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Updated: Aug 5, 2026
15:04
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
FAIM Inhibits Insulin Amyloidogenesis through a Noncanonical Aggregation Pathway
Dana Wolfe1,2, Jhinuk Saha1,2, Joshua Mitchell3
1National High Magnetic Field Laboratory, 1800 E. Paul Dirac Drive, Tallahassee, FL 32310, United States.
Biorxiv : the Preprint Server for Biology
|July 29, 2026
Summary
Fas apoptosis inhibitory molecule (FAIM) prevents insulin amyloid formation, reducing its toxicity. This discovery offers insights into endogenous mechanisms protecting against insulin aggregation and related metabolic diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Disease Research
Background:
- Insulin misfolding into amyloid fibrils contributes to therapy complications and pancreatic beta-cell stress.
- Endogenous mechanisms preventing insulin aggregation are poorly understood, limiting therapeutic strategies.
Purpose of the Study:
- To identify endogenous suppressors of insulin amyloid formation.
- To elucidate the role of Fas apoptosis inhibitory molecule (FAIM) in regulating insulin aggregation and cytotoxicity.
Main Methods:
- Biochemical assays to assess beta-sheet formation and insulin assembly.
- In vitro studies to evaluate the cytotoxicity of insulin aggregates.
- Structural modeling to investigate FAIM-insulin interactions.
Main Results:
- Fas apoptosis inhibitory molecule (FAIM) was identified as an endogenous suppressor of insulin amyloid formation.
- FAIM reduces beta-sheet content in insulin and promotes disordered aggregates.
- FAIM attenuates the in vitro cytotoxicity of insulin aggregates, likely by masking aggregation-prone regions.
Conclusions:
- FAIM possesses anti-aggregation properties against insulin, extending its known functions.
- FAIM represents a potential endogenous mechanism for suppressing insulin amyloid formation.
- FAIM is highlighted as a candidate therapeutic target for modulating proteostasis in metabolic diseases.
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