Functional characterisation of human SGLT-5 as a novel kidney-specific sodium-dependent sugar transporter.
Sodium glucose cotransporters (SGLT) actively catalyse carbohydrate transport across cellular membranes. Six of the 12 known SGLT family members have the capacity to bind and/or transport monosaccharides (SGLT-1 to 6); of these, all but SGLT-5 have been characterised. Here we demonstrate that human SGLT-5 is exclusively expressed in the kidney. Four splice variants were detected and the most abundant SGLT-5-mRNA was functionally characterised. SGLT-5 mediates sodium-dependent [(14)C]-α-methyl-D-glucose (AMG) transport that can be inhibited by mannose, fructose, glucose, and galactose. Uptake studies using demonstrated high capacity transport for mannose and fructose and, to a lesser extent, glucose, AMG, and galactose. SGLT-5 mediated mannose, fructose and AMG transport was weakly (μM potency) inhibited by SGLT-2 inhibitors. In summary, we have characterised SGLT-5 as a kidney mannose transporter. Further studies are warranted to explore the physiological role of SGLT-5.
Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach, Germany. rolf.grempler@boehringer-ingelheim.com
Rolf
R
Grempler
Robert
R
Augustin
Stefanie
S
Froehner
Tobias
T
Hildebrandt
Eric
E
Simon
Michael
M
Mark
Peter
P
Eickelmann
D000042:Absorption / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009928:Organ Specificity; D010695:Phlorhizin / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D051269:Sodium-Glucose Transporter 1; D010695:Phlorhizin; D005947:Glucose