Extracellular signal-regulated kinase is essential for interleukin-1-induced and nuclear factor kappaB-mediated gene expression in insulin-producing INS-1E cells

TY - JOUR

T1 - Extracellular signal-regulated kinase is essential for interleukin-1-induced and nuclear factor kappaB-mediated gene expression in insulin-producing INS-1E cells

AU - Larsen, Lykke

AU - Størling, J

AU - Darville, M

AU - Eizirik, D L

AU - Bonny, C

AU - Billestrup, N

AU - Mandrup-Poulsen, Thomas

PY - 2005/12/1

Y1 - 2005/12/1

N2 - The beta cell destruction and insulin deficiency that characterises type 1 diabetes mellitus is partially mediated by cytokines, such as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways are required for expression of the gene encoding inducible nitric oxide synthase (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by which these two pathways regulate beta cell Nos2 expression are currently unknown. Therefore, the aim of this study was to clarify the putative crosstalk between MAPK and NFkappaB activation in beta cells.

AB - The beta cell destruction and insulin deficiency that characterises type 1 diabetes mellitus is partially mediated by cytokines, such as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways are required for expression of the gene encoding inducible nitric oxide synthase (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by which these two pathways regulate beta cell Nos2 expression are currently unknown. Therefore, the aim of this study was to clarify the putative crosstalk between MAPK and NFkappaB activation in beta cells.

KW - Animals

KW - Apoptosis

KW - Blotting, Western

KW - Cell Line, Tumor

KW - Extracellular Signal-Regulated MAP Kinases

KW - Flavonoids

KW - Gene Expression

KW - Humans

KW - Imidazoles

KW - Insulin

KW - Insulin-Secreting Cells

KW - Interleukin-1

KW - MAP Kinase Kinase 4

KW - Mitogen-Activated Protein Kinase Kinases

KW - NF-kappa B

KW - Nitric Oxide Synthase Type II

KW - Phosphorylation

KW - Pyridines

KW - Rats

KW - Serine

KW - Synaptotagmin I

KW - p38 Mitogen-Activated Protein Kinases

U2 - 10.1007/s00125-005-0039-9

DO - 10.1007/s00125-005-0039-9

M3 - Journal article

C2 - 16283237

SN - 0012-186X

VL - 48

SP - 2582

EP - 2590

JO - Diabetologia

JF - Diabetologia

IS - 12

ER -