Electrogenic glucose sensor of neuromuscular junction

神经肌肉接头的电化学葡萄糖传感器

• 批准号: 7210684
• 负责人: Andrew Alvin Voss
• 金额: $ 4.88万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7210684
• 关键词: Animal Model; Antibodies; Binding; Biochemical; Complex; Condition; Coupling; Diabetes Mellitus; Disease; Disruption; Electrodes; Electrophysiology (science); Elevation; Family; Galactose; Glucose; Human; Immunohistochemistry; Insulin-Dependent Diabetes Mellitus; Maintenance; Malabsorption Syndromes; Measurement; Mediating; Membrane; Membrane Potentials; Metabolic Diseases; Modeling; Muscle; Muscle function; Nature; Neuromuscular Junction; Nutrient; Oocytes; Oryctolagus cuniculus; Pancreatic Diseases; Physiological; Process; Range; Rattus; Regulation; Research; Research Proposals; Role; Series; Serum; Skeletal Muscle; Skeletal system; Sodium; Specificity; Substrate Specificity; System; Xenopus laevis; base; blood glucose regulation; extracellular; glucose metabolism; glucose sensor; glucose transport; neuromuscular transmission; research study; response; sugar

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.

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）家族中鉴定出一种假定的人类葡萄糖传感器。这项研究确定了 SGLT 3 型 (SGLT3) 在人类神经肌肉接头处表达，并利用非洲爪蟾卵母细胞的电生理学研究证明，人类 SGLT3 通过转运 Na+ 而不是葡萄糖来响应葡萄糖来调节膜电位。本提案中的研究旨在通过分析神经肌肉接头处内源性 SGLT3 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。具体来说，这项研究将阐明 SLGT3 底物特异性，确定已建立的神经肌肉模型来研究内源性 SGLT3，并表征 SGLT3 在神经肌肉接头处介导的葡萄糖诱导效应和对骨骼肌功能的影响。了解 SGLT3 的生理作用可能会极大地有助于我们了解营养物质、葡萄糖感应以及与葡萄糖稳态破坏相关的疾病（例如糖尿病）对人类骨骼肌的调节。