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Effect of Hyperglycemia on Human Monocyte Activation
  1. Debashis Nandy, MD*,
  2. Rajiv Janardhanan, PhD,
  3. Debabrata Mukhopadhyay, PhD,
  4. Ananda Basu, MD, FRCP*
  1. From the *Division of Endocrinology and Metabolism, and †Department of Biochemistry & Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN.
  1. Received October 31, 2010, and in revised form January 4, 2011.
  2. Accepted for publication January 4, 2011.
  3. Reprints: Ananda Basu MD, FRCP, 5-193 Joseph, Saint Mary's Hospital, Mayo Clinic College of Medicine, Rochester, MN 55905. E-mail: basu.ananda{at}mayo.edu.
  4. This work was carried out with the support of National Institutes of Health grants HL072178 and HL070567 to D.M. and Mayo Foundation Clinical Research award to A.B.
  5. The authors have nothing to disclose.

Abstract

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.

Key Words
  • hyperglycemia
  • THP-1
  • monocyte
  • p101
  • p110γ

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