反的效果。
结论：我们的研究揭示了Piezo1离子通道在α细胞中的调节作用。Piezo1通过影响mTOR信号通路影响胰高血糖素的产生。
