| http://purl.uniprot.org/citations/23839933 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23839933 | http://www.w3.org/2000/01/rdf-schema#comment | "Lipotoxic stress-induced β-cell death (lipotoxicity) is recognized as a key contributor to the development of type 2 diabetes mellitus (T2DM). The current study reports a critical role of sphingosine kinase 1 (SphK1) in β-cell survival under lipotoxic conditions. In an attempt to investigate the role of SphK1 in lipotoxicity in vivo, we fed Sphk1(-/-) and wild-type (WT) mice with a high-fat diet (HFD) or normal chow diet. Remarkably, while HFD-fed WT mice developed glucose intolerance and compensatory hyperinsulinemia, all HFD-fed Sphk1(-/-) mice manifested evident diabetes, accompanied by a nearly 3-fold reduction in insulin levels compared with the WT mice. Pancreatic β-cell mass was increased by 140% in HFD-fed WT mice but decreased to 50% in HFD-fed Sphk1(-/-) mice, in comparison with the chow diet control groups, respectively. Accordingly, by blocking the enzyme activity, expression of a dominant negative form of SphK1 markedly promoted palmitate-induced cell death in MIN6 and INS-1 β-cell lines. Moreover, primary islets isolated from Sphk1(-/-) mice exhibited higher susceptibility to lipotoxicity than WT controls. Of note, sphingosine 1-phosphate (S1P) profoundly abrogated lipotoxicity in β cells or the cells lacking SphK1 activity and Sphk1(-/-) islets, highlighting a pivotal role of S1P in β-cell survival under lipotoxic conditions. These findings could suggest a new therapeutic strategy for preventing β-cell death and thus the onset of T2DM."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.org/dc/terms/identifier | "doi:10.1096/fj.13-230052"xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/author | "Qi Y."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/author | "Xia P."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/author | "Vadas M."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/author | "Don A."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/author | "Lay A."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/name | "FASEB J"xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/pages | "4294-4304"xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/title | "Loss of sphingosine kinase 1 predisposes to the onset of diabetes via promoting pancreatic beta-cell death in diet-induced obese mice."xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://purl.uniprot.org/core/volume | "27"xsd:string |
| http://purl.uniprot.org/citations/23839933 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23839933 |
| http://purl.uniprot.org/citations/23839933 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23839933 |
| http://purl.uniprot.org/uniprot/#_B1AT85-mappedCitation-23839933 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23839933 |
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| http://purl.uniprot.org/uniprot/#_B1AT88-mappedCitation-23839933 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23839933 |
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