Electrogenic glucose sensor of neuromuscular junction

描述(由申请人提供)：最近，一系列关键的实验从钠-葡萄糖共转运体(SGLT)家族中鉴定出一种假定的人类葡萄糖传感器。本研究证实SGLT 3型(SGLT3)在人类神经肌肉接头处表达，并利用非洲爪哇卵母细胞的电生理研究证明，人SGLT3通过转运Na+而不是葡萄糖来调节膜电位对葡萄糖的响应。这项研究旨在通过分析神经肌肉接头内源性SGLT3对葡萄糖的电生反应，并评估这些反应对骨骼肌的调制作用，来扩展这项研究。具体地说，本研究将阐明SLGT3底物的特异性，建立一个研究内源性SGLT3的神经肌肉模型，并研究SGLT3在神经肌肉接头处介导的葡萄糖诱导的作用以及对骨骼肌功能的影响。了解SGLT3的生理作用可能有助于我们理解人体骨骼肌对营养物质的调节、葡萄糖的感知以及与糖平衡紊乱相关的疾病，如糖尿病。

DESCRIPTION (provided by applicant): Recently, a pivotal series of experiments identified a putative human glucose sensor from the sodium-glucose cotransporter (SGLT) family. This study identified that SGLT type 3 (SGLT3) is expressed at the human neuromuscular junction and used electrophysiological studies in Xenopus laevis oocytes to demonstrate that human SGLT3 modulates the membrane potential in response to glucose by transporting Na+, but not glucose. The research in this proposal aims to extend this study by analyzing the electrogenic responses to glucose by endogenous SGLT3 at the neuromuscular junction and assessing the modulatory effect these responses will have on skeletal muscle. Specifically, this research will elucidate SLGT3 substrate specificity, identify an established neuromuscular model to study endogenous SGLT3 and characterize the glucose-induced effects of mediated by SGLT3 at the neuromuscular junction and on skeletal muscle function. Understanding the physiological role of SGLT3 may significantly contribute to our understanding of human skeletal muscle regulation by nutrients, glucose sensing and diseases associated with the disruption of glucose homeostasis, such as diabetes mellitus.