Electrogenic glucose sensor of neuromuscular junction

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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.