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dc.contributor.authorPearson, GL
dc.contributor.authorMellett, N
dc.contributor.authorChu, KY
dc.contributor.authorBoslem, E
dc.contributor.authorMeikle, PJ
dc.contributor.authorBiden, TJ
dc.date.accessioned2021-02-04T00:26:23Z
dc.date.available2021-02-04T00:26:23Z
dc.date.issued2016-06-01
dc.identifierpii: S2212-8778(16)30020-5
dc.identifier.citationPearson, G. L., Mellett, N., Chu, K. Y., Boslem, E., Meikle, P. J. & Biden, T. J. (2016). A comprehensive lipidomic screen of pancreatic beta-cells using mass spectroscopy defines novel features of glucose-stimulated turnover of neutral lipids, sphingolipids and plasmalogens. MOLECULAR METABOLISM, 5 (6), pp.404-414. https://doi.org/10.1016/j.molmet.2016.04.003.
dc.identifier.issn2212-8778
dc.identifier.urihttp://hdl.handle.net/11343/259108
dc.description.abstractOBJECTIVE: Glucose promotes lipid remodelling in pancreatic β-cells, and this is thought to contribute to the regulation of insulin secretion, but the metabolic pathways and potential signalling intermediates have not been fully elaborated. METHODS: Using mass spectrometry (MS) we quantified changes in approximately 300 lipid metabolites in MIN6 β-cells and isolated mouse islets following 1 h stimulation with glucose. Flux through sphingolipid pathways was also assessed in (3)H-sphinganine-labelled cells using TLC. RESULTS: Glucose specifically activates the conversion of triacylglycerol (TAG) to diacylglycerol (DAG). This leads indirectly to the formation of 18:1 monoacylglycerol (MAG), via degradation of saturated/monounsaturated DAG species, such as 16:0_18:1 DAG, which are the most abundant, immediate products of glucose-stimulated TAG hydrolysis. However, 16:0-containing, di-saturated DAG species are a better direct marker of TAG hydrolysis since, unlike the 18:1-containing DAGs, they are predominately formed via this route. Using multiple reaction monitoring, we confirmed that in islets under basal conditions, 18:1 MAG is the most abundant species. We further demonstrated a novel site of glucose to enhance the conversion of ceramide to sphingomyelin (SM) and galactosylceramide (GalCer). Flux and product:precursor analyses suggest regulation of the enzyme SM synthase, which would constitute a separate mechanism for localized generation of DAG in response to glucose. Phosphatidylcholine (PC) plasmalogen (P) species, specifically those containing 20:4, 22:5 and 22:6 side chains, were also diminished in the presence of glucose, whereas the more abundant phosphatidylethanolamine plasmalogens were unchanged. CONCLUSION: Our results highlight 18:1 MAG, GalCer, PC(P) and DAG/SM as potential contributors to metabolic stimulus-secretion coupling.
dc.languageEnglish
dc.publisherELSEVIER SCIENCE BV
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleA comprehensive lipidomic screen of pancreatic beta-cells using mass spectroscopy defines novel features of glucose-stimulated turnover of neutral lipids, sphingolipids and plasmalogens
dc.typeJournal Article
dc.identifier.doi10.1016/j.molmet.2016.04.003
melbourne.affiliation.departmentBio21
melbourne.affiliation.facultyAffiliate
melbourne.source.titleMolecular Metabolism
melbourne.source.volume5
melbourne.source.issue6
melbourne.source.pages404-414
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1208039
melbourne.contributor.authorMeikle, Peter
dc.identifier.eissn2212-8778
melbourne.accessrightsOpen Access


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