Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
Peptides. 2020 Mar;125:170194. doi: 10.1016/j.peptides.2019.170194. Epub 2019 Nov 4.
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone released from the epithelium of the upper small intestine. While GIP shares common actions on the pancreatic beta cell with glucagon-like peptide-1 (GLP-1), unlike GLP-1, GIP presents a complex target for the development of diabetes and obesity therapies due to its extra-pancreatic effects on fat mass. Recent pharmacological developments, however, have provided insight into a previously unrecognized role for GIP receptor (GIPR) signaling in regulating appetite. Additionally, GIP-based therapeutics have demonstrated promising neuroprotective properties. Together these observations identify an important central component of the GIP/GIPR signaling axis, and have triggered a resurgence of research interest into the central actions of GIP. In this review, we discuss what is currently known about where GIP may act in the central nervous system (CNS), the characteristics of its target cell populations, and the physiological effects of manipulating the activity Gipr-expressing cells in the brain.
葡萄糖依赖性胰岛素多肽（GIP）是从小肠上段上皮细胞释放的肠促胰岛素激素。虽然 GIP 与胰高血糖素样肽-1（GLP-1）对胰腺β细胞具有共同作用，但与 GLP-1 不同，由于 GIP 对脂肪量具有额外的胰腺外作用，因此它是开发糖尿病和肥胖症治疗方法的复杂靶标。然而，最近的药理学发展提供了对 GIP 受体（GIPR）信号在调节食欲中的先前未被认识到的作用的深入了解。此外，基于 GIP 的治疗方法已显示出有希望的神经保护特性。这些观察结果共同确定了 GIP/GIPR 信号轴的一个重要中枢组成部分，并引发了对 GIP 中枢作用的研究兴趣的复兴。在这篇综述中，我们讨论了目前已知的 GIP 可能在中枢神经系统（CNS）中发挥作用的位置、其靶细胞群体的特征，以及操纵大脑中表达 Gipr 的细胞活性的生理效应。
