Effect of hyperglycemia on human monocyte activation.

Publication Type:

Journal Article


Journal of investigative medicine : the official publication of the American Federation for Clinical Research, Volume 59, Issue 4, p.661-7 (2011)


Cell Adhesiondigestive disease, digestive deseases Cell Linedigestive disease, digestive deseases Cell Movementdigestive disease, digestive deseases Elafindigestive disease, digestive deseases Endothelium, Vasculardigestive disease, digestive deseases Glucosedigestive disease, digestive deseases Glycogen Synthase Kinase 3digestive disease, digestive deseases Humansdigestive disease, digestive deseases Hyperglycemiadigestive disease, digestive deseases Monocytesdigestive disease, digestive deseases Phosphorylationdigestive disease, digestive deseases Proto-Oncogene Proteins c-aktdigestive disease, digestive deseases Signal Transductiondigestive disease, digestive deseases Umbilical Veins


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.