Department of Clinical Biochemistry, Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Diabet Med. 2023 Dec;40(12):e15212. doi: 10.1111/dme.15212. Epub 2023 Sep 15.
Glucagon-like peptide-1 (GLP-1)-based medication is now widely employed in the treatment of type 2 diabetes and obesity. Like other gut hormones, GLP-1 is released from eneteroendocrine cells after a meal and in this review, based on the Dorothy Hodgkin lecture delivered during the annual meeting of Diabetes UK in 2023, I argue that there is sufficient spare capacity of GLP-1 and other gut hormone expressing cells that could be recruited therapeutically. Years of research has revealed several receptors expressed in enteroendocrine cells that could be targeted to stimulate hormone release: although from this research it seems unlikely to find agents that selectively boost GLP-1, release of a mixture of hormones might be the more desirable outcome anyway, given the recent promising results of new peptides combining GLP1-receptor with other gut hormone receptor activation. Alternatively, the fact that GLP-1 and peptideYY (PYY) expressing cells are found in greater density in the ileum might be exploited by increasing the delivery of chyme to the distal small intestine.
胰高血糖素样肽-1（GLP-1）类药物目前广泛用于治疗 2 型糖尿病和肥胖症。与其他肠激素一样，GLP-1 在进食后从肠内分泌细胞释放，在这篇综述中，我基于 2023 年英国糖尿病协会年会上的多萝西·霍奇金演讲，认为 GLP-1 和其他表达肠激素的细胞有足够的备用能力，可以进行治疗性招募。多年的研究揭示了几种在肠内分泌细胞中表达的受体，这些受体可以被靶向以刺激激素释放：尽管从这项研究中似乎不太可能找到选择性增强 GLP-1 释放的药物，但无论如何，释放混合激素可能是更理想的结果，因为最近新的肽类药物将 GLP1 受体与其他肠激素受体激活相结合的结果令人鼓舞。或者，由于回肠中 GLP-1 和肽 YY（PYY）表达细胞的密度更高，可以通过增加食糜向远端小肠的输送来利用这一事实。
