Effects of DHMEQ, a novel nuclear factor-kappab inhibitor, on beta cell dysfunction in INS-1 cells.

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.