The high affinity Na+/glucose cotransporter: Re-evaluation of function and distribution of expression

Wen Sen Lee, Yoshikatsu Kanai, Rebecca G. Wells, Matthias A. Hediger

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

We report the primary structure, functional characterization, and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 from rat kidney. Rat SGLT1 (665 amino acid residues) is 86-87% identical to SGLT1 from rabbit, pig, and human. High stringency Northern analysis demonstrated that SGLT1 is strongly expressed in small intestine and at lower levels in kidney, liver, and lung. In situ hybridization performed on kidney sections revealed that SGLT1 is predominantly present in S3 segments of the proximal tubule. In small intestine, SGLT1 message was located in cells of the lower two-thirds of intestinal villi. Expression of rat SGLT1 in Xenopus oocytes resulted in a large Na+-dependent uptake of [14C]-α-methyl-D-glucopyranoside (αMeGlc). 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. Membr. Biol. 70, 37-45). 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 αMeGlc uptake with αMeGlc-induced inward currents as an indicator of the Na+ flux. This analysis clearly revealed a Na+ to glucose coupling ratio of 2:1. In summary, our data provide important insights into the function and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 and clarify its role in the reabsorption mechanism of D-glucose in the kidney.

Original languageEnglish
Pages (from-to)12032-12039
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number16
Publication statusPublished - Apr 22 1994
Externally publishedYes

Fingerprint

Rats
Glucose
Kidney
Tissue Distribution
Rabbits
Small Intestine
Tissue
Induced currents
Xenopus
Sugars
Liver
Oocytes
In Situ Hybridization
Swine
Binding Sites
Ions
Fluxes
Membranes
Amino Acids
Lung

ASJC Scopus subject areas

  • Biochemistry

Cite this

The high affinity Na+/glucose cotransporter : Re-evaluation of function and distribution of expression. / Lee, Wen Sen; Kanai, Yoshikatsu; Wells, Rebecca G.; Hediger, Matthias A.

In: Journal of Biological Chemistry, Vol. 269, No. 16, 22.04.1994, p. 12032-12039.

Research output: Contribution to journalArticle

Lee, Wen Sen ; Kanai, Yoshikatsu ; Wells, Rebecca G. ; Hediger, Matthias A. / The high affinity Na+/glucose cotransporter : Re-evaluation of function and distribution of expression. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 16. pp. 12032-12039.
@article{0a35e8fb29204baebab42c68fe234dde,
title = "The high affinity Na+/glucose cotransporter: Re-evaluation of function and distribution of expression",
abstract = "We report the primary structure, functional characterization, and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 from rat kidney. Rat SGLT1 (665 amino acid residues) is 86-87{\%} identical to SGLT1 from rabbit, pig, and human. High stringency Northern analysis demonstrated that SGLT1 is strongly expressed in small intestine and at lower levels in kidney, liver, and lung. In situ hybridization performed on kidney sections revealed that SGLT1 is predominantly present in S3 segments of the proximal tubule. In small intestine, SGLT1 message was located in cells of the lower two-thirds of intestinal villi. Expression of rat SGLT1 in Xenopus oocytes resulted in a large Na+-dependent uptake of [14C]-α-methyl-D-glucopyranoside (αMeGlc). 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. Membr. Biol. 70, 37-45). 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 αMeGlc uptake with αMeGlc-induced inward currents as an indicator of the Na+ flux. This analysis clearly revealed a Na+ to glucose coupling ratio of 2:1. In summary, our data provide important insights into the function and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 and clarify its role in the reabsorption mechanism of D-glucose in the kidney.",
author = "Lee, {Wen Sen} and Yoshikatsu Kanai and Wells, {Rebecca G.} and Hediger, {Matthias A.}",
year = "1994",
month = "4",
day = "22",
language = "English",
volume = "269",
pages = "12032--12039",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "16",

}

TY - JOUR

T1 - The high affinity Na+/glucose cotransporter

T2 - Re-evaluation of function and distribution of expression

AU - Lee, Wen Sen

AU - Kanai, Yoshikatsu

AU - Wells, Rebecca G.

AU - Hediger, Matthias A.

PY - 1994/4/22

Y1 - 1994/4/22

N2 - We report the primary structure, functional characterization, and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 from rat kidney. Rat SGLT1 (665 amino acid residues) is 86-87% identical to SGLT1 from rabbit, pig, and human. High stringency Northern analysis demonstrated that SGLT1 is strongly expressed in small intestine and at lower levels in kidney, liver, and lung. In situ hybridization performed on kidney sections revealed that SGLT1 is predominantly present in S3 segments of the proximal tubule. In small intestine, SGLT1 message was located in cells of the lower two-thirds of intestinal villi. Expression of rat SGLT1 in Xenopus oocytes resulted in a large Na+-dependent uptake of [14C]-α-methyl-D-glucopyranoside (αMeGlc). 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. Membr. Biol. 70, 37-45). 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 αMeGlc uptake with αMeGlc-induced inward currents as an indicator of the Na+ flux. This analysis clearly revealed a Na+ to glucose coupling ratio of 2:1. In summary, our data provide important insights into the function and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 and clarify its role in the reabsorption mechanism of D-glucose in the kidney.

AB - We report the primary structure, functional characterization, and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 from rat kidney. Rat SGLT1 (665 amino acid residues) is 86-87% identical to SGLT1 from rabbit, pig, and human. High stringency Northern analysis demonstrated that SGLT1 is strongly expressed in small intestine and at lower levels in kidney, liver, and lung. In situ hybridization performed on kidney sections revealed that SGLT1 is predominantly present in S3 segments of the proximal tubule. In small intestine, SGLT1 message was located in cells of the lower two-thirds of intestinal villi. Expression of rat SGLT1 in Xenopus oocytes resulted in a large Na+-dependent uptake of [14C]-α-methyl-D-glucopyranoside (αMeGlc). 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. Membr. Biol. 70, 37-45). 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 αMeGlc uptake with αMeGlc-induced inward currents as an indicator of the Na+ flux. This analysis clearly revealed a Na+ to glucose coupling ratio of 2:1. In summary, our data provide important insights into the function and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 and clarify its role in the reabsorption mechanism of D-glucose in the kidney.

UR - http://www.scopus.com/inward/record.url?scp=0028234548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028234548&partnerID=8YFLogxK

M3 - Article

C2 - 8163506

AN - SCOPUS:0028234548

VL - 269

SP - 12032

EP - 12039

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 16

ER -