Diabetologia:非诺贝特可增加极长链的鞘脂类物质,改善NOD小鼠的血糖稳态?

2019-12-28 MedSci MedSci原创

非诺贝特改变了胰腺脂质体,使其处于一种更抗炎和抗凋亡的状态。对胰岛交感神经纤维和血糖稳态的有益作用表明,非诺贝特可作为改善血糖稳态和预防糖尿病相关疾病的治疗手段。

鞘脂代谢调节β细胞生物学和炎症,在1糖尿病发病时鞘脂代谢会出现异常。非诺贝特,一种调节鞘脂代谢的物质,在NOD小鼠中有预防糖尿病的作用。在此,我们旨在研究非诺贝特对NOD小鼠胰腺脂质体、胰腺形态、胰腺交感神经和血糖稳态的影响。

我们用非诺贝特治疗3周大的雌性NOD小鼠。采用MS对胰腺进行脂质体分析,用体视学对胰岛体积进行分析。采用酪氨酸羟化酶染色测定胰岛交感神经纤维体积。通过测量12 - 30周的非空腹血糖来评估其对血糖稳态的影响。此外,我们还测量了葡萄糖耐量、空腹胰岛素和胰高血糖素水平以及胰岛素耐量。

我们发现非诺贝特选择性地增加了NOD小鼠胰腺中极长链鞘磷脂的数量。此外,我们发现非诺贝特会导致胰脂质体的重构,增加了溶甘油磷脂的量。非诺贝特不影响胰岛或胰腺的体积,但导致胰岛交感神经纤维和酪氨酸羟化酶阳性细胞的体积增大。非诺贝特处理的NOD小鼠血糖更稳定,这与非空腹血糖降低和空腹血糖升高有关。此外,非诺贝特改善葡萄糖耐量,降低空腹血糖素水平,防止空腹高胰岛素血症。

这些数据表明非诺贝特改变了胰腺脂质体,使其处于一种更抗炎和抗凋亡的状态。对胰岛交感神经纤维和血糖稳态的有益作用表明,非诺贝特可作为改善血糖稳态和预防糖尿病相关疾病的治疗手段。

原始出处:

Laurits J. HolmMartin Haupt-JorgensenFenofibrate increases very-long-chain sphingolipids and improves blood glucose homeostasis in NOD mice

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