A comprehensive lipidomic screen of pancreatic beta-cells using mass spectroscopy defines novel features of glucose-stimulated turnover of neutral lipids, sphingolipids and plasmalogens

作者：Pearson Gemma L; Mellett Natalie; Chu Kwan Yi; Boslem Ebru; Meikle Peter J^*; Biden Trevor J^*

来源：Molecular Metabolism, 2016, 5(6): 404-414.

DOI：10.1016/j.molmet.2016.04.003

• Pancreatic beta-cell
• Insulin secretion
• Diacylglycerol
• Monacylglycerol
• Ceramide
• Plasmalogen

Objective: Glucose promotes lipid remodelling in pancreatic beta-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 beta-cells and isolated mouse islets following 1 h stimulation with glucose. Flux through sphingolipid pathways was also assessed in H-3-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.

• 出版日期2016-6
• 单位河北医科大学