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KMID : 1200020110350030243
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Diabetes & Metabolism Journal
2011 Volume.35 No. 3 p.243 ~ p.247
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Angiotensin II Inhibits Insulin Binding to Endothelial Cells
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Oh Su-Jin
Ha Won-Chul
Lee Jee-In
Sohn Tae-Seo
Kim Ji-Hyun
Lee Jung-Min
Chang Sang-Ah
Hong Oak-Kee
Son Hyun-Shik
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Abstract
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Background: Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance.
Methods: After treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol.
Results: After treatment of 10-7M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05). ATII receptor blocker (eprosartan) dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05). At 200 μM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol.
Conclusion: ATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.
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KEYWORD
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Angiotensin II, Angiotensin II receptor blocker, Endothelium, Insulin resistance, Transcapillary insulin transport
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