Insulin has been available for the treatment of diabetes for almost a century, and the variety of insulin choices today represents many years of discovery and innovation. Insulin has gone from poorly defined extracts of animal pancreata to pure and precisely controlled formulations that can be prescribed and administered with high accuracy and predictability of action. Modifications of the insulin formulation and of the insulin molecule itself have made it possible to approximate the natural endogenous insulin response. Insulin and insulin formulations had to be designed to produce either a constant low basal level of insulin or the spikes of insulin released in response to meals. We discuss how the biochemical properties of endogenous insulin were exploited to either shorten or extend the time-action profiles of injectable insulins by varying the pharmacokinetics (time for appearance of insulin in the blood after injection) and pharmacodynamics (time-dependent changes in blood sugar after injection). This has resulted in rapid-acting, short-acting, intermediate-acting, and long-acting insulins, as well as mixtures and concentrated formulations. An understanding of how various insulins and formulations were designed to solve the challenges of insulin replacement will assist clinicians in meeting the needs of their individual patients.

中文翻译：

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胰岛素的演变及其如何影响治疗和治疗选择。

近一个世纪以来，胰岛素一直可用于治疗糖尿病，如今胰岛素选择的多样性代表了多年的发现和创新。胰岛素已经从定义不明确的动物胰腺提取物转变为纯的、精确控制的制剂，可以以高精度和可预测的作用进行处方和给药。胰岛素制剂和胰岛素分子本身的改进使得接近天然内源性胰岛素反应成为可能。胰岛素和胰岛素配方必须设计为产生恒定的低基础胰岛素水平或响应进餐而释放的胰岛素峰值。我们讨论了如何通过改变药代动力学（注射后血液中胰岛素出现的时间）和药效学（血糖的时间依赖性变化）来利用内源性胰岛素的生化特性来缩短或延长注射胰岛素的时间作用曲线注射后）。这产生了速效、短效、中效和长效胰岛素，以及混合物和浓缩制剂。了解如何设计各种胰岛素和配方以解决胰岛素替代的挑战，将有助于临床医生满足个体患者的需求。短效、中效和长效胰岛素，以及混合物和浓缩制剂。了解如何设计各种胰岛素和配方以解决胰岛素替代的挑战，将有助于临床医生满足个体患者的需求。短效、中效和长效胰岛素，以及混合物和浓缩制剂。了解如何设计各种胰岛素和配方以解决胰岛素替代的挑战，将有助于临床医生满足个体患者的需求。