Lactaturia and loss of sodium-dependent lactate uptake in the colon of SLC5A8-deficient mice.
SLC5A8 is a member of the sodium/glucose cotransporter family. It has been proposed that SLC5A8 might act as an apical iodide transporter in the thyroid follicular cells or as a transporter of short chain monocarboxylates. We have directly addressed the functional role of SLC5A8 in vivo by generation of SLC5A8 mutant mice. We found that SLC5A8 is responsible for the re-absorption of lactate at the apical membrane of the kidney proximal tubules and of serous salivary gland ducts. In addition, SLC5A8 mediated the uptake of lactate into colonocytes under physiological conditions. We did not find any evidence of SLC5A8 being essential for the apical iodide transport in the thyroid gland, even if the ion-cotransporter SLC26A4, causing the human Pendred syndrome, is missing. Because SLC5A8 is transcriptionally silenced in many tumors, it has been proposed that SLC5A8-mediated transport of butyrate suppresses tumor formation. Treatment of Slc5a8(-/-) mice with carcinogens and breeding to the Apc(min) mouse line did not reveal a higher incidence of tumor formation. We conclude that SLC5A8 is instrumental in preventing lactaturia and loss of sodium-dependent uptake of lactate in the colon but does not have any apparent role in the prevention of tumor formation and growth.
Department of Cardiac Development and Remodelling, Max-Planck-Institut fuer Herzund Lungenforschung, Parkstrasse 1, D-61231 Bad Nauheim, Germany.
Henning
H
Frank
Nicole
N
Gröger
Martin
M
Diener
Christoph
C
Becker
Thomas
T
Braun
Thomas
T
Boettger
D000818:Animals; D002087:Butyrates / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D007408:Intestinal Absorption / Q000187:drug effects / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics / Q000473:pathology / Q000652:urine*; D019344:Lactic Acid / Q000652:urine*; D051379:Mice; D018345:Mice, Knockout; D027501:Monocarboxylic Acid Transporters; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D002087:Butyrates; D002273:Carcinogens; D027682:Cation Transport Proteins; D027501:Monocarboxylic Acid Transporters; C507459:Slc5a8 protein, mouse; D019344:Lactic Acid; D012964:Sodium