Abstract：
BACKGROUND AND PURPOSE:The renal sodium-glucose cotransporter 2 (SGLT2) plays an important role in the reuptake of filtered glucose in the proximal tubule and therefore may be an attractive target for the treatment of diabetes mellitus. This study characterizes the pharmacological profile of TS-071 ((1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol hydrate), a novel SGLT2 inhibitor in vitro and in vivo. EXPERIMENTAL APPROACH:Inhibition of glucose uptake by TS-071 was studied in CHO-K1 cells stably expressing either human SGLT1 or SGLT2. Single oral dosing studies were performed in rats, mice and dogs to assess the abilities of TS-071 to increase urinary glucose excretion and to lower plasma glucose levels. KEY RESULTS:TS-071 inhibited SGLT2 activity in a concentration-dependent manner and was a potent and highly selective inhibitor of SGLT2. Orally administered TS-071 increased urinary glucose excretion in Zucker fatty rats and beagle dogs at doses of 0.3 and 0.03 mg·kg(-1) respectively. TS-071 improved glucose tolerance in Zucker fatty rats without stimulating insulin secretion and reduced hyperglycaemia in streptozotocin (STZ)-induced diabetic rats and db/db mice at a dose of 0.3 mg·kg(-1). CONCLUSION AND IMPLICATIONS:These data indicate that TS-071 is a potent and selective SGLT2 inhibitor that improves glucose levels in rodent models of type 1 and 2 diabetes and may be useful for the treatment for diabetes mellitus.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Yamamoto K,Uchida S,Kitano K,Fukuhara N,Okumura-Kitajima L,Gunji E,Kozakai A,Tomoike H,Kojima N,Asami J,Toyoda H,Arai M,Takahashi T,Takahashi Kdoi
10.1111/j.1476-5381.2011.01340.xsubject
Has Abstractpub_date
2011-09-01 00:00:00pages
181-91issue
1eissn
0007-1188issn
1476-5381journal_volume
164pub_type
杂志文章abstract：:1. A comparative study was carried out to assess the regional haemodynamic effects of intravenous infusion of human alpha- and beta-calcitonin gene-related peptide (CGRP; 0.006, 0.06 and 0.6 nmol h-1) in conscious, unrestrained Wistar rats. 2. With human alpha-CGRP, tachycardia was always accompanied by a fall in mean...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12668.x
更新日期：1989-12-01 00:00:00
abstract：:1. The possible roles of endothelial and smooth muscle cell hyperpolarization and nitric oxide (NO) in endothelium-dependent relaxation were examined in isolated rings of pig right coronary artery. 2. The effects of hyperpolarization were prevented with high K+ (30-125 mM), isotonic Krebs solutions. Functional antagon...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13110.x
更新日期：1994-06-01 00:00:00
abstract：:1. [Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 (Phepsi), a tridecapeptide analogue of orphanin FQ/nociceptin (OFQ/N), was introduced as a competitive antagonist of opioid receptor-like orphan receptor (ORL1) in guinea-pig ileum and mouse vas deferens preparations in vitro but was recently found to act as an agonist i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702746
更新日期：1999-09-01 00:00:00
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doi：10.1111/bph.12817
更新日期：2014-11-01 00:00:00
abstract：:Cyclo-oxygenase (COX) inhibitors potentiate opioid inhibition of GABAergic synaptic transmission in rat periaqueductal grey (PAG) (Vaughan et al., 1997). In the present study, the relative contribution of cyclo-oxygenase-1 (COX-1) and COX-2 inhibition to this phenomenon was examined by use of whole-cell patch clamp re...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701818
更新日期：1998-04-01 00:00:00
abstract：:Transient expression in COS-7 cells of the recombinant human 5-hydroxytryptamine (5-HT) h5-HT4(c) receptor isoform led to constitutive activity of the receptor. The 5-HT4 receptor antagonist 2-(cis-3,5-dimethylpiperidino)ethyl 4-amino-5-chloro-2-methoxybenzoate (ML10375) at 1 microM completely abolished the 5-HT (1 mi...
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0702163
更新日期：1998-10-01 00:00:00
abstract：:1. Bicyclic compounds with potential thymoleptic properties (Lu-compounds) have recently become available, and their effects on the membrane pumps of the central and peripheral monoamine neurones have now been tested and compared with those of the tricyclic antidepressant drugs.2. Biochemical and histochemical in vivo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb08299.x
更新日期：1969-05-01 00:00:00
abstract：:1. Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single-unit extracellular recording techniques. 2. In anaesthetized rats, local (27 pm...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702255
更新日期：1998-12-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1038/sj.bjp.0707299
更新日期：2007-08-01 00:00:00
abstract：:The antioestrogen, tamoxifen, blocks volume-regulated chloride channels and reduces transparency in bovine lenses maintained in vitro. In contrast to tamoxifen, the steroidal antioestrogen, ICI 182780, did not block volume-regulated chloride currents in three cultured cell lines and required 10 fold higher concentrati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16622.x
更新日期：1995-08-01 00:00:00
abstract：:1. The inhibitory effect of caffeine on the calcium channel current was investigated in cultured myometrial cells isolated from pregnant rats. 2. Caffeine inhibited the calcium channel current elicited from a holding potential of -70 mV in a concentration-dependent manner. The IC50 was estimated to be 35 mM. 3. The ca...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12622.x
更新日期：1989-10-01 00:00:00
abstract：:1. The role played by endogenous lipocortin 1 in the anti-migratory action exerted by dexamethasone (Dex) on monocyte recruitment in an in vivo model of acute inflammation was investigated by use of several neutralizing polyclonal antibodies raised against lipocortin 1 or a lipocortin 1-derived N-terminus peptide (pep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701029
更新日期：1997-03-01 00:00:00
abstract：:1. Antilaminin IgG decreased the dF/dt of mouse isolated atria and inhibited the mechanical effect of acetylcholine in a non-competitive fashion. 2. Inhibitors of nicotinic and muscarinic cholinoceptors impaired the negative inotropic action of antilaminin IgG in mouse isolated atria. Hemicholinium and tetrodotoxin al...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11964.x
更新日期：1989-06-01 00:00:00
abstract：:1. Rat mesenteric (approximately 250 microns) were set up in a single-channel isometric myograph designed to allow with 6 microM fura-2AM for 2 h and simultaneous recordings of neurogenic contraction (force) and intracellular calcium [Ca2+]i were obtained. In other experiments, arteries were loaded with 1 microCi ml-1...
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0701337
更新日期：1997-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown. EXPERIMENTAL APPROACH:Human dental follicle cells (hDFCs) were treated by bleom...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15281
更新日期：2020-10-17 00:00:00
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15151.x
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12618.x
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更新日期：1999-12-01 00:00:00
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更新日期：2011-07-01 00:00:00
abstract：:1 The present study comprised treatment of healthy male rats with Delta(9)-tetrahydrocannabinol (THC, 10 mg kg(-1), p.o.), and combinations of THC with benzoflavone moiety (BZF, 10 and 20 mg kg(-1), p.o.) isolated from Passiflora incarnata Linneaus, over a period of 30 days. 2 Upon 30-days chronic administrations, the...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0705015
更新日期：2003-01-01 00:00:00
abstract：:1. The effect of a single injection of the monoamine oxidase inhibitor, tranylcypromine, administered intravenously (20 mg/kg) or into the lateral cerebral ventricle (5-10 mg), on hypothalamic and rectal temperature, has been investigated.2. Intravenous tranylcypromine causes a significant rise in body temperature, wh...
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doi：10.1111/j.1476-5381.1970.tb10594.x
更新日期：1970-05-01 00:00:00
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doi：10.1038/sj.bjp.0705860
更新日期：2004-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
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更新日期：2014-06-01 00:00:00
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doi：10.1038/sj.bjp.0703589
更新日期：2000-09-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1993.tb12852.x
更新日期：1993-03-01 00:00:00
abstract：:1. The aim of the present experiments was to determine whether 5-HT1A receptors play a role in the control of the reflex activation of pulmonary vagal motoneurones. This was carried out by investigating the effects of intracisternal injections (i.c.) of the 5-HT1A receptor ligands, 8-OH-DPAT (50 micrograms kg-1), busp...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1996.tb15250.x
更新日期：1996-02-01 00:00:00
abstract：:1. Two-electrode voltage clamp was used to study the effects of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate (cyclic GMP) on voltage-dependent ion channels in salivary gland cells of the leech, Haementeria ghilianii. 2. Intracellular cyclic AMP specifically blocked delayed...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16673.x
更新日期：1995-09-01 00:00:00
