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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2275.)
© 2006 American Heart Association, Inc.

Vascular Biology

Repetitive Fluctuations in Blood Glucose Enhance Monocyte Adhesion to the Endothelium of Rat Thoracic Aorta

Kosuke Azuma; Ryuzo Kawamori; Yukiko Toyofuku; Yoshiro Kitahara; Fumihiko Sato; Tomoaki Shimizu; Kyoko Miura; Tomoyuki Mine; Yasushi Tanaka; Masako Mitsumata; Hirotaka Watada

From the Department of Medicine, Metabolism and Endocrinology (K.A., R.K., Y. Toyofuku, F.S., T.S., Y. Tanaka, H.W.), Juntendo University School of Medicine, Tokyo; Pharmaceutical Research Laboratories (Y.K., K.M., T.M.), Ajinomoto Co Inc, Kawasaki; and Department of Pathology (M.M.), Nihon University School of Medicine, Tokyo, Japan.

Correspondence to Hirotaka Watada, MD, PhD, Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail hwatada{at}med.juntendo.ac.jp

Background— The aim of this study was to elucidate the effect of repetitive fluctuations in blood glucose concentrations on monocyte adhesion to the aortic endothelium.

Methods and Results— Nonobese type 2 diabetes, Goto–Kakizaki (GK) rats were fed twice daily to induce repetitive postprandial glucose spikes. Then, we compared the number of monocytes adherent to the endothelium of thoracic aorta in these rats with that in rats fed ad libitum. To suppress the glucose spikes, rats were injected with an inhibitor of sodium–glucose transporter, phloridzin, just before each meal for 12 weeks. GK rats fed twice daily showed significantly lower HbA_1c than GK rats fed ad libitum. However, the former group showed markedly higher number of monocytes adherent to the endothelium than the latter, together with increased arterial intimal thickening. Phloridzin significantly reduced the number of adherent monocytes in GK rats fed twice daily.

Conclusion— Our data demonstrated that repetitive postprandial fluctuation in glucose concentration evokes monocyte adhesion to endothelial cells that was worse than that induced by stable hyperglycemia in vivo. Suppression of such fluctuations efficiently suppressed monocyte adhesion to the aortic endothelium.

We investigated the distinct role of fluctuations in blood glucose on monocyte adhesion to aortic endothelial cells. Our data demonstrated that repetitive postprandial fluctuation in glucose concentration evokes monocyte adhesion to endothelial cells that was worse than that induced by stable hyperglycemia. Suppression of such fluctuations efficiently suppressed monocyte adhesion.

Key Words: monocyte–endothelial interaction • postprandial hyperglycemia • cardiovascular disease • NEMOes • glucose spike

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