Korean Diabetes Journal 1999;23(2):131-141.
Published online January 1, 2001.
Effect of Hyperglycemia on Internalization of Insulin-receptor Complexes in Human Umbilical Vein Endothelial Cells.
Ki Ho Song, Yu Bae Ahn, Je Ho Han, Soon Jip Yoo, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Department of Internal Medicine, College of Medicine, The Catholic University of Korea.
It is well known that hyperglycemia activates protein kinase C (PKC) in vascular endothelial cells. However, the effect of hyperglycemia on internalization and recycling of insulin receptors by insulin in endothelial cells has not been examined thus far. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated from healthy, pregnant women. Confluent HUVECs were incubated in a culture media containing either 5 (NG group) or 25 mM glucose (HG group) for 4 days. Then, we measured the insulin binding, internalization and recycling of the insulin receptor and release of internalized insulin into the media. RESULTS: There was no difference in binding of 0.17 nM 125I-insulin between the two groups. However, the amount of internalized 125I-insulin, determined by the aeid washing method, was significantly greater in the HG group compared to the NG group. The addition of 10 pM 1-(5-isoquino-linesulfonyl)-2-methyl-piperazine (H7), a PKC inhibitor, to the HG group prevented the increase of internalization in 125I-insulin. In addition, preincubation with unlabeled insulin resulted in a decrease of 125I-insulin binding to a greater extent in the HG group compared with the NG group, indicating that high glucose levels increased internalizntion of insulin receptors. The high glucose-induced increase in internalization of insulin receptors was prevented by an addition of H7. Recycling of insulin receptors to the cell surface was not affected by high glucose. Internalized 125I-insulin released into media with time. The released amount of I-insulin in the HC group tended to be greater compared to the NG group. CONCLUSION: These results suggest that hyperglycemia may increase internalization of the insulin-receptor complexes in vascular endothelial cells through PKC activation.
Key Words: Hyperglycemia, Protein kinase C, Insulin, Insulin receptor, Endothelial cell

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