Selective SGLT2 inhibition by tofogliflozin reduces renal glucose reabsorption under hyperglycemic but not under hypo- or euglycemic conditions in rats

American Journal of Physiology - Endocrinology and Metabolism

Volumn 304, Issue 4, 2013, Pages

  Nagata, Takumi ^a   Fukazawa, Masanori ^a   Honda, Kiyofumi ^a   Yata, Tatsuo ^b   Kawai, Mio ^b   Yamane, Mizuki ^a   Murao, Naoaki ^a   Yamaguchi, Koji ^a   Kato, Motohiro ^a   Mitsui, Tetsuya ^a   Suzuki, Yoshiyuki ^a   Ikeda, Sachiya ^a   Kawabe, Yoshiki ^a  

^a Research Division   (Japan)

^b Chugai Research Institute for Medical Science   (Japan)

Author keywords

Sodium glucose cotransporter; Sodium glucose transporter inhibitor

Indexed keywords

GLUCOSE; PHLORIZIN; TOFOGLIFLOZIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; GLUCONEOGENESIS; GLUCOSE ABSORPTION; GLUCOSE BLOOD LEVEL; GLUCOSE INFUSION; GLUCOSE URINE LEVEL; GLUCOSURIA; GLYCEMIC CONTROL; HYPERGLYCEMIA; HYPOGLYCEMIA; IN VIVO STUDY; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; RENAL GLUCOSE REABSORPTION; WISTAR RAT;

ABSORPTION; ANIMALS; BENZHYDRYL COMPOUNDS; BLOOD GLUCOSE; CREATININE; DOSE-RESPONSE RELATIONSHIP, DRUG; GLUCONEOGENESIS; GLUCOSIDES; GLYCOSURIA; HYPERGLYCEMIA; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; KIDNEY; MALE; PHLORHIZIN; RATS; RATS, WISTAR; SODIUM CHANNEL BLOCKERS; SODIUM-GLUCOSE TRANSPORTER 1; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 84874070590     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00545.2012     Document Type: Article

References (26)

1. Aljure O, Diez-Sampedro A. Functional characterization of mouse sodium/ glucose transporter type 3b. Am J Physiol Cell Physiol 299: C58-C65, 2010.
2. Bergeron R, Previs SF, Cline GW, Perret P, Russell RR, 3rd Young LH, Shulman GI. Effect of 5-aminoimidazole-4-carboxamide-1-beta-Dribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50: 1076-1082, 2001.
3. Chao EC, Henry RR. SGLT2 inhibition: a novel strategy for diabetes treatment. Nat Rev Drug Discov 9: 551-559, 2010.
4. Chasis H, Jolliffe N, Smith HW. The action of phlorizin on the excretion of glucose, xylose, sucrose, creatinine and urea by man. J Clin Invest 12: 1083-1090, 1933.
5. Chen J, Williams S, Ho S, Loraine H, Hagan D, Whaley JM, Feder JN. Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Ther 1: 57-92, 2010.
6. Ferrannini E, Solini A. SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. Nat Rev Endocrinol 8: 495-502, 2012.
7. Furler SM, Zelenka GS, Kraegen EW. Development and testing of a simple algorithm for a glucose clamp. Med Biol Eng Comput 24: 365-370, 1986.
8. Han S, Hagan DL, Taylor JR, Xin L, Meng W, Biller SA, Wetterau JR, Washburn WN, Whaley JM. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 57: 1723-1729, 2008.
9. +/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol 300: C14-C21, 2011.
10. Kadowaki T, Ikeda S, Takano Y, Cynshi O, Christ AD, Boerlin V, Beyer U, Beck A. Tofogliflozin, a novel and selective SGLT2 inhibitor improves glycemic control and lowers body weight in patients with type 2 diabetes mellitus inadequately controlled on stable metformin or diet and exercise alone (Abstract). Diabetes 61, Suppl 1: A22, 2012.
11. 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.
12. Katsuno K, Fujimori Y, Takemura Y, Hiratochi M, Itoh F, Komatsu Y, Fujikura H, Isaji M. Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther 320: 323-330, 2007.
13. Komoroski B, Vachharajani N, Boulton D, Kornhauser D, Geraldes M, Li L, Pfister M. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther 85: 520-526, 2009.
14. Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther 85: 513-519, 2009.
15. Kothinti RK, Blodgett AB, North PE, Roman RJ, Tabatabai NM. A novel SGLT is expressed in the human kidney. Eur J Pharmacol 690: 77-83, 2012
16. Liu JJ, Lee T, Defronzo RA. Why do SGLT2 inhibitors inhibit only 30-50% of renal glucose reabsorption in humans? Diabetes 61: 2199-2204, 2012.
17. Ohtake Y, Sato T, Kobayashi T, Nishimoto M, Taka N, Takano K, Yamamoto K, Ohmori M, Yamaguchi M, Takami K, Yeu SY, Ahn KH, Matsuoka H, Morikawa K, Suzuki M, Hagita H, Ozawa K, Yamaguchi K, Kato M, Ikeda S. Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 55: 7828-7840, 2012.
18. Rogatsky E, Jayatillake H, Goswami G, Tomuta V, Stein D. Sensitive LC MS quantitative analysis of carbohydrates by Cs+ attachment. J Am Soc Mass Spectrom 16: 1805-1811, 2005.
19. Rossetti L, Smith D, Shulman GI, Papachristou D, DeFronzo RA. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 79: 1510-1515, 1987.
20. Sha S, Devineni D, Ghosh A, Polidori D, Chien S, Wexler D, Shalayda K, Demarest K, Rothenberg P. Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects. Diabetes Obes Metab 13: 669-672, 2011.
21. Suzuki M, Honda K, Fukazawa M, Ozawa K, Hagita H, Kawai T, Takeda M, Yata T, Kawai M, Fukuzawa T, Kobayashi T, Sato T, Kawabe Y, Ikeda S. Tofogliflozin, a potent and highly specific sodium/ glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice. J Pharmacol Exp Ther 341: 692-701, 2012.
22. Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Qun L, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. Pharmacological profile of ipragliflozin (ASP1941), a novel selective SGLT2 inhibitor, in vitro and in vivo. Naunyn Schmiedebergs Arch Pharmacol 385: 423-436, 2012.
23. Vallon V. The proximal tubule in the pathophysiology of the diabetic kidney. Am J Physiol Regul Integr Comp Physiol 300: R1009-R1022, 2011.
24. Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson SC, Koepsell H, Rieg T. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol 22: 104-112, 2011.
25. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 91: 733-794, 2011.
26. Yamaguchi K, Kato M, Suzuki M, Asanuma K, Aso Y, Ikeda S, Ishigai M. Pharmacokinetic and pharmacodynamic modeling of the effect of an sodium-glucose cotransporter inhibitor, phlorizin, on renal glucose transport in rats. Drug Metab Dispos 39: 1801-1807, 2011.