Dapagliflozin binds specifically to sodium-glucose cotransporter 2 in the proximal renal tubule

Journal of the American Society of Nephrology

Volumn 28, Issue 3, 2017, Pages 802-810

  Ghezzi, Chiara ^a   Yu, Amy S ^a   Hirayama, Bruce A ^a   Kepe, Vladimir ^a   Liu, Jie ^a   Scafoglio, Claudio ^a   Powell, David R ^b   Huang, Sung Cheng ^a   Satyamurthy, Nagichettiar ^a   Barrio, Jorge R ^a   Wright, Ernest M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b LEXICON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DAPAGLIFLOZIN; FLUORODEOXYGLUCOSE F 18; PHLORIZIN; SODIUM GLUCOSE COTRANSPORTER 2; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; BENZHYDRYL DERIVATIVE; GLUCOSIDE;

ANIMAL EXPERIMENT; APICAL MEMBRANE; ARTICLE; AUTORADIOGRAPHY; BILE; BRAIN; CONTROLLED STUDY; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG PROTEIN BINDING; FEMALE; HEART; KIDNEY CORTEX; KIDNEY PROXIMAL TUBULE; LIVER; MALE; MOUSE; MUSCLE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SALIVARY GLAND; WILD TYPE; ANIMAL; C57BL MOUSE; METABOLISM; SPRAGUE DAWLEY RAT;

ANIMALS; BENZHYDRYL COMPOUNDS; FEMALE; GLUCOSIDES; KIDNEY TUBULES, PROXIMAL; MALE; MICE; MICE, INBRED C57BL; RATS; RATS, SPRAGUE-DAWLEY; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 85021851289     PISSN: 10466673     EISSN: 15333450     Source Type: Journal    
DOI: 10.1681/ASN.2016050510     Document Type: Article

References (29)

1. Vallon V: Molecular determinants of renal glucose reabsorption. Focus on "Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2." Am J Physiol Cell Physiol 300: C6-C8, 2011.
2. Gorboulev V, Schürmann A, Vallon V, Kipp H, Jaschke A, Klessen D, Friedrich A, Scherneck S, Rieg T, Cunard R, Veyhl-Wichmann M, Srinivasan A, Balen D, Breljak D, Rexhepaj R, Parker HE, Gribble FM, Reimann F, Lang F, Wiese S, Sabolic I, Sendtner M, Koepsell H: Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61: 187-196, 2012.
3. Jurczak MJ, Lee HY, Birkenfeld AL, Jornayvaz FR, Frederick DW, Pongratz RL, Zhao X, Moeckel GW, Samuel VT, Whaley JM, Shulman GI, Kibbey RG: SGLT2 deletion improves glucose homeostasis and preserves pancreatic beta-cell function. Diabetes 60: 890-898, 2011.
4. Powell DR, DaCosta CM, Gay J, Ding ZM, Smith M, Greer J, Doree D, Jeter-Jones S, Mseeh F, Rodriguez LA, Harris A, Buhring L, Platt KA, Vogel P, Brommage R, Shadoan MK, Sands AT, Zambrowicz B: Improved glycemic control in mice lacking Sglt1 and Sglt2. Am J Physiol Endocrinol Metab 304: E117-E130, 2013.
5. Phelps ME: PET: Molecular Imaging and Its Biological Applications, New York, Springer-Verlag, 2004.
6. Sala-Rabanal M, Hirayama BA, Ghezzi C, Liu J, Huang SC, Kepe V, Koepsell H, Yu A, Powell DR, Thorens B, Wright EM, Barrio JR: Revisiting the physiological roles of SGLTs and GLUTs using positron emission tomography in mice. J Physiol 594: 4425-4438, 2016.
7. Gallo LA, Wright EM, Vallon V: Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences. Diab Vasc Dis Res 12: 78-89, 2015.
8. Obermeier M, Yao M, Khanna A, Koplowitz B, Zhu M, Li W, Komoroski B, Kasichayanula S, Discenza L, Washburn W, Meng W, Ellsworth BA, Whaley JM, Humphreys WG: In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos 38: 405- 414, 2010.
9. Scafoglio C, Hirayama BA, Kepe V, Liu J, Ghezzi C, Satyamurthy N, Moatamed NA, Huang J, Koepsell H, Barrio JR, Wright EM: Functional expression of sodium-glucose transporters in cancer. Proc Natl Acad Sci U S A 112: E4111-E4119, 2015.
10. Yu AS, Hirayama BA, Timbol G, Liu J, Basarah E, Kepe V, Satyamurthy N, Huang SC, Wright EM, Barrio JR: Functional expression of SGLTs in rat brain. Am J Physiol Cell Physiol 299: C1277-C1284, 2010.
11. Abdul-Ghani MA, Norton L, Defronzo RA: Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev 32: 515-531, 2011.
12. Hummel CS, Lu C, Liu J, Ghezzi C, Hirayama BA, LooD D, Kepe V, Barrio JR, Wright EM: Structural selectivity of human SGLT inhibitors. Am J Physiol Cell Physiol 302: C373-C382, 2012.
13. Meng W, Ellsworth BA, Nirschl AA, McCann PJ, Patel M, Girotra RN, Wu G, Sher PM, Morrison EP, Biller SA, Zahler R, Deshpande PP, Pullockaran A, Hagan DL, Morgan N, Taylor JR, Obermeier MT, Humphreys WG, Khanna A, Discenza L, Robertson JG, Wang A, Han S, Wetterau JR, Janovitz EB, Flint OP, Whaley JM, Washburn WN: Discovery of dapagliflozin: A potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 51: 1145-1149, 2008.
14. Kanai Y, Lee WS, You G, Brown D, Hediger MA: The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest 93: 397-404, 1994.
15. Sabolic I, Vrhovac I, Eror DB, Gerasimova M, Rose M, Breljak D, LjubojevicM, Brzica H, Sebastiani A, Thal SC, Sauvant C, Kipp H, Vallon V, Koepsell H: Expression of Na+-D-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences. Am J Physiol Cell Physiol 302: C1174-C1188, 2012.
16. Vrhovac I, Balen Eror D, Klessen D, Burger C, Breljak D, Kraus O, Radovic N, Jadrijevic S, Aleksic I, Walles T, Sauvant C, Sabolic I, Koepsell H: Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart. Pflugers Arch 467: 1881-1898, 2015.
17. Kasichayanula S, Chang M, Hasegawa M, Liu X, Yamahira N, LaCreta FP, Imai Y, Boulton DW: Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-Transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus. Diabetes Obes Metab 13: 357-365, 2011.
18. Silverman M: The in vivo localization of high-Affinity phlorizin receptors to the brush border surface of the proximal tubule in dog kidney. Biochim Biophys Acta 339: 92-102, 1974.
19. Ghezzi C, Hirayama BA, Gorraitz E, Loo DD, Liang Y, Wright EM: SGLT2 inhibitors act from the extracellular surface of the cell membrane. Physiol Rep 2: E12058, 2014.
20. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-Transporter type 2. Clin Pharmacokinet 53: 17-27, 2014.
21. Scheen AJ: Evaluating SGLT2 inhibitors for type 2 diabetes: Pharmacokinetic and toxicological considerations. Expert Opin Drug Metab Toxicol 10: 647-663, 2014.
22. Ghezzi C, Wright EM: Regulation of the human Na+-dependent glucose cotransporter hSGLT2. AmJ Physiol Cell Physiol 303:C348-C354, 2012.
23. Wright EM, Barrio JR, Hirayama BA, Kepe V: Tracers for monitoring the activity of Sodium/Glucose cotransporters in health and disease. United States Patent US 8, 845, 99 B2, 2014.
24. Wright EM, Turk E, Martín MG: Molecular basis for glucose-galactose malabsorption. Cell Biochem Biophys 36: 115-121, 2002.
25. Suckow C, Kuntner C, Chow P, Silverman R, Chatziioannou A, Stout D: Multimodality rodent imaging chambers for use under barrier conditions with gas anesthesia. Mol Imaging Biol 11: 100-106, 2009.
26. Loening AM, Gambhir SS: AMIDE: A free software tool for multimodality medical image analysis. Mol Imaging 2: 131-137, 2003.
27. Berger F, Lee YP, Loening AM, Chatziioannou A, Freedland SJ, Leahy R, Lieberman JR, Belldegrun AS, Sawyers CL, Gambhir SS: Whole-body skeletal imaging in mice utilizing microPET: Optimization of reproducibility and applications in animal models of bone disease. Eur J Nucl Med Mol Imaging 29: 1225-1236, 2002.
28. Jespersen B, Knupp L, Northcott CA: Femoral arterial and venous catheterization for blood sampling, drug administration and conscious blood pressure and heart rate measurements. J Vis Exp 59: 3496, 2012.
29. Chasis H, Jolliffe N, Smith HW: The action of phlorizin on the excretion of glucose, xylose, sucrose, creatinine and urea by men. J Clin Invest 12: 1083-1090, 1933.