The high affinity Na+/glucose cotransporter. Re-evaluation of function and distribution of expression.
1994; Elsevier BV; Volume: 269; Issue: 16 Linguagem: Inglês
10.1016/s0021-9258(17)32677-7
ISSN1083-351X
AutoresWon Suk Lee, Yoshiakira Kanai, Rebecca G. Wells, Matthias A. Hediger,
Tópico(s)Amino Acid Enzymes and Metabolism
ResumoW e report the primary structure, functional characterization, and tissue distribution of the high affinity Na+/glucose cotransporter SGLTl from rat kidney.Rat SGLTl (666 amino acid residues) is 8647% identical to SGLTl from rabbit, pig, and human.High stringency Northern analysis demonstrated that SGLTl is strongly expressed in small intestine and at lower levels in kidney, liver, and lung.In situ hybridization performed on kidney sections revealed that SGLTl is predominantly present in 53 segments of the proximal tubule.In small intestine, SGLTl message was located in cells of the lower two-thirds of intestinal villi.Expression of rat SGLTl in Xenopus oocytes resulted in a large Na+-dependent uptake of ['4C1-a-methyl-~-g~ucopyranoside (cuMeGlc).Overall, the transport characteristics were similar to those of rabbit SGLT1.High affinity Na+/ glucose cotransport in membrane vesicles was previously shown to be coupled to the cotransport of two Na' ions (Turner, R. J., and Moran, A. (1982) J. MembL Biol.70, 3745).Previous kinetic analysis of rat and rabbit SGLT1, however, demonstrated between second and first order dependence of sugar uptake on extracellular Na' concentration, suggesting the existence of Na+-binding sites with different affinities.Here, we directly compared the initial rates of the cuMeGlc uptake with aMeGlc-induced inward currents as an indicator of the Na+ flux.This analysis clearly revealed a Na' to glucose coupling ratio of 2:l.In summary, our data provide important insights into the function and tissue distribution of the high affinity Na+/glucose cotransporter SGLTl and clarify its role in the reabsorption mechanism of D-glucose in the kidney. ~~Two classes of glucose transporters have been described in mammalian cells: Na+-coupled and facilitated glucose transporters.In the small intestine and the proximal tubule of the kidney, absorption of luminal D-glucose against a concentration gradient occurs via epithelial Na+/glucose cotransporters lo-
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