下丘脑T1R2/T1R3神经元在调控甜味觉感知及葡萄糖稳态中的作用及机制

Glucose homeostasis is vital to the survival and development of the animals. Hypothalamic glucose-sensitive neurons expressing T1R2/T1R3 detect directly the glucose level in the brain through the mechanism similar to the sweet signal transduction. Many previous studies have testified that leptin plays an important role in the modulating glucose homeostasis, while we havn’t clarified whether hypothalamic T1R2/T1R3 neurons modulate glucose homeostasis through regulating the sweet taste perception, whether leptin participate in the modulatory process. This project is designed, by using behavioral, patch clamp technique, immuno-fluorescent staining and molecular biological methods in the Sprague Dawley (SD) rats, to investigate the roles of hypothalamic neurons expressing T1R2/T1R3.in modulating glucose homeostasis through regulating the sweet taste perception, feeding behavior and glycometabolism, to analyze the role of leptin in the modulatory process, to test whether Pro-opiomelanocortin (POMC) neurons in the ARC involve in the modulation. The goals of the present investigation are to explore the hypothalamic mechanisms of glucose hemeostasis modulation at the integrative,.cellular and molecular levels, and to provide valuable data for further studies on the interactions between sweet taste perception, ingestive behavior and homeostasis.

葡萄糖稳态是动物生存和发育的基础，下丘脑表达T1R2/T1R3 的神经元通过类似甜味觉感知的机制，直接感受脑内的葡萄糖水平。瘦素leptin在调控机体的葡萄糖稳态中发挥重要作用，但下丘脑T1R2/T1R3 神经元是否通过影响甜味觉感知来发挥调控葡萄糖稳态的作用，leptin 在这一调控作用中扮演的角色都尚不清楚。本项目拟采用行为学、膜片钳技术、免疫荧光标记、分子生物学等方法，探讨下丘脑T1R2/T1R3 神经元是否通过调控机体的甜味觉感知，摄入行为及糖代谢，参与葡萄糖稳态的维持；分析下丘脑leptin 在这一调控过程中扮演的角色；初步探索下丘脑阿片黑皮质素原(Pro-opiomelanocortin，POMC) 神经元是否参与介导上述调制过程。本研究力图从整体、细胞和分子水平，部分揭示葡萄糖稳态调控的下丘脑机制，并为深入探讨甜味觉感知、摄食行为与内环境稳态的相互作用提供有价值的研究资料。