Elevated ambient glucose induces acute inflammatory events in the microvasculature: effects of insulin

Gregory Booth, Timothy J. Stalker, Allan M. Lefer, Rosario Scalia
2001 American Journal of Physiology. Endocrinology and Metabolism  
Elevated ambient glucose induces acute inflammatory events in the microvasculature: effects of insulin. Am J Physiol Endocrinol Metab 280: E848-E856, 2001.-We employed intravital microscopy of the rat mesenteric microvasculature to study the effects of local hyperglycemia on leukocyte-endothelial cell interactions. Intraperitoneal injection of 6, 12.5, and 25 mmol/l D-glucose to the rat significantly and time-dependently increased leukocyte rolling and leukocyte adherence in, and leukocyte
more » ... and leukocyte transmigration through mesenteric venules compared with control rats injected with Krebs-Henseleit (K-H) solution alone or given 25 mmol/l L-glucose intraperitoneally. The response elicited by D-glucose was associated with significant attenuation of endothelial nitric oxide (NO) release, as demonstrated by direct measurement of NO release in inferior vena caval segments isolated from rats exposed to 25 mmol/l D-glucose for 4 h (P Ͻ 0.01 vs. vena caval segments from control rats). Local application of 0.05 U/min insulin for 90 min significantly attenuated glucose-induced leukocyte rolling, adherence, and migration (P Ͻ 0.01 from 25 mmol/l D-glucose alone). Immunohistochemical localization of P-selectin expressed on endothelial surface was significantly increased 4 h after exposure of the mesenteric tissue to high ambient glucose (P Ͻ 0.01 vs. ileal venules from rats injected with K-H solution alone or 25 mmol/l L-glucose). Insulin markedly inhibited endothelial cell surface expression of P-selectin in ileal venules exposed to elevated ambient glucose in vivo (P Ͻ 0.01 vs. control rats injected with 25 mmol/l L-glucose). These data demonstrate that acute increases in ambient glucose comparable to those seen in diabetic patients are able to initiate an inflammatory response within the microcirculation. This inflammatory response to glucose is associated with upregulation of the endothelial cell adhesion molecule P-selectin and can be blocked by local application of insulin. rat mesentery; diabetes; P-selectin THE VASCULAR ENDOTHELIUM is a structurally simple but functionally complex cell layer whose integrity is essential for normal vascular function (23). Several acute and chronic pathological conditions are associated with impaired endothelial cell function (i.e., endothelial dysfunction) (15, 42). Among these conditions, diabetes mellitus is of particular relevance because of its high
doi:10.1152/ajpendo.2001.280.6.e848 pmid:11350766 fatcat:qn64vbpzhneg3cuks3jsma5l4q