{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:37:11Z","timestamp":1778276231072,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2950,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The therapeutic effects of an orally active inhibitor of Na<jats:sup>+<\/jats:sup>\u2010glucose cotransporter (SGLT), T\u20101095 (a derivative of phlorizin; 3\u2010(benzo[<jats:italic>b<\/jats:italic>]furan\u20105\u2010yl)\u20102\u2032,6\u2032\u2010dihydroxy\u20104\u2032\u2010methylpropiophenone 2\u2032\u2010<jats:italic>O<\/jats:italic>\u2010(6\u2010<jats:italic>O<\/jats:italic>\u2010methoxycarbonyl\u2010\u03b2\u2010<jats:sc>D<\/jats:sc>\u2010glycopyranoside)) were examined in C57BL\/KsJ\u2010db\/db (db\/db) mice, a genetic animal model of obese type 2 diabetes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The higher renal SGLT activity in db\/db mice than normoglycaemic C57BL\/KsJ\u2010db\/+m (db\/+m) mice may support the rationale for using an SGLT inhibitor in the treatment regimen for type 2 diabetes. Both T\u20101095 and its metabolite, T\u20101095A, which had approximately 10 times more potency, effectively inhibited renal SGLT activity of these mice <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Single oral administration of T\u20101095 (10, 30, 100\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, p.o.) to db\/db mice caused a dose\u2010dependent reduction in blood glucose levels and a concomitant increase in glucose excretion into urine. In contrast, T\u20101095 only slightly affected blood glucose levels in db\/+m mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Chronic administration of T\u20101095 (0.1% w w<jats:sup>\u22121<\/jats:sup> pellet chow, for 12 weeks) decreased blood glucose and haemoglobin A<jats:sub>1C<\/jats:sub> levels, and improved glucose intolerance in db\/db mice. The age\u2010related decrease in plasma insulin levels was markedly inhibited and there was a 2.5 fold increase of insulin content in the pancreas of T\u20101095\u2010treated db\/db mice. Food consumption was not changed, while impaired body weight gain was ameliorated by T\u20101095 treatment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Both the development of albuminuria and the expansion of glomerular mesangial area in db\/db mice were significantly suppressed by chronic T\u20101095 treatment, indicating the prevention of the progression of diabetic nephropathy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results demonstrate that the SGLT inhibitor T\u20101095 is able to improve the metabolic abnormalities and inhibit the development of diabetic complications in db\/db mice. Thus, T\u20101095 can be used for therapy of type 2 diabetic patients.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>132<\/jats:bold>, 578\u2013586; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703829\">10.1038\/sj.bjp.0703829<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703829","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:09:20Z","timestamp":1106946560000},"page":"578-586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["Improved diabetic syndrome in C57BL\/KsJ\u2010db\/db mice by oral administration of the Na<sup>+<\/sup>\u2010glucose cotransporter inhibitor T\u20101095"],"prefix":"10.1111","volume":"132","author":[{"given":"Kenji","family":"Arakawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Oku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masao","family":"Nawano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiichiro","family":"Ueta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"543","article-title":"Development of the insulin secretory defect in genetically diabetic (db\/db) mouse","volume":"87","author":"BERGLUND O.","year":"1978","journal-title":"Acta Endocrinol."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(90)90120-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.219"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","unstructured":"THE DIABETES CONTROL AND COMPLICATIONS TRIAL (DCCT) RESEARCH GROUP. 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