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Facilitative glucose transporter 9, a unique hexose and urate transporter
Manuel Doblado1, Kelle H Moley
1Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
American Journal of Physiology. Endocrinology and Metabolism
|October 3, 2009
Summary
Glucose transporter type 9 (GLUT9) is a novel transporter that also carries uric acid. Genetic links between GLUT9 and serum uric acid levels suggest its role in metabolic diseases and gout.
Area of Science:
- Molecular Biology
- Human Genetics
- Metabolic Diseases
Background:
- GLUT9 is a glucose transporter with two splice variants, GLUT9a and GLUT9b, found in various tissue epithelia.
- These variants exhibit differential localization in polarized cells, with GLUT9a on basolateral and GLUT9b on apical surfaces.
- GLUT9 expression is modulated by glucose availability, increasing under hyperglycemic conditions and decreasing during starvation.
Purpose of the Study:
- To investigate the role of GLUT9 as a uric acid transporter.
- To explore the correlation between GLUT9 genetic variations and serum uric acid levels.
- To understand GLUT9's potential involvement in metabolic syndrome, gout, and fructose metabolism.
Main Methods:
- Analysis of GLUT9 splice variants and their tissue distribution.
- Assessment of GLUT9's substrate specificity, including hexose sugars and uric acid.
- Review of human genetic studies linking GLUT9 single nucleotide polymorphisms (SNPs) to serum uric acid levels.
Main Results:
- GLUT9 demonstrates a unique dual function as a glucose and high-capacity uric acid transporter.
- Significant correlations were identified between GLUT9-mapped SNPs and serum uric acid levels across multiple human cohorts.
- GLUT9 is expressed in articular cartilage, suggesting a role in gout pathogenesis.
Conclusions:
- GLUT9 plays a critical role in uric acid transport and is implicated in hyperuricemia.
- Genetic variations in GLUT9 are associated with serum uric acid levels, highlighting its clinical significance.
- GLUT9 may be a key factor in the pathogenesis of metabolic syndrome, obesity, diabetes, and gout.
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