Electrogenic glucose sensor of neuromuscular junction

描述（由申请人提供）：最近，一系列关键实验从钠-葡萄糖协同转运蛋白（SGLT）家族中鉴定出一种推定的人葡萄糖传感器。本研究确定了SGLT 3型（SGLT 3）在人神经肌肉接头处表达，并使用非洲爪蟾卵母细胞的电生理学研究证明了人SGLT 3通过转运Na+（而非葡萄糖）调节膜电位以响应葡萄糖。本提案中的研究旨在通过分析神经肌肉接头处内源性SGLT 3对葡萄糖的生电反应并评估这些反应对骨骼肌的调节作用来扩展本研究。具体而言，本研究将阐明SLGT 3底物特异性，确定用于研究内源性SGLT 3的已建立神经肌肉模型，并表征神经肌肉接头处和骨骼肌功能中SGLT 3介导的葡萄糖诱导效应。了解SGLT 3的生理作用可能有助于我们了解营养素对人体骨骼肌的调节、葡萄糖感知以及与葡萄糖稳态破坏相关的疾病（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.