Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA.
J Investig Med. 2011 Apr;59(4):661-7. doi: 10.2310/JIM.0b013e31820ee432.
Our recent study defined the chemokine-induced human monocyte signaling under normoglycemic condition. To explore the hyperglycemia-induced monocyte signaling, we performed adhesion, migration, and transmigration assays on human monocytes obtained from THP-1 cell line in the presence of normal (5 mM) and high (10 and 20 mM) glucose concentrations without chemokines. We observed augmented (P < 0.01) monocyte adhesion to human umbilical vein endothelial cell monolayer at 10 than 5 mM glucose with no further increase at 20-mM glucose concentration (P < 0.07 vs 10 mM; P < 0.01 vs 5 mM). But incremental increases in monocyte migration (P < 0.01), transmigration (P < 0.01), and stress fiber response (P < 0.01) were observed at 10- and 20-mM glucose concentrations in comparison to 5-mM glucose concentrations. We found gradational increase (P < 0.01) in phosphorylation of Akt(S473) and glycogen synthase kinase (GSK3β(S9)) in hyperglycemia (10 and 20 mM) when compared with 5 mM glucose. Furthermore, hyperglycemia (both 10 and 20 mM)-treated monocyte showed up-regulated phosphorylation of p101 and p110γ subunits of PI-3 kinase in comparison to 5 mM glucose. Hyperglycemia-induced monocyte migration was restored to basal levels in the presence of PI-3 kinase inhibitor, LY. These observations imply that modest hyperglycemia per se, as is commonly observed in diabetic individuals, is a potent stimulator of monocyte activity even without chemokines.
我们最近的研究定义了在正常血糖条件下趋化因子诱导的人单核细胞信号。为了探索高血糖诱导的单核细胞信号，我们在没有趋化因子的情况下，在正常（5mM）和高（10 和 20mM）葡萄糖浓度下，使用 THP-1 细胞系获得的人单核细胞进行黏附、迁移和穿越实验。我们观察到，在 10mM 葡萄糖下，单核细胞与人脐静脉内皮细胞单层的黏附增加（P < 0.01），而在 20mM 葡萄糖浓度下没有进一步增加（P < 0.07 比 10mM；P < 0.01 比 5mM）。但是，在 10-和 20mM 葡萄糖浓度下，单核细胞迁移（P < 0.01）、穿越（P < 0.01）和应激纤维反应（P < 0.01）的增加幅度递增。与 5mM 葡萄糖相比，我们发现高血糖（10 和 20mM）时 Akt（S473）和糖原合酶激酶（GSK3β（S9））的磷酸化呈梯度增加（P < 0.01）。此外，与 5mM 葡萄糖相比，高血糖（10 和 20mM）处理的单核细胞显示 PI-3 激酶的 p101 和 p110γ 亚基的磷酸化上调。在存在 PI-3 激酶抑制剂 LY 的情况下，高血糖诱导的单核细胞迁移恢复到基础水平。这些观察结果表明，适度的高血糖本身，如糖尿病患者中常见的那样，即使没有趋化因子，也是单核细胞活性的强有力刺激物。
