Insulin detemir is a fully efficacious, low affinity agonist at the insulin receptor
Insulin detemir is a fully efficacious, low affinity agonist at the insulin receptor
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DOI：
10.1111/j.1463-1326.2010.01206.x
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发表时间：
2010-08-01
影响因子：
5.8
通讯作者：
Brand, C. L.
中科院分区：
文献类型：
--
作者：
Sorensen, A. R.;Stidsen, C. E.;Brand, C. L.
方法：测定在不同白蛋白浓度下，人、大鼠肝细胞和过表达人胰岛素受体（CHO-hIR）的中国仓鼠卵巢细胞中膜相关胰岛素受体的位移。随着时间的推移，大鼠脂肪细胞的脂肪生成以及同时存在地特胰岛素和人胰岛素或分离胰岛素的影响进行了评估。采用大鼠高胰岛素血症血糖钳夹技术建立了多个代谢终点的剂量-反应曲线，并研究了地特胰岛素和人胰岛素同时存在的影响。结果：与人用胰岛素相比，地特米胰岛素在体外和体内均表现出充分的疗效和右移的平行剂量-反应曲线。体内和体外以及不同体外条件下的效价估计值不同，即随着白蛋白浓度的增加，体外效价降低。地特米胰岛素与人胰岛素在体内体外均具有互补性。结论：与人胰岛素相比，地特尼胰岛素在体内和体外代谢终点均完全有效。效价估计依赖于方法，这一事实强调了在表征地特尼胰岛素时建立完全剂量-反应关系的重要性。
Methods: Displacement of membrane-associated insulin receptors from human and rat hepatocytes, and from Chinese Hamster Ovary cells over-expressing human insulin receptor (CHO-hIR) at varying albumin concentrations is measured. Lipogenesis in primary rat adipocytes over time and the effects in the simultaneous presence of insulin detemir and human insulin or insulin aspart are assessed. The hyperinsulinaemic euglycaemic clamp technique in rats is used to establish dose-response curves for multiple metabolic endpoints and to investigate the effects of the simultaneous presence of insulin detemir and human insulin.Results: Both in vitro and in vivo, insulin detemir shows full efficacy and right-shifted parallel dose-response curves compared with human insulin. The potency estimates are different between the in vivo and in vitro conditions and among different in vitro conditions, that is the potency decreases in vitro with increasing albumin concentration. The effects of insulin detemir and human insulin are additive both in vitro and in vivo.Conclusions: Insulin detemir is fully efficacious compared with human insulin on all metabolic endpoints measured in vitro and in vivo. The fact that the potency estimates are method-dependent emphasizes the importance of establishing full dose-response relationships when characterizing insulin detemir.