Abstract:
OBJECTIVE: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.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Pearson GL,Mellett N,Chu KY,Boslem E,Meikle PJ,Biden TJdoi
10.1016/j.molmet.2016.04.003subject
Has Abstractpub_date
2016-04-13 00:00:00pages
404-414issue
6issn
2212-8778pii
S2212-8778(16)30020-5journal_volume
5pub_type
杂志文章abstract:BACKGROUND:While additional research is needed, a number of large epidemiological studies show an association between circadian disruption and metabolic disorders. Specifically, obesity, insulin resistance, cardiovascular disease, and other signs of metabolic syndrome all have been linked to circadian disruption in hum...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2015.12.006
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journal_title:Molecular metabolism
pub_type: 杂志文章
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journal_title:Molecular metabolism
pub_type: 杂志文章
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.02.001
更新日期:2014-03-12 00:00:00
abstract::Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) resulting in superior body weight lowering to selective GLP1R agonists. OXM reduces food intake and increases energy expenditure in hum...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2013.12.001
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.02.006
更新日期:2015-03-03 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.05.001
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2020.01.001
更新日期:2020-05-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
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journal_title:Molecular metabolism
pub_type: 杂志文章
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.06.002
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101052
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2019.10.002
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.11.006
更新日期:2019-02-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.01.002
更新日期:2020-04-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.10.003
更新日期:2016-10-24 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.11.010
更新日期:2018-02-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.06.002
更新日期:2015-06-15 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2017.06.019
更新日期:2017-07-08 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.07.009
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2016.05.016
更新日期:2016-06-06 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.12.004
更新日期:2019-02-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.04.008
更新日期:2014-05-02 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.12.014
更新日期:2018-03-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.05.006
更新日期:2017-05-15 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101157
更新日期:2020-12-24 00:00:00
abstract:BACKGROUND:Poly-ADP-ribose polymerases (PARPs) are key mediators of cellular stress response. They are intimately linked to cellular metabolism through the consumption of NAD+. PARP1/ARTD1 in the nucleus is the major NAD+ consuming activity and plays a key role in maintaining genomic integrity. SCOPE OF REVIEW:In this...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2020.01.014
更新日期:2020-08-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.09.005
更新日期:2017-12-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.08.003
更新日期:2017-11-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.01.003
更新日期:2017-01-12 00:00:00