Molecular characteristics of Na+-coupled glucose transporters in adult and embryonic rat kidney

G. You, W. S. Lee, E. J G Barros, Y. Kanai, T. L. Huo, S. Khawaja, R. G. Wells, S. K. Nigam, M. A. Hediger

研究成果: 雜誌貢獻文章

163 引文 斯高帕斯(Scopus)

摘要

Two distinct Na+-coupled glucose transporters (SGLTs) with either a high or a low affinity for glucose were shown to provide reabsorption of filtered glucose in the kidney. We have previously reported the characteristics of the high affinity Na+/glucose cotransporter SGLT1 from rabbit, rat, and human kidney and the low affinity Na+/glucose cotransporter SGLT2 from human kidney. Because the molecular identity of SGLT2 as the kidney cortical low affinity Na+/glucose cotransporter has been recently challenged based on studies of the porcine low affinity Na+/glucose cotransporter SAAT-pSGLT2 (Mackenzie, B., Panayotova-Heiermann, M., Leo, D. D. F., Lever, J. E., and Wright, E. M. (1994) J. Biol. Chem. 269, 22488-22491), we have reevaluated the properties of SGLT2 in greater detail. We furthermore report new data on the regulation of SGLT1 and SGLT2 during kidney development. To analyze and compare SGLT1 and SGLT2 in adult and embryonic kidney, we have cloned and characterized SGLT2 from rat kidney and determined its tissue distribution based on Northern analysis and in situ hybridization. When expressed in Xenopus oocytes, rat SGLT2 stimulated transport of α-methyl-D- glucopyranoside (2 mM) in oocytes up to 4.5-fold over controls with an apparent K(m) of 3.0 mM. The transport properties (i.e. a Na+ to glucose coupling of 1:1 and lack of galactose transport) generally matched those of the kidney cortical low affinity system. We show that expression of rat SGLT2 mRNA is kidney specific and that it is strongly and exclusively expressed in proximal tubule S1 segments. Hybrid-depletion studies were performed to conclusively determine whether SGLT2 corresponds to the kidney cortical low affinity system. Injection of rat kidney superficial cortex mRNA into oocytes stimulated the uptake of α-methyl-D-glucopyranoside (2 mM) 2-3-fold. We show that hybrid depletion of this kidney RNA using an SGLT2 antisense oligonucleotide completely suppresses the uptake. These data strongly indicate that SGLT2 is the major kidney cortical low affinity glucose transporter. We therefore propose that SAAT-pSGLT2 be renamed SGLT3. Experiments addressing the expression of SGLT1 and SGLT2 mRNAs in embryonic rat kidneys reveal that the two Na+/glucose cotransporters are developmentally regulated and that there may be a different splice variant for SGLT2 in embryonic kidney compared to the adult.

原文英語
頁(從 - 到)29365-29371
頁數7
期刊Journal of Biological Chemistry
270
發行號49
DOIs
出版狀態已發佈 - 1995
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry

指紋 深入研究「Molecular characteristics of Na<sup>+</sup>-coupled glucose transporters in adult and embryonic rat kidney」主題。共同形成了獨特的指紋。

  • 引用此

    You, G., Lee, W. S., Barros, E. J. G., Kanai, Y., Huo, T. L., Khawaja, S., Wells, R. G., Nigam, S. K., & Hediger, M. A. (1995). Molecular characteristics of Na+-coupled glucose transporters in adult and embryonic rat kidney. Journal of Biological Chemistry, 270(49), 29365-29371. https://doi.org/10.1074/jbc.270.49.29365