{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T23:38:31Z","timestamp":1783813111085,"version":"3.55.0"},"reference-count":28,"publisher":"S. Karger AG","issue":"7-8","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2021]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Pioglitazone is a thiazolidinedione oral antidiabetic agent. This study aimed to investigate the effects of pioglitazone as insulin sensitizer on \u03b2-arrestin2 signaling in classical insulin target tissues. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Experiments involved three groups of mice; the first one involved mice fed standard chow diet for 16 weeks; the second one involved mice fed high-fructose, high-fat diet (HFrHFD) for 16 weeks; and the third one involved mice fed HFrHFD for 16 weeks and received pioglitazone (30 mg\/kg\/day, orally) in the last four weeks of feeding HFrHFD. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; The results showed significant improvement in the insulin sensitivity of pioglitazone-treated mice as manifested by significant reduction in the insulin resistance index. This improvement in insulin sensitivity was associated with significant increases in the \u03b2-arrestin2 levels in the adipose tissue, liver, and skeletal muscle. Moreover, pioglitazone significantly increased \u03b2-arrestin2 signaling in all the examined tissues as estimated from significant increases in phosphatidylinositol 4,5 bisphosphate and phosphorylation of Akt at serine 473 and significant decrease in diacylglycerol level. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; To the best of our knowledge, our work reports a new mechanism of action for pioglitazone through which it can enhance the insulin sensitivity. Pioglitazone increases \u03b2-arrestin2 signaling in the adipose tissue, liver, and skeletal muscle of HFrHFD-fed mice. <\/jats:p>","DOI":"10.1159\/000515936","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T21:00:45Z","timestamp":1622754045000},"page":"409-417","source":"Crossref","is-referenced-by-count":5,"title":["Pioglitazone Enhances \u03b2-Arrestin2 Signaling and Ameliorates Insulin Resistance in Classical Insulin Target Tissues"],"prefix":"10.1159","volume":"106","author":[{"given":"Shaimaa","family":"El-Fayoumi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab","family":"Mansour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-0692","authenticated-orcid":false,"given":"Amr","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Fahmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8931-465X","authenticated-orcid":false,"given":"Islam","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.4137\/cmed.s5372"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.6.1364"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.8.1863"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.11.003"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.278"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/nature07617"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1134562"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009191"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31821b1379"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-01883-5"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1177\/1074248420905683"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505649200"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1590\/0004-2730000003141"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2016.05.001"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20198849"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.13232"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-009-0091-1"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001455117"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m800431200"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1769"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.766808"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5245063"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0428"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.012849"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.12288fp"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/srep25912"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102190"}],"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/515936","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/515936","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:39:27Z","timestamp":1745426367000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000515936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":28,"journal-issue":{"issue":"7-8","published-online":{"date-parts":[[2021,7,6]]},"published-print":{"date-parts":[[2021,7,12]]}},"URL":"https:\/\/doi.org\/10.1159\/000515936","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"value":"0031-7012","type":"print"},{"value":"1423-0313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]}}}