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A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery.

ABSTRACT: 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.

SUBMITTER: Wang J

PROVIDER: S-EPMC7148115 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery.

Wang Jinqiang J Wang Zejun Z Yu Jicheng J Zhang Yuqi Y Zeng Yi Y Gu Zhen Z

Biomaterials science 20191014 11

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 ...[more]

PMID: 31608343

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