Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 146, Issue 1, Pages 60-67Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjp.0706293
Keywords
thrombin; insulin; vascular smooth muscle cells; Src; p38 MAPK; glucose uptake
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1 Thrombin is a mitogen for vascular smooth muscle cells (VSMC) and has been implicated in the development in atherosclerosis. However, little is known about the role of thrombin in glucose transport in VSMC. 2 In this study, we examined the effect of thrombin on glucose uptake in rat A10 VSMC. We found that thrombin induced glucose uptake in a dose-dependent manner while hirudin, a potent thrombin inhibitor, prevented glucose uptake in the cells. PP2, a selective inhibitor of Src, prevented the thrombin-induced glucose uptake, but did not affect insulin-induced uptake. 3 We also examined whether mitogen-activated protein kinase (MAPK) inhibitors influenced thrombin-induced glucose uptake. The p38 MAPK inhibitor (SB203580) inhibited thrombin-induced glucose uptake, but the MEK inhibitor (PD98059) did not. In contrast to thrombin, SB203580 did not affect insulin-induced glucose uptake. Furthermore, thrombin failed to translocate the insulin-sensitive glucose transporter GLUT4. 4 These findings suggest that thrombin stimulates glucose transport via Src and subsequent p38 MAPK activation in VSMC.
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