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Updated: Jul 6, 2026

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Effects of DHMEQ, a novel nuclear factor-kappab inhibitor, on beta cell dysfunction in INS-1 cells
Yoshifumi Saisho1, Hiroshi Hirose, Chihiro Horimai
1Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Aims:
Recent studies suggest that nuclear factor-kappaB (NF-kappaB) activation has an important role in leading to beta cell dysfunction in both type 1 and type 2 diabetes. In this study we tested this hypothesis by investigating the effects of dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kappaB inhibitor, on tumor necrosis factor-alpha (TNF-alpha)-induced beta cell dysfunction.
Methods:
INS-1 cells were incubated with TNF- alpha and with or without DHMEQ for 24 hours. Glucose-stimulated insulin secretion, cell viability, mRNA expression and NF-kappaB activation were investigated.
Results:
DHMEQ suppressed TNF-alpha-induced NF-kappaB activation and partially ameliorated glucose-stimulated insulin secretion in a dose-dependent manner. DHMEQ also partially ameliorated decreased cell viability and insulin mRNA level induced by TNF-alpha.
Conclusion:
DHMEQ suppressed NF-kappaB activation and ameliorated beta cell dysfunction induced by TNF- alpha. Inhibition of activated NF-kappaB in beta cells may be important to ameliorate beta cell dysfunction in diabetes.
Insights
Dehydroxymethylepoxyquinomicin (DHMEQ) reduces nuclear factor-kappaB (NF-kappaB) activation and improves beta cell function in diabetes models. This suggests inhibiting NF-kappaB may treat diabetes by protecting pancreatic beta cells.
Area of Science:
- Endocrinology
- Molecular Biology
- Diabetes Research
Background:
- Nuclear factor-kappaB (NF-kappaB) activation is implicated in beta cell dysfunction in both type 1 and type 2 diabetes.
- Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory cytokine contributing to beta cell damage.
Purpose of the Study:
- To investigate the therapeutic potential of dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kappaB inhibitor.
- To evaluate the effects of DHMEQ on TNF-alpha-induced beta cell dysfunction.
Main Methods:
- INS-1 cells were treated with TNF-alpha and varying concentrations of DHMEQ.
- Assessed glucose-stimulated insulin secretion, cell viability, mRNA expression, and NF-kappaB activation.
Main Results:
- DHMEQ significantly suppressed TNF-alpha-induced NF-kappaB activation in a dose-dependent manner.
- DHMEQ partially ameliorated TNF-alpha-induced reduction in glucose-stimulated insulin secretion and cell viability.
- DHMEQ also partially restored insulin mRNA levels affected by TNF-alpha.
Conclusions:
- DHMEQ effectively inhibits NF-kappaB activation and mitigates TNF-alpha-induced beta cell dysfunction.
- Targeting NF-kappaB in pancreatic beta cells represents a promising therapeutic strategy for managing diabetes.
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