Hyperglycemia Acutely Increases Monocyte Extracellular Signal-Regulated Kinase Activityin Vivoin Humans

Giulio Ceolotto, Alessandra Gallo, Michelangelo Sartori, Roberto Valente, Elisabetta Baritono, Andrea Semplicini, Angelo Avogaro
2001 Journal of Clinical Endocrinology and Metabolism  
Glycemic spikes may negatively affect the long-term prognosis of patients with diabetes. Extracellular signal-regulated kinases (ERKs) are intracellular mediators of cell proliferation, and they can be activated in response to high glucose levels. However, the modifications of their activity in response to hyperglycemia have been poorly investigated, in vivo, in humans. Thus, we sought to determine in circulating monocytes: 1) the role of hyperglycemia in ERKs activity and phosphorylation, and
more » ... osphorylation, and 2) whether hyperglycemia affects mitogen-activated protein kinase kinase (MEK) activity and mitogen-activated protein phosphatase-1 (MKP-1) expression. These goals were performed in five normal subjects. Baseline monocyte ERKs activity was 60 Ϯ 5 pmol/min⅐mg protein; when exogenous hyperglycemia was induced, both monocyte ERKs activity (81 Ϯ 11 pmol/min⅐mg protein; P Ͻ 0.05) and phosphorylation significantly increased (P Ͻ 0.01). MEK activity was significantly increased by hyperglycemia (1251 Ϯ 136 vs. 2000 Ϯ 42 cpm; P ϭ 0.0017), whereas no changes were observed in MKP-1 expression. We conclude that hyperglycemia acutely stimulates ERKs activity and phosphorylation in human monocytes by the MEK pathway in vivo. These findings may be relevant in understanding the negative role of acute hyperglycemia on monocyte pathophysiology. (J Clin Endocrinol
doi:10.1210/jcem.86.3.7308 pmid:11238524 fatcat:nekey6fxendcva3vg73rqwyn64