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Updated: Oct 22, 2026

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
Published on: June 25, 2017
Small-molecule modulation of VDAC enhances glucose-stimulated insulin secretion by promoting ATP flux
Kohichi Matsunaga1, Kaori Honda2, Muneeb Ali3
1Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, 3-39-15, Showa-machi, Maebashi-shi, Gunma 371-8512, Japan; Laboratory of Molecular Endocrinology and Metabolism, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, 3-39-15, Showa-machi, Maebashi-shi, Gunma 371-8512, Japan.
Abstract:
Reduced insulin secretion by β cells is a pivotal factor in diabetes onset and progression. The small molecule NPD976 was identified as a potent insulin secretagogue using high-throughput chemical screening employing an insulin secretion assay system. Even part of the molecular structure of NPD976, designated as DPEU (N-[2-(3,4-dimethoxyphenyl)ethyl]urea), retains insulin secretagogue activity. DPEU enhances insulin secretion specifically under glucose stimulation in β cells derived from mice, rats, and humans. The compound localizes to mitochondria in a manner independent of high glucose stimulation. Biochemical analyses revealed that DPEU directly interacts with voltage-dependent anion channels (VDACs) located in the mitochondrial outer membrane, enhancing ATP efflux from mitochondria into the cytosol during glucose stimulation. To our knowledge, DPEU is a positive small-molecule modulator of VDAC function that promotes ATP flux in β cells through a mechanism distinct from the classical KATP or cAMP pathways. These findings identify VDAC as a potential target for enhancing insulin secretion.
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