首页> 美国卫生研究院文献>International Journal of Endocrinology >A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in Diabetic db/db Mice and Type 2 Diabetes Patients
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A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in Diabetic db/db Mice and Type 2 Diabetes Patients

机译:Depteptidyl Peptidase-4抑制剂抑制糖尿病db / db小鼠和2型糖尿病患者的巨噬细胞泡沫细胞形成。

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摘要

Dipeptidyl peptidase-4 (DPP-4) inhibitors could have antiatherosclerotic action, in addition to antihyperglycemic roles. Because macrophage foam cells are key components of atherosclerosis, we investigated the effect of the DPP-4 inhibitor teneligliptin on foam cell formation and its related gene expression levels in macrophages extracted from diabetic db/db (C57BLKS/J Iar -+Leprdb/+Leprdb) mice and type 2 diabetes (T2D) patients ex vivo. We incubated mouse peritoneal macrophages and human monocyte-derived macrophages differentiated by 7-day culture with oxidized low-density lipoprotein in the presence/absence of teneligliptin (10 nmol/L) for 18 hours. We observed remarkable suppression of foam cell formation by teneligliptin treatment ex vivo in macrophages isolated from diabetic db/db mice (32%) and T2D patients (38%); this effect was accompanied by a reduction of CD36 (db/db mice, 43%; T2D patients, 46%) and acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) gene expression levels (db/db mice, 47%; T2D patients, 45%). Molecular mechanisms underlying this effect are associated with downregulation of CD36 and ACAT-1 by teneligliptin. The suppressive effect of a DPP-4 inhibitor on foam cell formation in T2D is conserved across species and is worth studying to elucidate its potential as an intervention for antiatherogenesis in T2D patients.
机译:二肽基肽酶-4(DPP-4)抑制剂除了具有降血糖作用外,还可以具有抗动脉粥样硬化作用。因为巨噬细胞泡沫细胞是动脉粥样硬化的关键组成部分,所以我们研究了DPP-4抑制剂替尼利列汀对从糖尿病db / db提取的巨噬细胞中泡沫细胞形成及其相关基因表达水平的影响(C57BLKS / J Iar-+ Lepr db / + Lepr db )小鼠和2型糖尿病(T2D)患者离体。我们在存在/不存在替加列汀(10μnmol/ L)的情况下,将小鼠腹膜巨噬细胞和人单核细胞衍生的巨噬细胞与氧化的低密度脂蛋白进行7天培养,孵育18小时。我们观察到在分离自糖尿病db / db小鼠(32%)和T2D患者(38%)的巨噬细胞中,通过Teneligliptin离体处理显着抑制了泡沫细胞形成。这种作用伴随着CD36(db / db小鼠,43%; T2D患者,46%)和酰基辅酶A的降低:胆固醇酰基转移酶-1(ACAT-1)基因表达水平(db / db小鼠,47% ; T2D患者,占45%)。特立格列汀下调这种作用的分子机制与CD36和ACAT-1的下调有关。 DPP-4抑制剂对T2D中泡沫细胞形成的抑制作用在整个物种中均保持不变,值得研究以阐明其作为T2D患者抗动脉粥样硬化干预的潜力。

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