Institute of Veterinary Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zurich, Switzerland.
Physiol Behav. 2010 Jul 14;100(5):511-8. doi: 10.1016/j.physbeh.2010.03.001. Epub 2010 Mar 11.
Amylin is secreted by pancreatic beta-cells and is believed to be a physiological signal of satiation. Amylin's effect on eating has been shown to be mediated via a direct action at the area postrema (AP) via amylin receptors that are heterodimers of the calcitonin receptor core protein with a receptor activity modifying protein. Peripheral amylin leads to accumulation of cyclic guanosine monophosphate, phosphorylated extracellular-signal regulated kinase 1/2 and c-Fos protein in AP neurons. The particular amylin-activated AP neurons mediating its anorexigenic action seem to be noradrenergic. The central pathways mediating amylin's effects have been characterized by lesioning and tracing studies, identifying important connections from the AP to the nucleus of the solitary tract and lateral parabrachial nucleus. Amylin was shown to interact, probably at the brainstem, with other signals involved in the short term control of food intake, namely cholecystokinin, glucagon-like peptide 1 and peptide YY. Amylin also interacts with the adiposity signal leptin; this interaction, which is thought to involve the hypothalamus, may have important implications for the development of new and improved hormonal obesity treatments. In conclusion, amylin actions on food intake seem to reside primarily within the brainstem, and the associated mechanisms are starting to be unraveled. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
胰岛淀粉样多肽由胰腺β细胞分泌,被认为是饱腹感的生理信号。胰岛淀粉样多肽对摄食的影响已被证明是通过其受体在孤束核(NTS)和外侧臂旁核(LPBN)的神经通路介导的。外周胰岛淀粉样多肽导致环鸟苷酸单磷酸、磷酸化细胞外信号调节激酶 1/2 和 c-Fos 蛋白在 AP 神经元中积累。介导其厌食作用的特定胰岛淀粉样多肽激活的 AP 神经元似乎是去甲肾上腺素能神经元。通过损伤和示踪研究,确定了从 AP 到 NTS 和 LPBN 的重要连接,从而对介导胰岛淀粉样多肽作用的中枢途径进行了特征描述。研究表明,胰岛淀粉样多肽与其他参与短期食物摄入控制的信号相互作用,如胆囊收缩素、胰高血糖素样肽 1 和肽 YY。胰岛淀粉样多肽还与肥胖信号瘦素相互作用;这种相互作用,据认为涉及下丘脑,可能对新的和改进的激素肥胖治疗的发展具有重要意义。总之,胰岛淀粉样多肽对食物摄入的作用似乎主要存在于脑干中,相关机制开始被揭示。本文是在 2009 年 7 月波特兰举行的摄食行为学会(SSIB)年会上,作为特邀综述、获奖者或主题演讲发表的。