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Diabetes Therapy
Published in: Diabetes Therapy 2/2010

Open Access 01-12-2010 | Original Research

Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members

Authors: Jian Chen, Sandy Williams, Samantha Ho, Howard Loraine, Deborah Hagan, Jean M. Whaley, John N. Feder

Published in: Diabetes Therapy | Issue 2/2010

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Abstract

SGLT2 (for “Sodium GLucose coTransporter” protein 2) is the major protein responsible for glucose reabsorption in the kidney and its inhibition has been the focus of drug discovery efforts to treat type 2 diabetes. In order to better clarify the human tissue distribution of expression of SGLT2 and related members of this cotransporter class, we performed TaqMan™ (Applied Biosystems, Foster City, CA, USA) quantitative polymerase chain reaction (PCR) analysis of SGLT2 and other sodium/glucose transporter genes on RNAs from 72 normal tissues from three different individuals. We consistently observe that SGLT2 is highly kidney specific while SGLT5 is highly kidney abundant; SGLT1, sodium-dependent amino acid transporter (SAAT1), and SGLT4 are highly abundant in small intestine and skeletal muscle; SGLT6 is expressed in the central nervous system; and sodium myoinositol cotransporter is ubiquitously expressed across all human tissues.
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Literature
1.
2.
3.
Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications. Kidney Int. 2009;75:1272–1277.PubMedCrossRef
4.
Bailey CJ, Gross JL, Pieters A, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375:2223–2233.PubMedCrossRef
5.
6.
Hediger MA, Coady MJ, Ikeda TS, Wright EM. Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. Nature. 1987;330:379–381.PubMedCrossRef
7.
Lee WS, Kanai Y, Wells RG, Hediger MA. The high affinity Na+/glucose cotransporter. Re-evaluation of function and distribution of expression. J Biol Chem. 1994;269:12032–12039.PubMed
8.
Martín MG, Turk E, Lostao MP, et al. Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. Nat Genet. 1996;12:216–220.PubMedCrossRef
9.
Wells RG, Pajor AM, Kanai Y, et al. Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. Am J Physiol. 1992;263:F459–465.PubMed
10.
Kanai Y, Lee WS, You G, et al. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest. 1994;93:397–404.PubMedCrossRef
11.
Kong CT, Yet SF, Lever JE. Cloning and expression of a mammalian Na+/amino acid cotransporter with sequence similarity to Na+/glucose cotransporters. J Biol Chem. 1993;268:1509–1512.PubMed
12.
Mackenzie B, Panayotova-Heiermann M, Loo DD, et al. SAAT1 is a low affinity Na+/glucose cotransporter and not an amino acid transporter. A reinterpretation. J Biol Chem. 1994;269:22488–22491.PubMed
13.
Diez-Sampedro A, Hirayama BA, Osswald C, et al. A glucose sensor hiding in a family of transporters. Proc Natl Acad Sci USA. 2003;100:11753–11758.PubMedCrossRef
14.
Berry GT, Mallee JJ, Kwon HM, et al. The human osmoregulatory Na+/myo-inositol cotransporter gene (SLC5A3): molecular cloning and localization to chromosome 21. Genomics. 1995;25:507–513.PubMedCrossRef
15.
Hale CC, Rubin LJ. Ion specificity and stoichiometry of the cardiac inositol transporter. J Mol Cell Cardiol. 1995;27:1123–1130.PubMedCrossRef
16.
Tazawa S, Yamato T, Fujikura H, et al. SLC5A9/SGLT4, a new Na+-dependent glucose transporter, is an essential transporter for mannose, 1,5-anhydro-D-glucitol, and fructose. Life Sci. 2005;76:1039–1050.PubMedCrossRef
17.
Strausberg RL, Feingold EA, Grouse LH, et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci USA. 2002;99:16899–16903.PubMedCrossRef
18.
Roll P, Massacrier A, Pereira S, et al. New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families. Gene. 2002;285:141–148.PubMedCrossRef
19.
Coady MJ, Wallendorff B, Gagnon DG, Lapointe J. Identification of a novel Na+/myo-inositol cotransporter. J Biol Chem. 2002;277:35219–35224.PubMedCrossRef
20.
You G, Lee WS, Barros EJ, et al. Molecular characteristics of Na(+)-coupled glucose transporters in adult and embryonic rat kidney. J Biol Chem. 1995;270:29365–29371.PubMedCrossRef
21.
Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. 2007;261:32–43.PubMedCrossRef
22.
Zhou L, Cryan EV, D’Andrea MR, et al. Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1). J Cell Biochem. 2003;90:339–346.PubMedCrossRef
23.
Rubera I, Poujeol C, Bertin G, et al. Specific Cre/Lox recombination in the mouse proximal tubule. J Am Soc Nephrol. 2004;15:2050–2056.PubMedCrossRef
24.
Silverman M, Speight P, Ho L. Identification of two unique polypeptides from dog kidney outer cortex and outer medulla that exhibit different Na+/D-glucose cotransport functional properties. Biochim Biophys Acta. 1993;1153:43–52.PubMedCrossRef
25.
Canani RB, De Marco G, Passariello A, et al. Inhibitory effect of HIV-1 Tat protein on the sodium-D-glucose symporter of human intestinal epithelial cells. AIDS. 2006;20:5–10.PubMedCrossRef
26.
Lahjouji K, Aouameur R, Bissonnette P, et al. Expression and functionality of the Na+/myo-inositol cotransporter SMIT2 in rabbit kidney. Biochim Biophys Acta. 2007;1768:1154–1159.PubMedCrossRef
27.
Balen D, Ljubojevic M, Breljak D, et al. Revised immunolocalization of the Na+-D-glucose cotransporter SGLT1 in rat organs with an improved antibody. Am J Physiol Cell Physiol. 2008;295:C475–489.PubMedCrossRef
28.
Vallon V, Platt KA, Cunard R, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2010. In press.
29.
Yu AS, Hirayama BA, Timbol G, et al. Functional expression of SGLTs in rat brain. Am J Physiol Cell Physiol. 2010. In press.
30.
Barber RD, Harmer DW, Coleman RA, Clark BJ. GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genomics. 2005;21:389–395.PubMedCrossRef
31.
32.
Poppe R, Karbach U, Gambaryan S, et al. Expression of the Na+-D-glucose cotransporter SGLT1 in neurons. J Neurochem. 1997;69:84–94.PubMedCrossRef
33.
Elfeber K, Köhler A, Lutzenburg M, et al. Localization of the Na+-D-glucose cotransporter SGLT1 in the blood-brain barrier. Histochem Cell Biol. 2004;121:201–207.PubMedCrossRef
34.
Tong H, Leasure CD, Hou X, Yuen G, Briggs W, He Z. Role of root UV-B sensing in Arabidopsis early seedling development. Proc Natl Acad Sci USA. 2008;105:21039–21044.PubMedCrossRef
35.
Leasure CD, Tong H, Yuen G, Hou X, Sun X, He Z. ROOT UV-B SENSITIVE2 acts with ROOT UV-B SENSITIVE1 in a root ultraviolet B-sensing pathway. Plant Physiol. 2009;150:1902–1915.PubMedCrossRef
36.
Wu C, Orozco C, Boyer J, et al. BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biology. 2009;10:R130.PubMedCrossRef
37.
Tsai LJ, Hsiao SH, Tsai LM, et al. The sodium-dependent glucose cotransporter SLC5A11 as an autoimmune modifier gene in SLE. Tissue Antigens. 2008;71:114–126.PubMedCrossRef
38.
Han S, Hagan DL, Taylor JR, et al. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes. 2008;57:1723–1729.PubMedCrossRef
39.
Grempler R, Thomas L, Eckhardt M, et al. In vitro properties and in vivo effect on urinary glucose excretion of BI 10773, a novel selective SGLT2 inhibitor. Diabetes. 2009;58(suppl. 1);A139.
40.
Nomura S, Sakamaki S, Hongu M, et al. Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus. J Med Chem. 2010;53:6355–6360.PubMedCrossRef
41.
Kurosaki E, Tahara A, Yokono M, et al. In vitro and in vivo pharmacological properties of ASP1941: a novel, potent and selective SGLT2 inhibitor. Diabetes. 2010;59(suppl. 1):A156.
42.
Freiman J, Ruff DA, Frazier K, et al. LX4211, a dual SGLT2/SGLT1 inhibitor, shows rapid and significant improvement in glycemic control over 28 days in patients with type 2 diabetes (T2D). American Diabetes Association 2010; poster #17-LB. Available at: www.​lexicon-genetics.​com. Last accessed July 13, 2010.
Metadata
Title
Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members
Authors
Jian Chen
Sandy Williams
Samantha Ho
Howard Loraine
Deborah Hagan
Jean M. Whaley
John N. Feder
Publication date
01-12-2010
Publisher
Springer Healthcare Communications
Published in
Diabetes Therapy / Issue 2/2010
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-010-0006-4

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