A dipeptidyl peptidase-4 inhibitor suppresses macrophage foam cell formation in diabetic db/db mice and type 2 diabetes patients
A dipeptidyl peptidase-4 inhibitor suppresses macrophage foam cell formation in diabetic db/db mice and type 2 diabetes patients
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二肽基肽酶 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
DOI：
10.1155/2018/8458304
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发表时间：
2018
影响因子：
2.8
通讯作者：
Hirano T
中科院分区：
文献类型：
--
作者：
Terasaki M;Hiromura M;Mori Y;Kohashi K;Kushima H;Koshibu M;Saito T;Yashima H;Watanabe T;Hirano T
二肽基肽酶-4(DPP-4)抑制剂除了具有降血糖作用外，还具有抗动脉粥样硬化的作用。由于巨噬细胞泡沫细胞是动脉粥样硬化的关键成分，我们在体外研究了DPP-4抑制剂替利脂对糖尿病小鼠(C57BLKS/J Iar-+Leprdb/+Leprdb/+Leprdb)和2型糖尿病(T2D)患者巨噬细胞泡沫细胞形成及其相关基因表达水平的影响。我们用氧化型低密度脂蛋白在替利脂蛋白(10 /L)存在或不存在的情况下与培养7天的小鼠腹膜巨噬细胞和人单核细胞来源的巨噬细胞孵育18小时。我们观察到，在糖尿病/糖尿病小鼠(32%)和T2D患者(38%)分离的巨噬细胞中，Tenigliptin显著抑制泡沫细胞的形成；这种作用伴随着CD36(db/db小鼠，43%；T2D患者，46%)和酰基辅酶A：胆固醇酰基转移酶-1(ACAT-1)基因表达水平的降低(db/db小鼠，47%；T2D患者，45%)。这种作用的分子机制与替利脂蛋白下调CD36和ACAT-1有关。DPP-4抑制剂对T2D患者泡沫细胞形成的抑制作用在不同物种之间是保守的，值得研究以阐明其作为T2D患者抗动脉粥样硬化的干预措施的潜力。
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 diabeticdb/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 treatmentex vivoin macrophages isolated from diabeticdb/dbmice (32%) and T2D patients (38%); this effect was accompanied by a reduction of CD36 (db/dbmice, 43%; T2D patients, 46%) and acyl‐coenzyme A: cholesterol acyltransferase‐1 (ACAT‐1) gene expression levels (db/dbmice, 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.