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2016 ; 5
(6
): 404-414
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A comprehensive lipidomic screen of pancreatic ?-cells using mass spectroscopy
defines novel features of glucose-stimulated turnover of neutral lipids,
sphingolipids and plasmalogens
#MMPMID27257600
Pearson GL
; Mellett N
; Chu KY
; Boslem E
; Meikle PJ
; Biden TJ
Mol Metab
2016[Jun]; 5
(6
): 404-414
PMID27257600
show ga
OBJECTIVE: Glucose promotes lipid remodelling in pancreatic ?-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 ?-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.