{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:30:48Z","timestamp":1787502648229,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"34","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300899"],"award-info":[{"award-number":["82300899"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Statins, the first\u2010line medication for dyslipidemia, are linked to an increased risk of type 2 diabetes. But exactly how statins cause diabetes is yet unknown. In this study, a developed short\u2010term statin therapy on hyperlipidemia mice show that hepatic insulin resistance is a cause of statin\u2010induced diabetes. Statin medication raises the expression of progesterone and adiponectin receptor 9 (PAQR9) in liver, which inhibits insulin signaling through degradation of protein phosphatase, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    \/Mn\n                    <jats:sup>2+<\/jats:sup>\n                    dependent 1 (PPM1\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ) to activate ERK pathway. STIP1 homology and U\u2010box containing protein 1 (STUB1) is found to mediate ubiquitination of PPM1\n                    <jats:italic>\u03b1<\/jats:italic>\n                    promoted by PAQR9. On the other hand, decreased activity of hepatocyte nuclear factor 4 alpha (HNF4\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ) seems to be the cause of PAQR9 expression under statin therapy. The interventions on PAQR9, including deletion of PAQR9, caloric restriction and HNF4\n                    <jats:italic>\u03b1<\/jats:italic>\n                    activation, are all effective treatments for statin\u2010induced diabetes, while liver specific over\u2010expression of PPM1\n                    <jats:italic>\u03b1<\/jats:italic>\n                    is another possible tactic. The results reveal the importance of HNF4\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010PAQR9\u2010STUB1\u2010PPM1\n                    <jats:italic>\u03b1<\/jats:italic>\n                    axis in controlling the statin\u2010induced hepatic insulin resistance, offering a fresh insight into the molecular mechanisms underlying statin therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202403451","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:41:19Z","timestamp":1720226479000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Short\u2010Term Statin Therapy Induces Hepatic Insulin Resistance Through HNF4\n                    <i>\u03b1<\/i>\n                    \/PAQR9\/PPM1\n                    <i>\u03b1<\/i>\n                    Axis Regulated AKT 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