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Updated: Jun 12, 2026
07:09
Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States
Published on: April 1, 2015
Structural basis of insulin fibrillation.
Liwei Wang1, Catherine E Hall2, Emiko Uchikawa1
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science Advances
|September 15, 2023
Summary
Insulin fibrillation, a challenge in diabetes treatment, was studied using cryo-EM. Researchers designed less-fibrillating insulin mutants that retain therapeutic activity.
Area of Science:
- Biochemistry
- Structural Biology
- Diabetes Therapeutics
Background:
- Insulin is a critical hormone for glucose regulation and diabetes treatment.
- Insulin fibrillation into cross-β fibers complicates its storage and therapeutic use.
- The molecular mechanisms of insulin fibrillation are not fully understood.
Purpose of the Study:
- To characterize the structural basis of insulin fibrillation.
- To understand the molecular interactions driving fibril formation.
- To design insulin analogs with reduced fibrillation propensity.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine the structure of insulin fibrils.
- Multiple fibril forms containing protofilaments were identified.
- The high-resolution structure of a two-protofilament fibril was solved.
Main Results:
- Cryo-EM revealed multiple insulin fibril polymorphs composed of protofilaments.
- The 3.2-Å cryo-EM structure elucidated the β sheet conformation and inter-protofilament packing.
- Designed insulin mutants showed decreased fibrillation while preserving insulin receptor (IR) signaling.
Conclusions:
- The study provides a molecular understanding of insulin fibrillation.
- The determined structure facilitates the rational design of improved insulin formulations.
- Engineered insulin analogs hold promise for enhanced type 1 diabetes therapy.
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