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Multiple chromatin-bound protein kinases assemble factors that regulate insulin gene transcription
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 106(52)
- Publication Year :
- 2009
-
Abstract
- During the onset of diabetes, pancreatic beta cells become unable to produce sufficient insulin to maintain blood glucose within the normal range. Proinflammatory cytokines have been implicated in impaired beta cell function. To understand more about the molecular events that reduce insulin gene transcription, we examined the effects of hyperglycemia alone and together with the proinflammatory cytokine interleukin-1beta (IL-1beta) on signal transduction pathways that regulate insulin gene transcription. Exposure to IL-1beta in fasting glucose activated multiple protein kinases that associate with the insulin gene promoter and transiently increased insulin gene transcription in beta cells. In contrast, cells exposed to hyperglycemic conditions were sensitized to the inhibitory actions of IL-1beta. Under these conditions, IL-1beta caused the association of the same protein kinases, but a different combination of transcription factors with the insulin gene promoter and began to reduce transcription within 2 h; stimulatory factors were lost, RNA polymerase II was lost, and inhibitory factors were bound to the promoter in a kinase-dependent manner.
- Subjects :
- Models, Anatomic
Transcription, Genetic
Interleukin-1beta
E-box
In Vitro Techniques
Cell Line
Histones
Mice
Insulin receptor substrate
Insulin-Secreting Cells
Animals
Humans
Insulin
RNA, Messenger
Protein Precursors
Promoter Regions, Genetic
Transcription factor
STAT6
Multidisciplinary
Binding Sites
biology
General transcription factor
Base Sequence
GRB10
Acetylation
Fasting
Biological Sciences
Molecular biology
IRS2
Chromatin
Cell biology
Insulin receptor
Glucose
Hyperglycemia
biology.protein
Protein Kinases
Signal Transduction
Subjects
Details
- ISSN :
- 10916490
- Volume :
- 106
- Issue :
- 52
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....b6024421a0e166534ab15cad3804b7a1