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


CONCLUSIONS
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.
Saisho
Yoshifumi
Y
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hirose
Hiroshi
H
Horimai
Chihiro
C
Miyashita
Kiichi
K
Takei
Izumi
I
Umezawa
Kazuo
K
Itoh
Hiroshi
H
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003512:Cyclohexanones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D007340:Insulinoma / Q000473:pathology / Q000503:physiopathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001549:Benzamides; D003512:Cyclohexanones; D007328:Insulin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C464444:dehydroxymethylepoxyquinomicin; D005947:Glucose