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However, its role in diabetic cardiomyopathy remains unclear. We explored the underlying function and mechanism of PHLPP1 in diabetic cardiomyopathy (DCM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In vivo<jats:italic>,<\/jats:italic> Type 1 diabetic rats were induced by intraperitoneal injection of 60\u00a0mg\/kg streptozotocin (STZ). Lentivirus\u2010mediated short hairpin RNA (shRNA) was used to knock down the expression of PHLPP1. In vitro, primary neonatal rat cardiomyocytes and H9C2 cells were incubated in 5.5\u00a0mmol\/L glucose (normal glucose, NG) or 33.3\u00a0mmol\/L glucose (high glucose, HG). PHLPP1 expression was inhibited by PHLPP1\u2010siRNA to probe into the function of PHLPP1 in high glucose\u2010induced apoptosis in H9c2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Diabetic rats showed up\u2010regulated PHLPP1 expression, left ventricular dysfunction, increased myocardial apoptosis and fibrosis. PHLPP1 inhibition alleviated cardiac dysfunction. Additionally, PHLPP1 inhibition significantly reduced HG\u2010induced apoptosis and restored PI3K\/AKT\/mTOR pathway activity in H9c2 cells. Furthermore, pretreatment with LY294002, an inhibitor of PI3K\/Akt\/mTOR pathway, abolished the anti\u2010apoptotic effect of PHLPP1 inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study indicated that PHLPP1 inhibition alleviated cardiac dysfunction via activating the PI3K\/Akt\/mTOR signalling pathway in DCM. Therefore, PHLPP1 may be a novel therapeutic target for human DCM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcmm.15123","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T21:06:05Z","timestamp":1583787965000},"page":"4612-4623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Inhibition of PHLPP1 ameliorates cardiac dysfunction via activation of the PI3K\/Akt\/mTOR signalling pathway in diabetic cardiomyopathy"],"prefix":"10.1111","volume":"24","author":[{"given":"Mingjun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine Qilu Hospital of Shandong University Jinan 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