Targeted lipidomics reveals associations between serum sphingolipids and insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp

Targeted lipidomics reveals associations between serum sphingolipids and insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp
复制标题

靶向脂质组学揭示血清鞘脂与高胰岛素正常血糖钳测量的胰岛素敏感性之间的关联

DOI:
10.1016/j.diabres.2021.108699
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发表时间:
2021
影响因子:
5.1
通讯作者:
Zhou Hongwen
Zhou Hongwen
中科院分区:
医学3区
文献类型:
--
作者:
Ye Jingya;Ye Xuan;Jiang Wanzi;Lu Chenyan;Geng Xiaomei;Zhao Chenxi;Ma Yizhe;Yang Panpan;Lam Sin Man;Shui Guanghou;Yang Tao;Li John Zhong;Gong Yingyun;Fu Zhenzhen;Zhou Hongwen

文献摘要

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目的鞘磷脂(SPS)及其底物和组成成分脂肪酸(FAs)与多种代谢性疾病的发病机制密切相关。本研究旨在系统地探讨血清鞘脂与胰岛素敏感性及胰岛素分泌的关系。方法采用LC/MS法对86例中国成人血清中不同分子水平的SPS进行脂类组学研究,以稳定状态下30min以上葡萄糖输注速率(GIR30)为指标,用金标准高胰岛素-正常血糖钳夹技术评价胰岛素敏感性。结果血清总皂苷和球三糖神经酰胺(Gb3s)与GIR30呈正相关,游离FAs(FFA 16:1,FFA20:4)、部分长链GM3和复合神经酰胺GluCers与GIR30呈显著负相关。值得注意的是,ROC曲线显示SM/Cer和SM D18:0/26:0可能是胰岛素敏感性诊断指标的良好血脂预测指标,接近于以GIR30为标准诊断标准的常规临床指标,如1/HOMA-IR(曲线下面积=0.80),而(SM/Cer)/(BMI*LDLc)曲线下面积为最佳。结论这些结果提供了血清鞘脂与高胰岛素-正常血糖钳夹测量的胰岛素敏感性之间的新关联,并发现了两个可能代表胰岛素敏感性预后生物标志物的特异性SPS。
AimsSphingolipids(SPs) and their substrates and constituents, fatty acids (FAs), are implicated in the pathogenesis of various metabolic diseases associated. This study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion.MethodsWe conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults using LC/MS. The glucose infusion rate over 30 min (GIR30) was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp. We created the ROC curves to detect the serum SMs diagnostic value.ResultsTotal and subspecies of serum SMs and globotriaosyl ceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (areas under the curve > 0.80) based on GIR30as standard diagnostic criteria, and (SM/Cer)/(BMI*LDLc) areas under the curve = 0.93) is the best.ConclusionsThese results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp and identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.