Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Diabetes Metab J. 2011 Jun;35(3):243-7. doi: 10.4093/dmj.2011.35.3.243. Epub 2011 Jun 30.
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.
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.
After treatment of 10(-7)M 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.
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.
胰岛素靶组织间质中的葡萄糖摄取与间质胰岛素浓度相关，而非与血浆胰岛素浓度相关。因此，胰岛素向靶组织间质的输送非常重要，内皮细胞也可能在胰岛素抵抗的发展中发挥重要作用。
用血管紧张素 II（ATII）处理牛主动脉内皮细胞后，观察胰岛素结合能力以及细胞膜和细胞质中胰岛素受体（IR）的变化。
用 10(-7)M ATII 处理后，胰岛素结合逐渐减少，60 分钟时减少至 60%（P<0.05）。ATII 受体阻滞剂（依普罗沙坦）呈剂量依赖性改善 ATII 降低的胰岛素结合能力（P<0.05）。200µM 时，依普罗沙坦完全恢复了胰岛素结合能力，尽管在治疗浓度下仅恢复了 20%至 30%。ATII 不影响 IR 的总量，但减少了质膜上的 IR 量并增加了细胞质中的 IR 量。
ATII 降低了测试细胞的胰岛素结合能力。ATII 不影响 IR 的总量，但减少了质膜上的 IR 量。我们的数据表明，ATII 通过将 IR 从质膜转位到细胞质来降低胰岛素的结合能力。胰岛素与 IR 的结合对于胰岛素诱导的血管舒张和跨内皮胰岛素转运很重要。因此，ATII 可能通过这种基于内皮的机制引起胰岛素抵抗。
