Abstract
During the onset of diabetes, pancreatic β cells become unable to produce sufficient insulin to maintain blood glucose within the normal range. Proinflammatory cytokines have been implicated in impaired β 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-1β (IL-1β) on signal transduction pathways that regulate insulin gene transcription. Exposure to IL-1β in fasting glucose activated multiple protein kinases that associate with the insulin gene promoter and transiently increased insulin gene transcription in β cells. In contrast, cells exposed to hyperglycemic conditions were sensitized to the inhibitory actions of IL-1β. Under these conditions, IL-1β 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.
Original language | English (US) |
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Pages (from-to) | 22181-22186 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 106 |
Issue number | 52 |
DOIs | |
State | Published - Dec 19 2009 |
Keywords
- ERK1/2
- Histone acetylation
- Interleukin 1-β
ASJC Scopus subject areas
- General