Subjects with low serum HDL cholesterol levels are reported to be susceptible to diabetes, with insulin resistance believed to be the underlying pathological mechanism. Apolipoprotein M (apoM) is a carrier of sphingosine-1-phosphate (S1P), a multifunctional lipid mediator, on HDL, and the pleiotropic effects of HDL are believed to be mediated by S1P. In the current study, we attempted to investigate the potential association between apoM/S1P and insulin resistance. We observed that the serum levels of apoM were lower in patients with type 2 diabetes and that they were negatively correlated with BMI and the insulin resistance index. While deletion of apoM in mice was associated with worsening of insulin resistance, overexpression of apoM was associated with improvement of insulin resistance. Presumably, apoM/S1P exerts its protective effect against insulin resistance by activating insulin signaling pathways, such as the AKT and AMPK pathways, and also by improving the mitochondrial functions through upregulation of SIRT1 protein levels. These actions of apoM/S1P appear to be mediated via activation of S1P1 and/or S1P3. These results suggest that apoM/S1P exerts protective roles against the development of insulin resistance.

中文翻译：

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载脂蛋白 M/1-磷酸鞘氨醇对胰岛素抵抗的保护

据报道，血清 HDL 胆固醇水平低的受试者易患糖尿病，胰岛素抵抗被认为是潜在的病理机制。载脂蛋白 M (apoM) 是 1-磷酸鞘氨醇 (S1P) 的载体，是 HDL 的多功能脂质介质，据信 HDL 的多效作用是由 S1P 介导的。在目前的研究中，我们试图调查 apoM/S1P 与胰岛素抵抗之间的潜在关联。我们观察到 2 型糖尿病患者血清 apoM 水平较低，并且与 BMI 和胰岛素抵抗指数呈负相关。虽然小鼠 apoM 的缺失与胰岛素抵抗的恶化有关，但 apoM 的过度表达与胰岛素抵抗的改善有关。想必，apoM/S1P 通过激活胰岛素信号通路（例如 AKT 和 AMPK 通路）以及通过上调 SIRT1 蛋白水平来改善线粒体功能来发挥其对胰岛素抵抗的保护作用。apoM/S1P 的这些作用似乎是通过 S1P1 和/或 S1P3 的激活介导的。这些结果表明 apoM/S1P 对胰岛素抵抗的发展发挥保护作用。