Bar R S, Boes M, Sandra A
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa 52240.
J Clin Invest. 1988 Apr;81(4):1225-33. doi: 10.1172/JCI113439.
Using intact, beating hearts, we have assessed the interaction of insulin with capillary endothelium and the subsequent appearance of insulin in cardiac muscle. Rat hearts were perfused with 125I-insulin (10(-10) M) alone or in combination with unlabeled insulin (10(-9)-10(-5) M). 125I grains (shown to represent greater than 90% intact insulin) over both capillary endothelium and cardiac muscle decreased in a dose-dependent manner when hearts were co-perfused with labeled insulin and increasing concentrations of unlabeled insulin. Perfusion of 125I-desoctapeptide (DOP) insulin, a low affinity insulin analogue, with unlabeled insulin (10(-9)-10(-5) M) had no effect on the appearance of 125I-DOP insulin over microvessel endothelium and muscle. When capillary receptors were first destroyed by trypsin treatment or blocked by anti-receptor antibodies, the appearance of 125I-insulin in cardiac muscle decreased proportional to the inhibition of insulin binding to the capillary receptors. We conclude that insulin binding to capillary endothelial receptors is a central step in the transport of intravascular insulin to rat cardiac muscle.
我们使用完整的、跳动的心脏，评估了胰岛素与毛细血管内皮的相互作用以及随后胰岛素在心肌中的出现情况。用单独的125I-胰岛素（10^(-10) M）或与未标记的胰岛素（10^(-9)-10^(-5) M）联合灌注大鼠心脏。当心脏与标记胰岛素和浓度不断增加的未标记胰岛素共同灌注时，毛细血管内皮和心肌上的125I颗粒（显示代表超过90%的完整胰岛素）以剂量依赖的方式减少。用低亲和力胰岛素类似物125I-去八肽（DOP）胰岛素与未标记胰岛素（10^(-9)-10^(-5) M）灌注，对微血管内皮和肌肉上125I-DOP胰岛素的出现没有影响。当毛细血管受体首先被胰蛋白酶处理破坏或被抗受体抗体阻断时，心肌中125I-胰岛素的出现与胰岛素与毛细血管受体结合的抑制成比例地减少。我们得出结论，胰岛素与毛细血管内皮受体的结合是血管内胰岛素转运至大鼠心肌的核心步骤。
