Dual self-regulated delivery of insulin and glucagon by a hybrid patch
Dual self-regulated delivery of insulin and glucagon by a hybrid patch
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DOI：
10.1073/pnas.2011099117
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发表时间：
2020-11-24
影响因子：
11.1
通讯作者：
Gu, Zhen
中科院分区：
文献类型：
--
作者：
Wang, Zejun;Wang, Jinqiang;Gu, Zhen
β细胞功能降低和胰岛素缺乏是糖尿病的标志，糖尿病通常伴随着胰高血糖素分泌α细胞的功能障碍。虽然已经开发了胰岛素疗法来治疗胰岛素缺乏症，但用于急性低血糖症治疗的胰高血糖素的按需补充仍然不足。在这里，我们描述了一种透皮贴剂，其通过动态释放胰岛素或胰高血糖素来模拟用于血糖管理的β细胞和α细胞的固有反调节作用。这两个模块共享共聚基质，但包含不同比例的关键单体，对高血糖和低血糖状况都具有“双重响应”。在1型糖尿病小鼠模型中，混合贴剂有效地控制高血糖症，同时在模拟延迟进餐或胰岛素过量的胰岛素治疗环境中最小化低血糖症的发生。
Reduced beta-cell function and insulin deficiency are hallmarks of diabetes mellitus, which is often accompanied by the malfunction of glucagon-secreting alpha-cells. While insulin therapy has been developed to treat insulin deficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains inadequate. Here, we describe a transdermal patch that mimics the inherent counterregulatory effects of beta-cells and alpha-cells for blood glucose management by dynamically releasing insulin or glucagon. The two modules share a copolymerized matrix but comprise different ratios of the key monomers to be "dually responsive" to both hyperand hypoglycemic conditions. In a type 1 diabetic mouse model, the hybrid patch effectively controls hyperglycemia while minimizing the occurrence of hypoglycemia in the setting of insulin therapy with simulated delayed meal or insulin overdose.