{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:33Z","timestamp":1791978573820,"version":"4.4.0"},"reference-count":40,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2008,10]]},"DOI":"10.1124\/jpet.108.140210","type":"journal-article","created":{"date-parts":[[2008,6,26]],"date-time":"2008-06-26T21:23:52Z","timestamp":1214515432000},"page":"268-276","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":186,"title":["Remogliflozin Etabonate, in a Novel Category of Selective Low-Affinity Sodium Glucose Cotransporter (SGLT2) Inhibitors, Exhibits Antidiabetic Efficacy in Rodent Models"],"prefix":"10.1016","volume":"327","author":[{"given":"Yoshikazu","family":"Fujimori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Katsuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikumi","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Ishikawa-Takemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Fujikura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Isaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.108.140210_bib1","doi-asserted-by":"crossref","unstructured":"Adachi T, Yasuda K, Okamoto Y, Shihara N, Oku A, Ueta K, Kitamura K, Saito A, Iwakura I, Yamada Y, et al. (2000) T-1095, a renal Na+-glucose transporter inhibitor, improves hyperglycemia in streptozotocin-induced diabetic rats. Metabolism 49: 990-995.","DOI":"10.1053\/meta.2000.7729"},{"key":"10.1124\/jpet.108.140210_bib2","doi-asserted-by":"crossref","unstructured":"Arakawa K, Ishihara T, Oku A, Nawano M, Ueta K, Kitamura K, Matsumoto M, and Saito A (2001) Improved diabetic syndrome in C57BL\/KsJ-db\/db mice by oral administration of the Na(+)-glucose cotransporter inhibitor T-1095. Br J Pharmacol 132: 578-586.","DOI":"10.1038\/sj.bjp.0703829"},{"key":"10.1124\/jpet.108.140210_bib3","doi-asserted-by":"crossref","unstructured":"Ashiya M and Smith RET (2007) Non-insulin therapies for type 2 diabetes. Nat Rev Drug Discov 6: 777-778.","DOI":"10.1038\/nrd2420"},{"key":"10.1124\/jpet.108.140210_bib4","doi-asserted-by":"crossref","unstructured":"Calado J, Soto K, Clemente C, Correia P, and Rueff J (2004) Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria. Hum Genet 114: 314-316.","DOI":"10.1007\/s00439-003-1054-x"},{"key":"10.1124\/jpet.108.140210_bib5","unstructured":"Dwarakanathan A (2006) Diabetes update. J Insur Med 38: 20-30."},{"key":"10.1124\/jpet.108.140210_bib6","doi-asserted-by":"crossref","unstructured":"Ehrenkranz JR, Lewis NG, Kahn CR, and Roth J (2005) Phlorizin: a review. Diabetes Metab Res Rev 21: 31-38.","DOI":"10.1002\/dmrr.532"},{"key":"10.1124\/jpet.108.140210_bib7","doi-asserted-by":"crossref","unstructured":"Fujimoto Y, Torres TP, Donahue EP, and Shiota M (2006) Glucose toxicity is responsible for the development of impaired regulation of endogenous glucose production and hepatic glucokinase in Zucker diabetic fatty rats. Diabetes 55: 2479-2490.","DOI":"10.2337\/db05-1511"},{"key":"10.1124\/jpet.108.140210_bib8","doi-asserted-by":"crossref","unstructured":"Garber AJ (2004) The metabolic syndrome. Med Clin North Am 88: 837-846.","DOI":"10.1016\/j.mcna.2004.04.001"},{"key":"10.1124\/jpet.108.140210_bib9","doi-asserted-by":"crossref","unstructured":"Harmon JS, Gleason CE, Tanaka Y, Poitout V, and Robertson RP (2001) Antecedent hyperglycemia, not hyperlipidemia, is associated with increased islet triacylglycerol content and decreased insulin gene mRNA level in Zucker diabetic fatty rats. Diabetes 50: 2481-2486.","DOI":"10.2337\/diabetes.50.11.2481"},{"key":"10.1124\/jpet.108.140210_bib10","doi-asserted-by":"crossref","unstructured":"Hughes SJ, Suzuki K, and Goto Y (1994) The role of islet secretory function in the development of diabetes in the GK Wistar rat. Diabetologia 37: 863-870.","DOI":"10.1007\/s001250050189"},{"key":"10.1124\/jpet.108.140210_bib11","unstructured":"Isaji M (2007) Sodium-glucose cotransporter inhibitors for diabetes. Curr Opin Investig Drugs 8: 285-292."},{"key":"10.1124\/jpet.108.140210_bib12","doi-asserted-by":"crossref","unstructured":"Kanai Y, Lee WS, You G, Brown D, and Hediger MA (1994) 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.","DOI":"10.1172\/JCI116972"},{"key":"10.1124\/jpet.108.140210_bib13","doi-asserted-by":"crossref","unstructured":"Katsuno K, Fujimori Y, Takemura Y, Hiratochi M, Itoh F, Komatsu Y, Fujikura H, and Isaji M (2007) 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.","DOI":"10.1124\/jpet.106.110296"},{"key":"10.1124\/jpet.108.140210_bib14","doi-asserted-by":"crossref","unstructured":"Kees KL, Fitzgerald JJ Jr, Steiner KE, Mattes JF, Mihan B, Tosi T, Mondoro D, and McCaleb ML (1996) New potent antihyperglycemic agents in db\/db mice: synthesis and structure-activity relationship studies of (4-substituted benzyl) (trifluoromethyl)pyrazoles and -pyrazolones. J Med Chem 39: 3920-3928.","DOI":"10.1021\/jm960444z"},{"key":"10.1124\/jpet.108.140210_bib15","doi-asserted-by":"crossref","unstructured":"Leahy JL, Bonner-Weir S, and Weir GC (1992) Beta-cell dysfunction induced by chronic hyperglycemia. Current ideas on mechanism of impaired glucose-induced insulin secretion. Diabetes Care 15: 442-455.","DOI":"10.2337\/diacare.15.3.442"},{"key":"10.1124\/jpet.108.140210_bib16","doi-asserted-by":"crossref","unstructured":"Lenhard JM, Lancaster ME, Paulik MA, Weiel JE, Binz JG, Sundseth SS, Gaskill BA, Lightfoot RM, and Brown HR (1999) The RXR agonist LG100268 causes hepatomegaly, improves glycaemic control and decreases cardiovascular risk and cachexia in diabetic mice suffering from pancreatic beta-cell dysfunction. Diabetologia 42: 545-554.","DOI":"10.1007\/s001250051193"},{"key":"10.1124\/jpet.108.140210_bib17","doi-asserted-by":"crossref","unstructured":"Link JT and Sorensen BK (2000) A method for preparing C-glycosides related to phlorizin. Tetrahedron Lett 41: 9213-9217.","DOI":"10.1016\/S0040-4039(00)01709-3"},{"key":"10.1124\/jpet.108.140210_bib18","doi-asserted-by":"crossref","unstructured":"Mart\u00edn MG, Turk E, Lostao MP, Kerner C, and Wright EM (1996) Defects in Na+\/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. Nat Genet 12: 216-220.","DOI":"10.1038\/ng0296-216"},{"key":"10.1124\/jpet.108.140210_bib19","doi-asserted-by":"crossref","unstructured":"Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, and Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419.","DOI":"10.1007\/BF00280883"},{"key":"10.1124\/jpet.108.140210_bib20","doi-asserted-by":"crossref","unstructured":"Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, and Zinman B (2006) Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 49: 1711-1721.","DOI":"10.1007\/s00125-006-0316-2"},{"key":"10.1124\/jpet.108.140210_bib21","doi-asserted-by":"crossref","unstructured":"Nawano M, Oku A, Ueta K, Umebayashi I, Ishirahara T, Arakawa K, Saito A, Anai M, Kikuchi M, and Asano T (2000) Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF rats. Am J Physiol Endocrinol Metab 278: E535-E543.","DOI":"10.1152\/ajpendo.2000.278.3.E535"},{"key":"10.1124\/jpet.108.140210_bib22","doi-asserted-by":"crossref","unstructured":"Nunoi K, Yasuda K, Adachi T, Okamoto Y, Shihara N, Uno M, Tamon A, Suzuki N, Oku A, and Tsuda K (2002) Beneficial effect of T-1095, a selective inhibitor of renal Na+-glucose cotransporters, on metabolic index and insulin secretion in spontaneously diabetic GK rats. Clin Exp Pharmacol Physiol 29: 386-390.","DOI":"10.1046\/j.1440-1681.2002.03671.x"},{"key":"10.1124\/jpet.108.140210_bib23","doi-asserted-by":"crossref","unstructured":"Ohsumi K, Matsueda H, Hatanaka T, Hirama R, Umemura T, Oonuki A, Ishida N, Kageyama Y, Maezono K, and Kondo N (2003) Pyrazole-O-glucosides as novel Na(+)-glucose cotransporter (SGLT) inhibitors. Bioorg Med Chem Lett 13: 2269-2272.","DOI":"10.1016\/S0960-894X(03)00466-9"},{"key":"10.1124\/jpet.108.140210_bib24","doi-asserted-by":"crossref","unstructured":"Oku A, Ueta K, Arakawa K, Ishihara T, Nawano M, Kuronuma Y, Matsumoto M, Saito A, Tsujihara K, Anai M, et al. (1999) T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes 48: 1794-1800.","DOI":"10.2337\/diabetes.48.9.1794"},{"key":"10.1124\/jpet.108.140210_bib25","doi-asserted-by":"crossref","unstructured":"Oku A, Ueta K, Nawano M, Arakawa K, Kano-Ishihara T, Matsumoto M, Saito A, Tsujihara K, Anai M, and Asano T (2000) Antidiabetic effect of T-1095, an inhibitor of Na(+)-glucose cotransporter, in neonatally streptozotocin-treated rats. Eur J Pharmacol 391: 183-192.","DOI":"10.1016\/S0014-2999(00)00016-9"},{"key":"10.1124\/jpet.108.140210_bib26","doi-asserted-by":"crossref","unstructured":"Pajor AM and Wright EM (1992) Cloning and functional expression of a mammalian Na+\/nucleoside cotransporter. A member of the SGLT family. J Biol Chem 267: 3557-3560.","DOI":"10.1016\/S0021-9258(19)50557-9"},{"key":"10.1124\/jpet.108.140210_bib27","doi-asserted-by":"crossref","unstructured":"Portha B, Serradas P, Bailb\u00e9 D, Suzuki K, Goto Y, and Giroix MH (1991) Beta-cell insensitivity to glucose in the GK rat, a spontaneous nonobese model for type II diabetes. Diabetes 40: 486-491.","DOI":"10.2337\/diab.40.4.486"},{"key":"10.1124\/jpet.108.140210_bib28","doi-asserted-by":"crossref","unstructured":"Rossetti L, Smith D, Shulman GI, Papachristou D, and DeFronzo RA (1987) Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 79: 1510-1515.","DOI":"10.1172\/JCI112981"},{"key":"10.1124\/jpet.108.140210_bib29","doi-asserted-by":"crossref","unstructured":"Rossetti L, Giaccari A, and DeFronzo RA (1990) Glucose toxicity. Diabetes Care 13: 610-630.","DOI":"10.2337\/diacare.13.6.610"},{"key":"10.1124\/jpet.108.140210_bib30","doi-asserted-by":"crossref","unstructured":"Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JH, Kemper M, et al. (2003) Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol 14: 2873-2882.","DOI":"10.1097\/01.ASN.0000092790.89332.D2"},{"key":"10.1124\/jpet.108.140210_bib31","doi-asserted-by":"crossref","unstructured":"Starke A, Grundy S, McGarry JD, and Unger RH (1985) Correction of hyperglycemia with phloridzin restores the glucagon response to glucose in insulin-deficient dogs: implications for human diabetes. Proc Natl Acad Sci U S A 82: 1544-1546.","DOI":"10.1073\/pnas.82.5.1544"},{"key":"10.1124\/jpet.108.140210_bib32","doi-asserted-by":"crossref","unstructured":"Storlien LH, James DE, Burleigh KM, Chisholm DJ, and Kraegen EW (1986) Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. Am J Physiol Endocrinol Metab 251: E576-E583.","DOI":"10.1152\/ajpendo.1986.251.5.E576"},{"key":"10.1124\/jpet.108.140210_bib33","doi-asserted-by":"crossref","unstructured":"Turk E, Zabel B, Mundlos S, Dyer J, and Wright EM. (1991) Glucose\/galactose malabsorption caused by a defect in the Na+\/glucose cotransporter. Nature 350: 354-356.","DOI":"10.1038\/350354a0"},{"key":"10.1124\/jpet.108.140210_bib34","doi-asserted-by":"crossref","unstructured":"Ueta K, Ishihara T, Matsumoto Y, Oku A, Nawano M, Fujita T, Saito A, and Arakawa K (2005) Long-term treatment with the Na+-glucose cotransporter inhibitor T-1095 causes sustained improvement in hyperglycemia and prevents diabetic neuropathy in Goto-Kakizaki Rats. Life Sci 76: 2655-2668.","DOI":"10.1016\/j.lfs.2004.09.038"},{"key":"10.1124\/jpet.108.140210_bib35","doi-asserted-by":"crossref","unstructured":"van den Heuvel LP, Assink K, Willemsen M, and Monnens L (2002) Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose co-transporter (SGLT2). Hum Genet 111: 544-547.","DOI":"10.1007\/s00439-002-0820-5"},{"key":"10.1124\/jpet.108.140210_bib36","doi-asserted-by":"crossref","unstructured":"Walker CG, Zariwala MG, Holness MJ, and Sugden MC (2007) Diet, obesity and diabetes: a current update. Clin Sci (Lond) 112: 93-111.","DOI":"10.1042\/CS20060150"},{"key":"10.1124\/jpet.108.140210_bib37","doi-asserted-by":"crossref","unstructured":"Wells RG, Pajor AM, Kanai Y, Turk E, Wright EM, and Hediger MA (1992) Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. Am J Physiol Renal Physiol 263: F459-F465.","DOI":"10.1152\/ajprenal.1992.263.3.F459"},{"key":"10.1124\/jpet.108.140210_bib38","doi-asserted-by":"crossref","unstructured":"Wright EM (2001) Renal Na(+)-glucose cotransporters. Am J Physiol Renal Physiol 280: F10-F18.","DOI":"10.1152\/ajprenal.2001.280.1.F10"},{"key":"10.1124\/jpet.108.140210_bib39","doi-asserted-by":"crossref","unstructured":"Zhang X, Urbanski M, Patel M, Zeck RE, Cox GG, Bian H, Conway BR, Pat Beavers M, Rybczynski PJ, and Demarest KT (2005) Heteroaryl-O-glucosides as novel sodium glucose co-transporter 2 inhibitors. Part 1. Bioorg Med Chem Lett 15: 5202-5206.","DOI":"10.1016\/j.bmcl.2005.08.067"},{"key":"10.1124\/jpet.108.140210_bib40","doi-asserted-by":"crossref","unstructured":"Zhang X, Urbanski M, Patel M, Cox GG, Zeck RE, Bian H, Conway BR, Beavers MP, Rybczynski PJ, and Demarest KT (2006) Indole-glucosides as novel sodium glucose co-transporter 2 (SGLT2) inhibitors. Part 2. Bioorg Med Chem Lett 16: 1696-1701.","DOI":"10.1016\/j.bmcl.2005.12.006"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524346361?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524346361?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.108.140210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T17:45:44Z","timestamp":1739987144000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524346361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,10]]}},"alternative-id":["S0022356524346361"],"URL":"https:\/\/doi.org\/10.1124\/jpet.108.140210","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2008,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Remogliflozin Etabonate, in a Novel Category of Selective Low-Affinity Sodium Glucose Cotransporter (SGLT2) Inhibitors, Exhibits Antidiabetic Efficacy in Rodent Models","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.108.140210","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2008 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}