de Sousa Erica, Sparks Lauren, Townsend Kristy
Department of Neurological Surgery, College of Medicine, The Ohio State University, Columbus, OH.
Translational Research Institute, AdventHealth, Orlando, FL.
Diabetes. 2025 Aug 1;74(8):1313-1319. doi: 10.2337/db25-0158.
There is currently a revolution in the pharmacologic treatment of obesity and diabetes with newly available agonists of incretin receptors. The health benefits of these novel treatments include not only metabolic effects but also improvements in brain neurodegenerative conditions. Receptors for incretins have been described in the hypothalamic appetite regulatory center; however, their expression in the peripheral nervous system (PNS) has been largely overlooked, despite likely contributing important effects. For example, the PNS is essential for the control of numerous metabolically relevant pathways in tissues such as liver, adipose, intestine, and muscle, and incretin receptors are found on nerves innervating some, if not all, of these metabolically important tissues. In this article, we summarize the knowledge to date regarding incretin receptors and incretin drug actions in the PNS, as well as PNS control over incretin release, and the related implications for metabolic disease states that are accompanied by peripheral neuropathy.
The peripheral nervous system controls gut glucagon-like peptide 1 (GLP-1) release through enteric and sympathetic neurons. Sensory, motor, and enteric neurons express GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, and vagal neurons express the GLP-1 receptor only. GLP-1 and GIP receptors are expressed in both murine and human adipose tissue nerves and Schwann cells. Available data indicate incretin drugs are a promising novel treatment for peripheral nerve diseases. The differential pharmacodynamic properties of incretin drugs should be explored further in the prevention and treatment of metabolic disease-associated peripheral nerve degeneration.
目前，随着新型肠促胰岛素受体激动剂的出现，肥胖和糖尿病的药物治疗正在经历一场变革。这些新型治疗方法的健康益处不仅包括代谢效应，还包括改善脑部神经退行性疾病。肠促胰岛素受体已在下丘脑食欲调节中心被描述；然而，尽管其可能具有重要作用，但其在周围神经系统（PNS）中的表达在很大程度上被忽视了。例如，PNS对于控制肝脏、脂肪、肠道和肌肉等组织中众多与代谢相关的途径至关重要，并且在支配这些代谢重要组织中部分（如果不是全部）组织的神经上发现了肠促胰岛素受体。在本文中，我们总结了迄今为止关于PNS中肠促胰岛素受体和肠促胰岛素药物作用的知识，以及PNS对肠促胰岛素释放的控制，以及对伴有周围神经病变的代谢疾病状态的相关影响。
周围神经系统通过肠神经元和交感神经元控制肠道胰高血糖素样肽1（GLP - 1）的释放。感觉神经元、运动神经元和肠神经元表达GLP - 1和葡萄糖依赖性促胰岛素多肽（GIP）受体，而迷走神经神经元仅表达GLP - 1受体。GLP - 1和GIP受体在小鼠和人类脂肪组织神经以及雪旺细胞中均有表达。现有数据表明，肠促胰岛素药物是治疗周围神经疾病的一种有前景的新型疗法。在预防和治疗与代谢疾病相关的周围神经变性方面，应进一步探索肠促胰岛素药物的不同药效学特性。
