Physiology, Monash University, 3800 Clayton, Australia.
J Neuroendocrinol. 2013 Jul;25(7):597-604. doi: 10.1111/jne.12039.
The central glucagon-like peptide (GLP)-1 receptor mediates a number of metabolic processes, including feeding, body weight and glucose homeostasis. More recently, roles in energy expenditure and reward pathway modulation have been described. GLP-1 receptor agonism promotes insulin release and is currently used to treat type 2 diabetes humans, with a common side effect being weight loss. It is likely that many of these metabolic effects are mediated by GLP-1Rs located in the central nervous system, throughout areas known to be important in control of energy homeostasis. The physiological role of the GLP-1 receptor signalling in each of these brain nuclei is becoming clearer and the GLP-1 system appears to act as an integrator of peripheral energy availability and effector of metabolic regulation. This makes it an attractive target for obesity therapies, with excellent pre-clinical efficacy seen in molecules combining GLP-1 receptor agonism with glucagon receptor agonism. This review discusses what is known about the functions of the GLP-1 receptor in the central nervous system, and highlights the ways that this system may be targeted for development of new obesity therapeutics.
中央胰高血糖素样肽 (GLP)-1 受体介导许多代谢过程，包括进食、体重和葡萄糖稳态。最近，还描述了其在能量消耗和奖励途径调节中的作用。GLP-1 受体激动剂可促进胰岛素释放，目前用于治疗 2 型糖尿病患者，常见的副作用是体重减轻。很可能这些代谢作用中的许多都是由中枢神经系统中的 GLP-1R 介导的，这些区域在控制能量稳态方面起着重要作用。GLP-1 受体信号在这些脑核中的每一个的生理作用变得更加清晰，GLP-1 系统似乎作为外周能量可用性的整合器和代谢调节的效应器。这使其成为肥胖症治疗的有吸引力的靶点，具有良好的临床前疗效的分子将 GLP-1 受体激动剂与胰高血糖素受体激动剂结合使用。本文讨论了中枢神经系统中 GLP-1 受体的功能，强调了针对该系统开发新的肥胖症治疗方法的途径。
