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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK072818-02
Application #
7210684
Study Section
Special Emphasis Panel (ZRG1-F03B-G (20))
Program Officer
Hyde, James F
Project Start
2006-05-01
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
2
Fiscal Year
2007
Total Cost
$48,796
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Hummel, Charles S; Lu, Chuan; Loo, Donald D F et al. (2011) Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol 300:C14-21
Voss, Andrew A (2009) Extracellular ATP inhibits chloride channels in mature mammalian skeletal muscle by activating P2Y1 receptors. J Physiol 587:5739-52
Voss, Andrew A; Diez-Sampedro, Ana; Hirayama, Bruce A et al. (2007) Imino sugars are potent agonists of the human glucose sensor SGLT3. Mol Pharmacol 71:628-34