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Updated: Jun 15, 2025

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
Published on: May 10, 2018
VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells
Gitanjali Roy1, Andrea Ordóñez1, Derk D Binns2
1Indiana Biosciences Research Institute, Indianapolis, IN, USA.
Dysfunctional beta cells in diabetes and hyperinsulinism may stem from hypersecretion. This study identifies VDAC1 and ER-associated degradation (ERAD) as key players in beta cell stress, offering potential therapeutic targets.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Medicine
Background:
- Beta cell dysfunction characterizes type 2 diabetes (T2D) and congenital hyperinsulinism (HI).
- Mechanisms linking beta cell hypersecretion to failure remain unclear.
Purpose of the Study:
- To investigate the molecular mechanisms underlying beta cell failure due to hypersecretion.
- To identify therapeutic targets for modulating beta cell function in T2D and HI.
Main Methods:
- Proteomics and functional assays in human and mouse beta cell lines.
- Time-course transcriptomics analysis.
- Immunostaining of human pancreatic tissue.
Main Results:
- VDAC1 identified as a target of the hypersecretion inducer SW016789, which enhances membrane depolarization and Ca2+ influx, leading to beta cell dysfunction.
- A distinct hypersecretory response signature was observed, highlighting ER-associated degradation (ERAD) as a key adaptive pathway.
- Altered distributions of ERAD components (SEL1L, HRD1, DERL3) were found in beta cells of T2D human pancreas.
Conclusions:
- SW016789 induces beta cell dysfunction via VDAC1 and ERAD pathways.
- ERAD is a critical adaptive response to hypersecretory stress in beta cells.
- VDAC1 and ERAD components represent potential therapeutic targets for treating beta cell dysfunction in metabolic diseases.
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