Webber Matthew J, Anderson Daniel G, Langer Robert
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, MA 02115, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Department of Anesthesiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge MA 02139, USA; Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Expert Rev Endocrinol Metab. 2015;10(5):483-489. doi: 10.1586/17446651.2015.1071187. Epub 2015 Jul 18.
Though a suite of different insulin variants have been used clinically to provide greater control over pharmacokinetics, no clinically used insulin can tune its potency and/or bioavailability in a glucose-dependent manner. In order to improve therapy for diabetic patients, a vision has been the development of autonomous closed-loop approaches. Toward this goal, insulin has been synthetically modified with glucose-sensing groups or groups that can compete with free glucose for binding to glucose-binding proteins and evaluated in pre-clinical models. Specifically, it was demonstrated that site-specific modification of insulin with phenylboronic acid can result in glucose-responsive activity, leading to faster recovery in diabetic mice following a glucose challenge but with less observed hypoglycemia in healthy mice. This strategy, along with several others being pursued, holds promise to improve the fidelity in glycemic control with routine insulin therapy.
尽管一系列不同的胰岛素变体已在临床上用于更好地控制药代动力学，但目前临床上使用的任何胰岛素都无法以葡萄糖依赖的方式调节其效力和/或生物利用度。为了改善糖尿病患者的治疗，自主闭环方法的开发一直是一个愿景。为了实现这一目标，胰岛素已被用葡萄糖感应基团或能与游离葡萄糖竞争结合葡萄糖结合蛋白的基团进行合成修饰，并在临床前模型中进行了评估。具体而言，已证明用苯硼酸对胰岛素进行位点特异性修饰可产生葡萄糖反应活性，使糖尿病小鼠在葡萄糖激发后恢复得更快，但健康小鼠出现低血糖的情况较少。这一策略以及正在探索的其他几种策略，有望提高常规胰岛素治疗血糖控制的精准度。
