{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:44:06Z","timestamp":1790016246629,"version":"4.0.1"},"reference-count":57,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20\u200amg\/kg per day), pioglitazone (2.5\u200amg\/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20\u200amg\/kg per day to pioglitazone treatment does not enhance the prevention\/delay of diabetes onset.<\/jats:p>","DOI":"10.1530\/joe-13-0601","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T02:02:09Z","timestamp":1394762529000},"page":"133-144","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":12,"title":["Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats"],"prefix":"10.1530","volume":"221","author":[{"given":"Bethany P","family":"Cummings","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Bettaieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimber","family":"Stanhope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawaz G","family":"Haj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Havel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"issue":"3-4","key":"1_34829894","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.lfs.2009.04.024","volume":"85","author":"Asakawa","year":"2009","journal-title":"Life sciences","ISSN":"https:\/\/id.crossref.org\/issn\/0024-3205","issn-type":"print"},{"issue":"6","key":"2_28646842","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-5085","issn-type":"print"},{"key":"3_47567473","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1111\/j.1463-1326.2011.01463.x","volume":"13","year":"2011","journal-title":"DIABETES OBESITY METABOLISM"},{"issue":"6","key":"4_18180212","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1210\/en.2004-0015","volume":"145","year":"2004","journal-title":"Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0013-7227","issn-type":"print"},{"issue":"6","key":"5_32005734","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/j.cell.2008.07.048","volume":"134","author":"Cao","year":"2008","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"issue":"6-7","key":"6_36363598","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.bbabio.2009.12.017","volume":"1797","author":"Cardoso","year":"2010","journal-title":"Biochimica et Biophysica Acta. Protein Structure and Molecular Enzymology","ISSN":"https:\/\/id.crossref.org\/issn\/0006-3002","issn-type":"print"},{"issue":"6","key":"7_32054081","doi-asserted-by":"publisher","first-page":"R1782","DOI":"10.1152\/ajpregu.90635.2008","volume":"295","year":"2008","journal-title":"American Journal of Physiology - Regulatory, Integrative and Comparative Physiology","ISSN":"https:\/\/id.crossref.org\/issn\/0363-6119","issn-type":"print"},{"issue":"10","key":"8_37564145","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.2337\/db09-1564","volume":"59","year":"2010","journal-title":"Diabetes","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1797","issn-type":"print"},{"key":"9_46077780","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0953-6205(00)00106-0","volume":"11","year":"2000","journal-title":"EUROPEAN JOURNAL OF INTERNAL MEDICINE"},{"issue":"9785","key":"10_40224218","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0140-6736(11)60679-X","volume":"378","author":"Danaei","year":"2011","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"issue":"8","key":"11_40142771","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1210\/jc.2011-0246","volume":"96","year":"2011","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"12","key":"12_31964148","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.2337\/dc08-1035","volume":"31","year":"2008","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"issue":"12","key":"13_39550930","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1056\/NEJMoa1010949","volume":"364","author":"DeFronzo","year":"2011","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"5","key":"14_42079744","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1210\/jc.2011-2243","volume":"97","year":"2012","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"9548","key":"15_22980680","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1016\/S0140-6736(06)69705-5","volume":"368","author":"Drucker","year":"2006","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"key":"16_47361303","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00125-011-2447-3","volume":"55","year":"2012","journal-title":"Diabetologia","ISSN":"https:\/\/id.crossref.org\/issn\/0012-186X","issn-type":"print"},{"key":"17_47567474","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/ncomms2537","volume":"4","year":"2013","journal-title":"NATURE COMMUNICATIONS"},{"issue":"2","key":"18_9411607","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0014-5793(91)80182-3","volume":"279","author":"Fehmann","year":"1991","journal-title":"FEBS Letters","ISSN":"https:\/\/id.crossref.org\/issn\/1873-3468","issn-type":"print"},{"issue":"10","key":"19_28559590","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1021\/jm070104l","volume":"50","author":"Feng","year":"2007","journal-title":"Journal of medicinal chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0022-2623","issn-type":"print"},{"issue":"90001","key":"20_18016767","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.2337\/diabetes.53.2007.S43","volume":"53","author":"Ferre","year":"2004","journal-title":"Diabetes","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1797","issn-type":"print"},{"key":"21_47567475","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cmet.2010.03.005","volume":"11","year":"2010","journal-title":"CELL METABOLISM"},{"key":"22_47567476","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1111\/j.1463-1326.2011.01460.x","volume":"13","year":"2011","journal-title":"DIABETES OBESITY METABOLISM"},{"issue":"1","key":"23_38873444","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.bbrc.2010.12.021","volume":"404","author":"Kawashima","year":"2011","journal-title":"Biochemical and biophysical research communications","ISSN":"https:\/\/id.crossref.org\/issn\/0006-291X","issn-type":"print"},{"issue":"90001","key":"24_18016769","doi-asserted-by":"publisher","first-page":"S60","DOI":"10.2337\/diabetes.53.2007.S60","volume":"53","author":"Kim","year":"2004","journal-title":"Diabetes","ISSN":"https:\/\/id.crossref.org\/issn\/0012-1797","issn-type":"print"},{"issue":"1-3","key":"25_31610821","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.ejphar.2008.04.047","volume":"589","author":"Lee","year":"2008","journal-title":"European journal of pharmacology","ISSN":"https:\/\/id.crossref.org\/issn\/0014-2999","issn-type":"print"},{"issue":"15","key":"26_19305780","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1101\/gad.1341005","volume":"19","author":"Lehrke","year":"2005","journal-title":"Genes &amp; Development","ISSN":"https:\/\/id.crossref.org\/issn\/0890-9369","issn-type":"print"},{"issue":"7","key":"27_22334026","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1172\/JCI29044","volume":"116","author":"Long","year":"2006","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"issue":"4","key":"28_36066291","doi-asserted-by":"crossref","first-page":"509","DOI":"10.33549\/physiolres.931852","volume":"59","author":"Markova","year":"2010","journal-title":"Physiological research \/ Academia Scientiarum Bohemoslovaca","ISSN":"https:\/\/id.crossref.org\/issn\/0862-8408","issn-type":"print"},{"issue":"9626","key":"29_31181221","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1016\/S0140-6736(08)60768-0","volume":"371","author":"Mazzone","year":"2008","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"issue":"6","key":"30_17087440","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1210\/jc.87.6.2784","volume":"87","author":"Miyazaki","year":"2002","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"2-3","key":"31_31309875","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.ejphar.2008.04.018","volume":"588","author":"Moritoh","year":"2008","journal-title":"European journal of pharmacology","ISSN":"https:\/\/id.crossref.org\/issn\/0014-2999","issn-type":"print"},{"issue":"2-3","key":"32_32749481","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.ejphar.2008.11.017","volume":"602","author":"Moritoh","year":"2009","journal-title":"European journal of pharmacology","ISSN":"https:\/\/id.crossref.org\/issn\/0014-2999","issn-type":"print"},{"issue":"13","key":"33_30700437","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1001\/jama.299.13.1561","volume":"299","year":"2008","journal-title":"JAMA","ISSN":"https:\/\/id.crossref.org\/issn\/0098-7484","issn-type":"print"},{"issue":"6698","key":"34_6155641","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/25931","volume":"395","author":"Nolte","year":"1998","journal-title":"Nature; Physical Science (London)","ISSN":"https:\/\/id.crossref.org\/issn\/1476-4687","issn-type":"print"},{"key":"35_46963950","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.cmet.2012.01.019","volume":"15","year":"2012","journal-title":"CELL METABOLISM"},{"issue":"4","key":"36_10444473","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1172\/JCI10843","volume":"106","author":"Olefsky","year":"2000","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"key":"37_47567477","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1463-1326.2008.01016.x","volume":"11","year":"2009","journal-title":"DIABETES OBESITY METABOLISM"},{"issue":"10","key":"38_35460277","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1185\/03007990903156111","volume":"25","author":"Pratley","year":"2009","journal-title":"Current medical research and opinion","ISSN":"https:\/\/id.crossref.org\/issn\/0300-7995","issn-type":"print"},{"key":"39_40809687","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/j.1463-1326.2010.01237.x","volume":"12","year":"2010","journal-title":"DIABETES OBESITY METABOLISM"},{"issue":"11","key":"40_22457414","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.1194\/jlr.M600248-JLR200","volume":"47","year":"2006","journal-title":"The Journal of Lipid Research","ISSN":"https:\/\/id.crossref.org\/issn\/0022-2275","issn-type":"print"},{"issue":"5","key":"41_6368224","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S0272-6386(99)70035-1","volume":"34","author":"Ritz","year":"1999","journal-title":"American journal of kidney diseases : the official journal of the National Kidney Foundation","ISSN":"https:\/\/id.crossref.org\/issn\/0272-6386","issn-type":"print"},{"key":"42_45881868","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1007\/s00125-009-1300-4","volume":"52","year":"2009","journal-title":"Diabetologia","ISSN":"https:\/\/id.crossref.org\/issn\/0012-186X","issn-type":"print"},{"issue":"41","key":"43_19550657","doi-asserted-by":"publisher","first-page":"37731","DOI":"10.1074\/jbc.R100034200","volume":"276","year":"2001","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"key":"44_47567478","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/j.1463-1326.2009.01124.x","volume":"11","year":"2009","journal-title":"DIABETES OBESITY METABOLISM"},{"issue":"11","key":"45_37921693","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.2337\/dc10-0159","volume":"33","year":"2010","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"issue":"5","key":"46_42051313","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/j.cell.2012.02.017","volume":"148","author":"Samuel","year":"2012","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"issue":"7","key":"47_16256941","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1128\/MCB.16.7.3410","volume":"16","author":"Sears","year":"1996","journal-title":"Molecular and Cellular Biology","ISSN":"https:\/\/id.crossref.org\/issn\/0270-7306","issn-type":"print"},{"issue":"8","key":"48_18267499","doi-asserted-by":"publisher","first-page":"3925","DOI":"10.1210\/en.2004-0321","volume":"145","year":"2004","journal-title":"Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0013-7227","issn-type":"print"},{"issue":"3","key":"49_21651810","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1172\/JCI28003","volume":"116","author":"Semple","year":"2006","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"issue":"21","key":"50_41024067","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1161\/CIRCULATIONAHA.111.041418","volume":"124","year":"2011","journal-title":"Circulation","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7322","issn-type":"print"},{"issue":"2","key":"51_23074361","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1210\/jc.2006-1268","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"key":"52_47567479","doi-asserted-by":"crossref","first-page":"e63626","DOI":"10.1371\/journal.pone.0063626","volume":"8","year":"2013","ISSN":"https:\/\/id.crossref.org\/issn\/1932-6203","issn-type":"print"},{"issue":"9","key":"53_6139756","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.2337\/diacare.21.9.1470","volume":"21","author":"Shimizu","year":"1998","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"key":"54_47567480","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1124\/jpet.107.135723","volume":"325","year":"2008","journal-title":"JOURNAL OF PHAMACOLOGY AND EXPERIMENTAL THERAPEUTICS"},{"key":"55_28203704","first-page":"E299","volume":"270","year":"1996","journal-title":"American Journal of Physiology -- Legacy Content","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9513","issn-type":"print"},{"issue":"1","key":"56_16687659","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1063\/1.365801","volume":"82","author":"Winder","year":"1997","journal-title":"Journal of Applied Physiology","ISSN":"https:\/\/id.crossref.org\/issn\/0021-8987","issn-type":"print"},{"key":"57_47541001","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1463-1326.2010.01354.x","volume":"13","year":"2011","journal-title":"DIABETES OBESITY METABOLISM"}],"container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/221\/1\/133.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/221\/1\/133.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:25Z","timestamp":1784555665000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/221\/1\/133-144\/22618"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4]]},"references-count":57,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/joe-13-0601","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4]]}}}