{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:12:01Z","timestamp":1780549921725,"version":"3.54.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004543","name":"Chinese Scholarship Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dekker grant","award":["2019T041"],"award-info":[{"award-number":["2019T041"]}]},{"DOI":"10.13039\/501100001835","name":"Maastricht University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001835","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell. Mol. Life Sci."],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the diabetic heart, long-chain fatty acid (LCFA) uptake is increased at the expense of glucose uptake. This metabolic shift ultimately leads to insulin resistance and a reduced cardiac function. Therefore, signaling kinases that mediate glucose uptake without simultaneously stimulating LCFA uptake could be considered attractive anti-diabetic targets. Phosphatidylinositol-4-kinase-III\u03b2 (PI4KIII\u03b2) is a lipid kinase downstream of protein kinase D1 (PKD1) that mediates Golgi-to-plasma membrane vesicular trafficking in HeLa-cells. In this study, we evaluated whether PI4KIII\u03b2 is involved in myocellular GLUT4 translocation induced by contraction or oligomycin (an F<jats:sub>1<\/jats:sub>F<jats:sub>0<\/jats:sub>-ATP synthase inhibitor that activates contraction-like signaling). Pharmacological targeting, with compound MI14, or genetic silencing of PI4KIII\u03b2 inhibited contraction\/oligomycin-stimulated GLUT4 translocation and glucose uptake in cardiomyocytes but did not affect CD36 translocation nor LCFA uptake. Addition of the PI4KIII\u03b2 enzymatic reaction product phosphatidylinositol-4-phosphate restored oligomycin-stimulated glucose uptake in the presence of MI14. PI4KIII\u03b2 activation by PKD1 involves Ser294 phosphorylation and altered its localization with unchanged enzymatic activity. Adenoviral PI4KIII\u03b2 overexpression stimulated glucose uptake, but did not activate hypertrophic signaling, indicating that unlike PKD1, PI4KIII\u03b2 is selectively involved in GLUT4 translocation. Finally, PI4KIII\u03b2 overexpression prevented insulin resistance and contractile dysfunction in lipid-overexposed cardiomyocytes. Together, our studies identify PI4KIII\u03b2 as positive and selective regulator of GLUT4 translocation in response to contraction-like signaling, suggesting PI4KIII\u03b2 as a promising target to rescue defective glucose uptake in diabetics.<\/jats:p>","DOI":"10.1007\/s00018-020-03669-7","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T15:07:44Z","timestamp":1603379264000},"page":"2839-2856","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Phosphatidylinositol 4-kinase III\u03b2 mediates contraction-induced GLUT4 translocation and shows its anti-diabetic action in cardiomyocytes"],"prefix":"10.1007","volume":"78","author":[{"given":"A.","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Simsek Papur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Dirkx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Sips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Strzelecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Nabben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. F. C.","family":"Glatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8109-5667","authenticated-orcid":false,"given":"J. J. F. P.","family":"Luiken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"issue":"7285","key":"3669_CR1","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/s0140-6736(63)91500-9","volume":"1","author":"PJ Randle","year":"1963","unstructured":"Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1(7285):785\u2013789. https:\/\/doi.org\/10.1016\/s0140-6736(63)91500-9","journal-title":"Lancet"},{"issue":"1","key":"3669_CR2","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1152\/physrev.00015.2009","volume":"90","author":"GD Lopaschuk","year":"2010","unstructured":"Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC (2010) Myocardial fatty acid metabolism in health and disease. Physiol Rev 90(1):207\u2013258. https:\/\/doi.org\/10.1152\/physrev.00015.2009","journal-title":"Physiol Rev"},{"issue":"7","key":"3669_CR3","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.bbamcr.2011.01.015","volume":"1813","author":"JS Jaswal","year":"2011","unstructured":"Jaswal JS, Keung W, Wang W, Ussher JR, Lopaschuk GD (2011) Targeting fatty acid and carbohydrate oxidation\u2014a novel therapeutic intervention in the ischemic and failing heart. Biochim Biophys Acta 1813(7):1333\u20131350. https:\/\/doi.org\/10.1016\/j.bbamcr.2011.01.015","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"3669_CR4","doi-asserted-by":"publisher","first-page":"165579","DOI":"10.1016\/j.bbadis.2019.165579","volume":"1866","author":"JFC Glatz","year":"2020","unstructured":"Glatz JFC, Nabben M, Young ME, Schulze PC, Taegtmeyer H, Luiken J (2020) Re-balancing cellular energy substrate metabolism to mend the failing heart. Biochim Biophys Acta Mol Basis Dis 1866(5):165579. https:\/\/doi.org\/10.1016\/j.bbadis.2019.165579","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"3669_CR5","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.plefa.2016.06.002","volume":"136","author":"Y Liu","year":"2018","unstructured":"Liu Y, Neumann D, Glatz JFC, Luiken J (2018) Molecular mechanism of lipid-induced cardiac insulin resistance and contractile dysfunction. Prostagland Leukot Essent Fatty Acids 136:131\u2013141. https:\/\/doi.org\/10.1016\/j.plefa.2016.06.002","journal-title":"Prostagland Leukot Essent Fatty Acids"},{"issue":"10","key":"3669_CR6","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.1007\/s00125-015-3691-8","volume":"58","author":"A Bonen","year":"2015","unstructured":"Bonen A, Jain SS, Snook LA, Han XX, Yoshida Y, Buddo KH, Lally JS, Pask ED, Paglialunga S, Beaudoin MS, Glatz JF, Luiken JJ, Harasim E, Wright DC, Chabowski A, Holloway GP (2015) Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats. Diabetologia 58(10):2381\u20132391. https:\/\/doi.org\/10.1007\/s00125-015-3691-8","journal-title":"Diabetologia"},{"issue":"7","key":"3669_CR7","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.2337\/diabetes.53.7.1655","volume":"53","author":"SL Coort","year":"2004","unstructured":"Coort SL, Hasselbaink DM, Koonen DP, Willems J, Coumans WA, Chabowski A, van der Vusse GJ, Bonen A, Glatz JF, Luiken JJ (2004) Enhanced sarcolemmal FAT\/CD36 content and triacylglycerol storage in cardiac myocytes from obese zucker rats. Diabetes 53(7):1655\u20131663. https:\/\/doi.org\/10.2337\/diabetes.53.7.1655","journal-title":"Diabetes"},{"issue":"1","key":"3669_CR8","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1152\/physrev.00003.2009","volume":"90","author":"JF Glatz","year":"2010","unstructured":"Glatz JF, Luiken JJ, Bonen A (2010) Membrane fatty acid transporters as regulators of lipid metabolism: implications for metabolic disease. Physiol Rev 90(1):367\u2013417. https:\/\/doi.org\/10.1152\/physrev.00003.2009","journal-title":"Physiol Rev"},{"issue":"9","key":"3669_CR9","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1007\/s00125-007-0735-8","volume":"50","author":"DM Ouwens","year":"2007","unstructured":"Ouwens DM, Diamant M, Fodor M, Habets DDJ, Pelsers M, El Hasnaoui M, Dang ZC, van den Brom CE, Vlasblom R, Rietdijk A, Boer C, Coort SLM, Glatz JFC, Luiken J (2007) Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification. Diabetologia 50(9):1938\u20131948. https:\/\/doi.org\/10.1007\/s00125-007-0735-8","journal-title":"Diabetologia"},{"issue":"2","key":"3669_CR10","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1172\/JCI10583","volume":"106","author":"GI Shulman","year":"2000","unstructured":"Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106(2):171\u2013176. https:\/\/doi.org\/10.1172\/JCI10583","journal-title":"J Clin Invest"},{"issue":"6","key":"3669_CR11","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.diabet.2007.10.004","volume":"33","author":"B Viollet","year":"2007","unstructured":"Viollet B, Mounier R, Leclerc J, Yazigi A, Foretz M, Andreelli F (2007) Targeting AMP-activated protein kinase as a novel therapeutic approach for the treatment of metabolic disorders. Diabetes Metab 33(6):395\u2013402. https:\/\/doi.org\/10.1016\/j.diabet.2007.10.004","journal-title":"Diabetes Metab"},{"issue":"7","key":"3669_CR12","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.2337\/diabetes.52.7.1627","volume":"52","author":"JJ Luiken","year":"2003","unstructured":"Luiken JJ, Coort SL, Willems J, Coumans WA, Bonen A, van der Vusse GJ, Glatz JF (2003) Contraction-induced fatty acid translocase\/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. Diabetes 52(7):1627\u20131634. https:\/\/doi.org\/10.2337\/diabetes.52.7.1627","journal-title":"Diabetes"},{"issue":"8","key":"3669_CR13","doi-asserted-by":"publisher","first-page":"5871","DOI":"10.1074\/jbc.M111.281881","volume":"287","author":"E Dirkx","year":"2012","unstructured":"Dirkx E, Schwenk RW, Coumans WA, Hoebers N, Angin Y, Viollet B, Bonen A, van Eys GJ, Glatz JF, Luiken JJ (2012) Protein kinase D1 is essential for contraction-induced glucose uptake but is not involved in fatty acid uptake into cardiomyocytes. J Biol Chem 287(8):5871\u20135881. https:\/\/doi.org\/10.1074\/jbc.M111.281881","journal-title":"J Biol Chem"},{"issue":"8","key":"3669_CR14","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.tem.2015.06.002","volume":"26","author":"JJ Luiken","year":"2015","unstructured":"Luiken JJ, Glatz JF, Neumann D (2015) Cardiac contraction-induced GLUT4 translocation requires dual signaling input. Trends Endocrinol Metab 26(8):404\u2013410. https:\/\/doi.org\/10.1016\/j.tem.2015.06.002","journal-title":"Trends Endocrinol Metab"},{"issue":"3","key":"3669_CR15","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.cellsig.2007.11.007","volume":"20","author":"JJ Luiken","year":"2008","unstructured":"Luiken JJ, Vertommen D, Coort SL, Habets DD, El Hasnaoui M, Pelsers MM, Viollet B, Bonen A, Hue L, Rider MH, Glatz JF (2008) Identification of protein kinase D as a novel contraction-activated kinase linked to GLUT4-mediated glucose uptake, independent of AMPK. Cell Signal 20(3):543\u2013556. https:\/\/doi.org\/10.1016\/j.cellsig.2007.11.007","journal-title":"Cell Signal"},{"issue":"1","key":"3669_CR16","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0014-5793(03)00487-3","volume":"546","author":"A Rykx","year":"2003","unstructured":"Rykx A, De Kimpe L, Mikhalap S, Vantus T, Seufferlein T, Vandenheede JR, Van Lint J (2003) Protein kinase D: a family affair. FEBS Lett 546(1):81\u201386. https:\/\/doi.org\/10.1016\/S0014-5793(03)00487-3","journal-title":"FEBS Lett"},{"issue":"11","key":"3669_CR17","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1038\/sj.cdd.4402212","volume":"14","author":"A Eisenberg-Lerner","year":"2007","unstructured":"Eisenberg-Lerner A, Kimchi A (2007) DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress. Cell Death Differ 14(11):1908\u20131915. https:\/\/doi.org\/10.1038\/sj.cdd.4402212","journal-title":"Cell Death Differ"},{"key":"3669_CR18","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.yjmcc.2012.11.005","volume":"55","author":"LKM Steinbusch","year":"2013","unstructured":"Steinbusch LKM, Dirkx E, Hoebers NTH, Roelants V, Foretz M, Viollet B, Diamant M, van Eys G, Ouwens DM, Bertrand L, Glatz JFC, Luiken JJFP (2013) Overexpression of AMP-activated protein kinase or protein kinase D prevents lipid-induced insulin resistance in cardiomyocytes. J Mol Cell Cardiol 55:165\u2013173. https:\/\/doi.org\/10.1016\/j.yjmcc.2012.11.005","journal-title":"J Mol Cell Cardiol"},{"key":"3669_CR19","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.yjmcc.2014.08.017","volume":"76","author":"E Dirkx","year":"2014","unstructured":"Dirkx E, van Eys GJJM, Schwenk RW, Steinbusch LKM, Hoebers N, Coumans WA, Peters T, Janssen BJ, Brans B, Vogg AT, Neumann D, Glatz JFC, Luiken JJFP (2014) Protein kinase-D1 overexpression prevents lipid-induced cardiac insulin resistance. J Mol Cell Cardiol 76:208\u2013217. https:\/\/doi.org\/10.1016\/j.yjmcc.2014.08.017","journal-title":"J Mol Cell Cardiol"},{"issue":"6","key":"3669_CR20","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.tips.2006.04.003","volume":"27","author":"QMJ Wang","year":"2006","unstructured":"Wang QMJ (2006) PKD at the crossroads of DAG and PKC signaling. Trends Pharmacol Sci 27(6):317\u2013323. https:\/\/doi.org\/10.1016\/j.tips.2006.04.003","journal-title":"Trends Pharmacol Sci"},{"issue":"1","key":"3669_CR21","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/emboj\/cdg009","volume":"22","author":"P Storz","year":"2003","unstructured":"Storz P, Toker A (2003) Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. EMBO J 22(1):109\u2013120. https:\/\/doi.org\/10.1093\/emboj\/cdg009","journal-title":"EMBO J"},{"issue":"2","key":"3669_CR22","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1161\/CIRCRESAHA.107.168211","volume":"102","author":"M Avkiran","year":"2008","unstructured":"Avkiran M, Rowland AJ, Cuello F, Haworth RS (2008) Protein kinase D in the cardiovascular system: emerging roles in health and disease. Circ Res 102(2):157\u2013163. https:\/\/doi.org\/10.1161\/CIRCRESAHA.107.168211","journal-title":"Circ Res"},{"issue":"19","key":"3669_CR23","doi-asserted-by":"publisher","first-page":"8374","DOI":"10.1128\/MCB.24.19.8374-8385.2004","volume":"24","author":"RB Vega","year":"2004","unstructured":"Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA (2004) Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5. Mol Cell Biol 24(19):8374\u20138385. https:\/\/doi.org\/10.1128\/MCB.24.19.8374-8385.2004","journal-title":"Mol Cell Biol"},{"issue":"9","key":"3669_CR24","doi-asserted-by":"publisher","first-page":"880\u2013U824","DOI":"10.1038\/ncb1289","volume":"7","author":"A Hausser","year":"2005","unstructured":"Hausser A, Storz P, Martens S, Link G, Toker A, Pfizenmaier K (2005) Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase III beta at the Golgi complex. Nat Cell Biol 7(9):880\u2013U824. https:\/\/doi.org\/10.1038\/ncb1289","journal-title":"Nat Cell Biol"},{"issue":"3","key":"3669_CR25","doi-asserted-by":"publisher","first-page":"E536","DOI":"10.1152\/ajpendo.90353.2008","volume":"295","author":"A Shisheva","year":"2008","unstructured":"Shisheva A (2008) Phosphoinositides in insulin action on GLUT4 dynamics: not just PtdIns(3,4,5)P-3. Am J Physiol Endocrinol Metab 295(3):E536\u2013E544. https:\/\/doi.org\/10.1152\/ajpendo.90353.2008","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"Pt 17","key":"3669_CR26","doi-asserted-by":"publisher","first-page":"3613","DOI":"10.1242\/jcs.03104","volume":"119","author":"A Hausser","year":"2006","unstructured":"Hausser A, Link G, Hoene M, Russo C, Selchow O, Pfizenmaier K (2006) Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III beta protects from dephosphorylation and stabilizes lipid kinase activity. J Cell Sci 119(Pt 17):3613\u20133621. https:\/\/doi.org\/10.1242\/jcs.03104","journal-title":"J Cell Sci"},{"issue":"1","key":"3669_CR27","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jsb.2017.08.006","volume":"200","author":"D Chalupska","year":"2017","unstructured":"Chalupska D, Eisenreichova A, Rozycki B, Rezabkova L, Humpolickova J, Klima M, Boura E (2017) Structural analysis of phosphatidylinositol 4-kinase IIIbeta (PI4KB)\u201414-3-3 protein complex reveals internal flexibility and explains 14-3-3 mediated protection from degradation in vitro. J Struct Biol 200(1):36\u201344. https:\/\/doi.org\/10.1016\/j.jsb.2017.08.006","journal-title":"J Struct Biol"},{"issue":"4","key":"3669_CR28","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/S0022-2275(20)37241-2","volume":"38","author":"JJ Luiken","year":"1997","unstructured":"Luiken JJ, van Nieuwenhoven FA, America G, van der Vusse GJ, Glatz JF (1997) Uptake and metabolism of palmitate by isolated cardiac myocytes from adult rats: involvement of sarcolemmal proteins. J Lipid Res 38(4):745\u2013758","journal-title":"J Lipid Res"},{"issue":"2","key":"3669_CR29","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/0022-2828(91)90103-s","volume":"23","author":"A Volz","year":"1991","unstructured":"Volz A, Piper HM, Siegmund B, Schwartz P (1991) Longevity of adult ventricular rat heart muscle cells in serum-free primary culture. J Mol Cell Cardiol 23(2):161\u2013173. https:\/\/doi.org\/10.1016\/0022-2828(91)90103-s","journal-title":"J Mol Cell Cardiol"},{"issue":"2 Pt 2","key":"3669_CR30","doi-asserted-by":"publisher","first-page":"H212","DOI":"10.1152\/ajpheart.1985.249.2.H212","volume":"249","author":"J Eckel","year":"1985","unstructured":"Eckel J, van Echten G, Reinauer H (1985) Adult cardiac myocytes in primary culture: cell characteristics and insulin-receptor interaction. Am J Physiol 249(2 Pt 2):H212\u2013H221. https:\/\/doi.org\/10.1152\/ajpheart.1985.249.2.H212","journal-title":"Am J Physiol"},{"issue":"10","key":"3669_CR31","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1007\/s00125-010-1832-7","volume":"53","author":"RW Schwenk","year":"2010","unstructured":"Schwenk RW, Dirkx E, Coumans WA, Bonen A, Klip A, Glatz JF, Luiken JJ (2010) Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP-activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes. Diabetologia 53(10):2209\u20132219. https:\/\/doi.org\/10.1007\/s00125-010-1832-7","journal-title":"Diabetologia"},{"issue":"4","key":"3669_CR32","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.3390\/ijms21041520","volume":"21","author":"S Wang","year":"2020","unstructured":"Wang S, Wong L, Neumann D, Liu Y, Sun A, Antoons G, Strzelecka A, Glatz J, Nabben M, Luiken J (2020) Augmenting vacuolar H\u2009+\u2009-ATPase function prevents cardiomyocytes from lipid-overload induced dysfunction. Int J Mol Sci 21(4):1520. https:\/\/doi.org\/10.3390\/ijms21041520","journal-title":"Int J Mol Sci"},{"issue":"10","key":"3669_CR33","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.2337\/diabetes.51.10.3113","volume":"51","author":"JJ Luiken","year":"2002","unstructured":"Luiken JJ, Koonen DP, Willems J, Zorzano A, Becker C, Fischer Y, Tandon NN, Van Der Vusse GJ, Bonen A, Glatz JF (2002) Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT\/CD36. Diabetes 51(10):3113\u20133119. https:\/\/doi.org\/10.2337\/diabetes.51.10.3113","journal-title":"Diabetes"},{"issue":"1","key":"3669_CR34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1042\/BJ20120060","volume":"448","author":"Y Angin","year":"2012","unstructured":"Angin Y, Steinbusch LK, Simons PJ, Greulich S, Hoebers NT, Douma K, van Zandvoort MA, Coumans WA, Wijnen W, Diamant M, Ouwens DM, Glatz JF, Luiken JJ (2012) CD36 inhibition prevents lipid accumulation and contractile dysfunction in rat cardiomyocytes. Biochem J 448(1):43\u201353. https:\/\/doi.org\/10.1042\/BJ20120060","journal-title":"Biochem J"},{"issue":"2","key":"3669_CR35","doi-asserted-by":"publisher","first-page":"E225","DOI":"10.1152\/ajpendo.00655.2013","volume":"307","author":"Y Angin","year":"2014","unstructured":"Angin Y, Schwenk RW, Nergiz-Unal R, Hoebers N, Heemskerk JW, Kuijpers MJ, Coumans WA, van Zandvoort MA, Bonen A, Neumann D, Glatz JF, Luiken JJ (2014) Calcium signaling recruits substrate transporters GLUT4 and CD36 to the sarcolemma without increasing cardiac substrate uptake. Am J Physiol Endocrinol Metab 307(2):E225\u2013E236. https:\/\/doi.org\/10.1152\/ajpendo.00655.2013","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"17","key":"3669_CR36","doi-asserted-by":"publisher","first-page":"8017","DOI":"10.1073\/pnas.91.17.8017","volume":"91","author":"KV Kandror","year":"1994","unstructured":"Kandror KV, Pilch PF (1994) gp160, a tissue-specific marker for insulin-activated glucose transport. PNAS 91(17):8017\u20138021. https:\/\/doi.org\/10.1073\/pnas.91.17.8017","journal-title":"PNAS"},{"issue":"40","key":"3669_CR37","doi-asserted-by":"publisher","first-page":"23612","DOI":"10.1074\/jbc.270.40.23612","volume":"270","author":"SR Keller","year":"1995","unstructured":"Keller SR, Scott HM, Mastick CC, Aebersold R, Lienhard GE (1995) Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles. J Biol Chem 270(40):23612\u201323618. https:\/\/doi.org\/10.1074\/jbc.270.40.23612","journal-title":"J Biol Chem"},{"issue":"Pt 18","key":"3669_CR38","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1242\/jcs.110.18.2281","volume":"110","author":"S Martin","year":"1997","unstructured":"Martin S, Rice JE, Gould GW, Keller SR, Slot JW, James DE (1997) The glucose transporter GLUT4 and the aminopeptidase vp165 colocalise in tubulo-vesicular elements in adipocytes and cardiomyocytes. J Cell Sci 110(Pt 18):2281\u20132291","journal-title":"J Cell Sci"},{"issue":"6","key":"3669_CR39","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.2337\/db16-0727","volume":"66","author":"Y Liu","year":"2017","unstructured":"Liu Y, Steinbusch LKM, Nabben M, Kapsokalyvas D, van Zandvoort M, Schonleitner P, Antoons G, Simons PJ, Coumans WA, Geomini A, Chanda D, Glatz JFC, Neumann D, Luiken J (2017) Palmitate-induced vacuolar-type H(+)-ATPase inhibition feeds forward into insulin resistance and contractile dysfunction. Diabetes 66(6):1521\u20131534. https:\/\/doi.org\/10.2337\/db16-0727","journal-title":"Diabetes"},{"issue":"9","key":"3669_CR40","doi-asserted-by":"publisher","first-page":"3767","DOI":"10.1021\/acs.jmedchem.5b00499","volume":"58","author":"I Mejdrova","year":"2015","unstructured":"Mejdrova I, Chalupska D, Kogler M, Sala M, Plackova P, Baumlova A, Hrebabecky H, Prochazkova E, Dejmek M, Guillon R, Strunin D, Weber J, Lee G, Birkus G, Mertlikova-Kaiserova H, Boura E, Nencka R (2015) Highly selective phosphatidylinositol 4-kinase IIIbeta inhibitors and structural insight into their mode of action. J Med Chem 58(9):3767\u20133793. https:\/\/doi.org\/10.1021\/acs.jmedchem.5b00499","journal-title":"J Med Chem"},{"key":"3669_CR41","doi-asserted-by":"publisher","first-page":"s410","DOI":"10.2741\/1078","volume":"8","author":"SR Keller","year":"2003","unstructured":"Keller SR (2003) The insulin-regulated aminopeptidase: a companion and regulator of GLUT4. Front Biosci 8:s410\u2013s420. https:\/\/doi.org\/10.2741\/1078","journal-title":"Front Biosci"},{"issue":"9","key":"3669_CR42","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/ncb1461","volume":"8","author":"A Gassama-Diagne","year":"2006","unstructured":"Gassama-Diagne A, Yu W, ter Beest M, Martin-Belmonte F, Kierbel A, Engel J, Mostov K (2006) Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells. Nat Cell Biol 8(9):963\u2013970. https:\/\/doi.org\/10.1038\/ncb1461","journal-title":"Nat Cell Biol"},{"issue":"1","key":"3669_CR43","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/embor.2012.183","volume":"14","author":"A Oppelt","year":"2013","unstructured":"Oppelt A, Lobert VH, Haglund K, Mackey AM, Rameh LE, Liestol K, Schink KO, Pedersen NM, Wenzel EM, Haugsten EM, Brech A, Rusten TE, Stenmark H, Wesche J (2013) Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration. EMBO Rep 14(1):57\u201364. https:\/\/doi.org\/10.1038\/embor.2012.183","journal-title":"EMBO Rep"},{"key":"3669_CR44","doi-asserted-by":"publisher","first-page":"23641","DOI":"10.1038\/srep23641","volume":"6","author":"M Klima","year":"2016","unstructured":"Klima M, Toth DJ, Hexnerova R, Baumlova A, Chalupska D, Tykvart J, Rezabkova L, Sengupta N, Man P, Dubankova A, Humpolickova J, Nencka R, Veverka V, Balla T, Boura E (2016) Structural insights and in vitro reconstitution of membrane targeting and activation of human PI4KB by the ACBD3 protein. Sci Rep 6:23641. https:\/\/doi.org\/10.1038\/srep23641","journal-title":"Sci Rep"},{"key":"3669_CR45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.3389\/fcvm.2018.00065","volume":"5","author":"O Simsek Papur","year":"2018","unstructured":"Simsek Papur O, Sun A, Glatz JFC, Luiken J, Nabben M (2018) Acute and chronic effects of protein kinase-D signaling on cardiac energy metabolism. Front Cardiovasc Med 5:65. https:\/\/doi.org\/10.3389\/fcvm.2018.00065","journal-title":"Front Cardiovasc Med"},{"issue":"30","key":"3669_CR46","doi-asserted-by":"publisher","first-page":"27494","DOI":"10.1074\/jbc.M203669200","volume":"277","author":"S Mora","year":"2002","unstructured":"Mora S, Durham PL, Smith JR, Russo AF, Jeromin A, Pessin JE (2002) NCS-1 inhibits insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes through a phosphatidylinositol 4-kinase-dependent pathway. J Biol Chem 277(30):27494\u201327500. https:\/\/doi.org\/10.1074\/jbc.M203669200","journal-title":"J Biol Chem"},{"key":"3669_CR47","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ceb.2019.12.007","volume":"63","author":"GRV Hammond","year":"2020","unstructured":"Hammond GRV, Burke JE (2020) Novel roles of phosphoinositides in signaling, lipid transport, and disease. Curr Opin Cell Biol 63:57\u201367. https:\/\/doi.org\/10.1016\/j.ceb.2019.12.007","journal-title":"Curr Opin Cell Biol"},{"issue":"1","key":"3669_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.plipres.2012.08.003","volume":"52","author":"E Delage","year":"2013","unstructured":"Delage E, Puyaubert J, Zachowski A, Ruelland E (2013) Signal transduction pathways involving phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate: convergences and divergences among eukaryotic kingdoms. Prog Lipid Res 52(1):1\u201314. https:\/\/doi.org\/10.1016\/j.plipres.2012.08.003","journal-title":"Prog Lipid Res"},{"issue":"8","key":"3669_CR49","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1016\/j.bpj.2012.09.015","volume":"103","author":"J Li","year":"2012","unstructured":"Li J, Barylko B, Johnson J, Mueller JD, Albanesi JP, Chen Y (2012) Molecular brightness analysis reveals phosphatidylinositol 4-Kinase IIbeta association with clathrin-coated vesicles in living cells. Biophys J 103(8):1657\u20131665. https:\/\/doi.org\/10.1016\/j.bpj.2012.09.015","journal-title":"Biophys J"},{"issue":"5931","key":"3669_CR50","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1126\/science.1171529","volume":"324","author":"S Vassilopoulos","year":"2009","unstructured":"Vassilopoulos S, Esk C, Hoshino S, Funke BH, Chen CY, Plocik AM, Wright WE, Kucherlapati R, Brodsky FM (2009) A role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism. Science 324(5931):1192\u20131196. https:\/\/doi.org\/10.1126\/science.1171529","journal-title":"Science"},{"key":"3669_CR51","doi-asserted-by":"publisher","first-page":"12148","DOI":"10.1038\/ncomms12148","volume":"7","author":"A Pagliuso","year":"2016","unstructured":"Pagliuso A, Valente C, Giordano LL, Filograna A, Li G, Circolo D, Turacchio G, Marzullo VM, Mandrich L, Zhukovsky MA, Formiggini F, Polishchuk RS, Corda D, Luini A (2016) Golgi membrane fission requires the CtBP1-S\/BARS-induced activation of lysophosphatidic acid acyltransferase delta. Nat Commun 7:12148. https:\/\/doi.org\/10.1038\/ncomms12148","journal-title":"Nat Commun"},{"issue":"6","key":"3669_CR52","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.bbalip.2014.12.011","volume":"1851","author":"A Grabon","year":"2015","unstructured":"Grabon A, Khan D, Bankaitis VA (2015) Phosphatidylinositol transfer proteins and instructive regulation of lipid kinase biology. Biochim Biophys Acta 1851(6):724\u2013735. https:\/\/doi.org\/10.1016\/j.bbalip.2014.12.011","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"3669_CR53","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1194\/jlr.R089730","volume":"60","author":"A Grabon","year":"2019","unstructured":"Grabon A, Bankaitis VA, McDermott MI (2019) The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes. J Lipid Res 60(2):242\u2013268. https:\/\/doi.org\/10.1194\/jlr.R089730","journal-title":"J Lipid Res"},{"issue":"2","key":"3669_CR54","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41580-018-0071-5","volume":"20","author":"LH Wong","year":"2019","unstructured":"Wong LH, Gatta AT, Levine TP (2019) Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes. Nat Rev Mol Cell Biol 20(2):85\u2013101. https:\/\/doi.org\/10.1038\/s41580-018-0071-5","journal-title":"Nat Rev Mol Cell Biol"},{"key":"3669_CR55","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.ceb.2018.04.011","volume":"53","author":"S Cockcroft","year":"2018","unstructured":"Cockcroft S, Raghu P (2018) Phospholipid transport protein function at organelle contact sites. Curr Opin Cell Biol 53:52\u201360. https:\/\/doi.org\/10.1016\/j.ceb.2018.04.011","journal-title":"Curr Opin Cell Biol"},{"issue":"9","key":"3669_CR56","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1111\/j.1600-0854.2010.01085.x","volume":"11","author":"KE Ile","year":"2010","unstructured":"Ile KE, Kassen S, Cao C, Vihtehlic T, Shah SD, Mousley CJ, Alb JG Jr, Huijbregts RP, Stearns GW, Brockerhoff SE, Hyde DR, Bankaitis VA (2010) Zebrafish class 1 phosphatidylinositol transfer proteins: PITPbeta and double cone cell outer segment integrity in retina. Traffic 11(9):1151\u20131167. https:\/\/doi.org\/10.1111\/j.1600-0854.2010.01085.x","journal-title":"Traffic"},{"key":"3669_CR57","doi-asserted-by":"publisher","unstructured":"Xie Z, Hur SK, Zhao L, Abrams CS, Bankaitis VA (2018) A Golgi lipid signaling pathway controls apical Golgi distribution and cell polarity during neurogenesis. Dev Cell 44 (6):725\u2013740 e724. https:\/\/doi.org\/10.1016\/j.devcel.2018.02.025","DOI":"10.1016\/j.devcel.2018.02.025"},{"issue":"8","key":"3669_CR58","doi-asserted-by":"publisher","first-page":"3610","DOI":"10.1093\/nar\/gkv1496","volume":"44","author":"LG Harris","year":"2016","unstructured":"Harris LG, Wang SH, Mani SK, Kasiganesan H, Chou CJ, Menick DR (2016) Evidence for a non-canonical role of HDAC5 in regulation of the cardiac Ncx1 and Bnp genes. Nucleic Acids Res 44(8):3610\u20133617. https:\/\/doi.org\/10.1093\/nar\/gkv1496","journal-title":"Nucleic Acids Res"}],"container-title":["Cellular and Molecular Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-020-03669-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00018-020-03669-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-020-03669-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:12:39Z","timestamp":1634861559000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00018-020-03669-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,22]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["3669"],"URL":"https:\/\/doi.org\/10.1007\/s00018-020-03669-7","relation":{},"ISSN":["1420-682X","1420-9071"],"issn-type":[{"value":"1420-682X","type":"print"},{"value":"1420-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,22]]},"assertion":[{"value":"21 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All animal procedures were approved by the Experimental Animal Committee of Maastricht University, NL.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors agreed to the latest version of this manuscript before submission.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}