TY - JOUR T1 - Effect of Hyperglycemia on Human Monocyte Activation JF - Journal of Investigative Medicine JO - J Investig Med SP - 661 LP - 667 DO - 10.2310/JIM.0b013e31820ee432 VL - 59 IS - 4 AU - Debashis Nandy AU - Rajiv Janardhanan AU - Debabrata Mukhopadhyay AU - Ananda Basu Y1 - 2011/04/01 UR - http://hw-f5-jim.highwire.org/content/59/4/661.abstract N2 - 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 (GSK3βS9) 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. ER -