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http://purl.uniprot.org/citations/33090289http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33090289http://www.w3.org/2000/01/rdf-schema#comment"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-IIIβ (PI4KIIIβ) 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 PI4KIIIβ is involved in myocellular GLUT4 translocation induced by contraction or oligomycin (an F1F0-ATP synthase inhibitor that activates contraction-like signaling). Pharmacological targeting, with compound MI14, or genetic silencing of PI4KIIIβ inhibited contraction/oligomycin-stimulated GLUT4 translocation and glucose uptake in cardiomyocytes but did not affect CD36 translocation nor LCFA uptake. Addition of the PI4KIIIβ enzymatic reaction product phosphatidylinositol-4-phosphate restored oligomycin-stimulated glucose uptake in the presence of MI14. PI4KIIIβ activation by PKD1 involves Ser294 phosphorylation and altered its localization with unchanged enzymatic activity. Adenoviral PI4KIIIβ overexpression stimulated glucose uptake, but did not activate hypertrophic signaling, indicating that unlike PKD1, PI4KIIIβ is selectively involved in GLUT4 translocation. Finally, PI4KIIIβ overexpression prevented insulin resistance and contractile dysfunction in lipid-overexposed cardiomyocytes. Together, our studies identify PI4KIIIβ as positive and selective regulator of GLUT4 translocation in response to contraction-like signaling, suggesting PI4KIIIβ as a promising target to rescue defective glucose uptake in diabetics."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.org/dc/terms/identifier"doi:10.1007/s00018-020-03669-7"xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Wang S."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Neumann D."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Wong L."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Sun A."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Simsek Papur O."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Glatz J.F.C."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Luiken J.J.F.P."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Strzelecka A."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Nabben M."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Dirkx E."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/author"Sips T."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/name"Cell Mol Life Sci"xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/pages"2839-2856"xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/title"Phosphatidylinositol 4-kinase IIIbeta mediates contraction-induced GLUT4 translocation and shows its anti-diabetic action in cardiomyocytes."xsd:string
http://purl.uniprot.org/citations/33090289http://purl.uniprot.org/core/volume"78"xsd:string
http://purl.uniprot.org/citations/33090289http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33090289
http://purl.uniprot.org/citations/33090289http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33090289
http://purl.uniprot.org/uniprot/#_A0A0B4J1S8-mappedCitation-33090289http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33090289
http://purl.uniprot.org/uniprot/#_Q9UBF8-mappedCitation-33090289http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33090289
http://purl.uniprot.org/uniprot/A0A0B4J1S8http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33090289
http://purl.uniprot.org/uniprot/Q9UBF8http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/33090289