Modulating the endogenous stores of gastrointestinal hormones is considered a promising strategy to mimic gut endocrine function, improving metabolic dysfunction. Here, we exploit mouse and human knock-in and knockout intestinal organoids and show that agents used as commercial lipid excipients can activate nutrient-sensitive receptors on enteroendocrine cells (EECs) and, when formulated as lipid nanocarriers, can bestow biological effects through the release of GLP-1, GIP, and PYY from K and L cells. Studies in wild-type, dysglycemic, and gut Gcg knockout mice demonstrated that the effect exerted by lipid nanocarriers could be modulated by varying the excipients (e.g., nature and quantities), the formulation methodology, and their physiochemical properties (e.g., size and composition). This study demonstrates the therapeutic potential of using nanotechnology to modulate release of multiple endogenous hormones from the enteroendocrine system through a patient-friendly, inexpensive, and noninvasive manner.

中文翻译：

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智能控制基于脂质的纳米载体，用于微调肠道激素分泌


调节胃肠道激素的内源性储存被认为是模拟肠道内分泌功能、改善代谢功能障碍的一种有前途的策略。在这里，我们利用小鼠和人类敲入和敲除肠道类器官，并表明用作商业脂质赋形剂的试剂可以激活肠内分泌细胞 （EEC） 上的营养敏感受体，并且当配制成脂质纳米载体时，可以通过从 K 和 L 细胞释放 GLP-1、GIP 和 PYY 来赋予生物效应。对野生型、血糖不良和肠道 Gcg 敲除小鼠的研究表明，脂质纳米载体发挥的作用可以通过改变赋形剂（例如，性质和数量）、制剂方法及其理化性质（例如，大小和组成）来调节。本研究证明了使用纳米技术通过患者友好、廉价和无创的方式调节肠内分泌系统释放多种内源性激素的治疗潜力。