Akt/PKB regulates numerous processes in the mammalian cell, including cell survival and proliferation, and glucose uptake in response to insulin. Abnormalities in Akt signalling are linked to the development of Type 2 diabetes, cardio-vascular disease, and cancer.

In the absence of insulin, Akt is predominantly found in the inactive state in the cytosol. Following insulin stimulation, Akt translocates to the plasma membrane, docks, and is phosphorylated to take on the active conformation. In turn, the activated Akt travels to and phosphorylates its many downstream substrates. Although crucial to the activation process, the translocation of Akt from the cytosol to the plasma membrane is currently not well understood.

Here we detail the parameter optimisation of a mathematical model of Akt translocation to experimental data. We have quantified the time delay between the application of insulin and the downstream Akt translocation response, indicating the constraints on the timing of the intermediate processes. A delay of approximately $0.4$ min prior to the Akt response was determined for the application of 1 nM insulin to cells in the basal state, whereas it was found that a further transition from physiological insulin to higher stimuli did not incur a delay.

Furthermore, our investigation indicates that the dominant processes regulating the appearance of Akt at the plasma membrane differ with the insulin level. For physiological insulin, the rate limiting step was the release of Akt to the plasma membrane in response to the insulin signal. In contrast, at high insulin levels, regulation of the recycling of Akt from the plasma membrane to the cytosol was also required.

Akt / PKB调节哺乳动物细胞中的许多过程，包括细胞存活和增殖以及响应胰岛素的葡萄糖摄取。Akt信号传导异常与2型糖尿病，心血管疾病和癌症的发生有关。

在没有胰岛素的情况下，Akt主要在细胞质中处于非活性状态。胰岛素刺激后，Akt易位至质膜，停靠并被磷酸化以呈现活性构象。继而，活化的Akt到达其许多下游底物并使之磷酸化。尽管对激活过程至关重要，但目前尚不清楚Akt从胞质溶胶向质膜的转运。

在这里，我们详细介绍了Akt易位到实验数据的数学模型的参数优化。我们已经量化了胰岛素的应用和下游Akt易位反应之间的时间延迟，表明了中间过程的时间限制。大约延迟$0.4$ 对于在基础状态下的细胞中应用1 nM胰岛素，确定在Akt响应之前的1分钟内，而发现从生理胰岛素到更高刺激的进一步过渡不会引起延迟。

此外，我们的研究表明，调节质膜Akt出现的主要过程随胰岛素水平的不同而不同。对于生理胰岛素，限速步骤是响应胰岛素信号将Akt释放至质膜。相反，在高胰岛素水平下，还需要调节Akt从质膜到细胞质的再循环。