A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery.
A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery.
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DOI：
10.1039/c9bm01283d
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发表时间：
2019-10
影响因子：
6.6
通讯作者：
Jinqiang Wang;Zejun Wang;Jicheng Yu;Yuqi Zhang;Yi Zeng;Zhen Gu
中科院分区：
文献类型：
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作者：
Jinqiang Wang;Zejun Wang;Jicheng Yu;Yuqi Zhang;Yi Zeng;Zhen Gu
用于糖尿病管理的胰岛素给药伴随着低血糖，预期可通过具有响应血糖水平（BGL）波动的自我调节能力的葡萄糖响应智能胰岛素缓解低血糖。在这里，我们已经制备了一种新的胰岛素类似物修饰胰岛素与毛喉素（指定为胰岛素-F），葡萄糖转运蛋白（Glut）抑制剂。在体外，胰岛素-F能够与红细胞血影上的Glut结合，可被葡萄糖和细胞松弛素B抑制。在1型糖尿病小鼠中皮下注射后，胰岛素-F可将BGL维持在200 mg mL-1以下长达10 h，连续两次注射可达到20 h。此外，胰岛素-F还与内源性Gluts结合。在葡萄糖激发后，升高的葡萄糖水平竞争性地取代并释放与Glut结合的胰岛素-F，使BGL迅速恢复至正常范围。
Insulin administration for the management of diabetes is accompanied by hypoglycemia, which is expected to be mitigated by glucose-responsive smart insulin that has self-regulation ability in response to blood glucose level (BGL) fluctuation. Here, we have prepared a new insulin analog by modifying insulin with forskolin (designated as insulin-F), a glucose-transporter (Glut) inhibitor. In vitro, insulin-F is capable of binding to Glut on erythrocyte ghosts, which can be inhibited by glucose and cytochalasin B. Upon subcutaneous injection in type 1 diabetic mice, insulin-F maintains BGLs below 200 mg mL-1 for up to 10 h, and achieves 20 h with two sequential injections. Moreover, insulin-F also binds to endogenous Gluts. Upon a glucose challenge, the elevated level of glucose competitively replaces and liberates insulin-F that binds to Glut, rapidly restoring BGLs to the normal range.