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Updated: Sep 4, 2025

An In Ovo Model for Testing Insulin-mimetic Compounds
Published on: April 23, 2018
Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide
Mengmeng Wang1,2,3,4, Jing-Xiang Wu1,4, Lei Chen1,2,3,4
1State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, College of Future Technology, Institute of Molecular Medicine, Peking University, Beijing, China.
Abstract:
Mitiglinide is a highly selective fast-acting anti-diabetic drug that induces insulin secretion by inhibiting pancreatic KATP channels. However, how mitiglinide binds KATP channels remains unknown. Here, we show the cryo-EM structure of the SUR1 subunit complexed with mitiglinide. The structure reveals that mitiglinide binds inside the common insulin secretagogue-binding site of SUR1, which is surrounded by TM7, TM8, TM16, and TM17. Mitiglinide locks SUR1 in the NBD-separated inward-facing conformation. The detailed structural analysis of the mitiglinide-binding site uncovers the molecular basis of its high selectivity.
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