Multiple chromatin-bound protein kinases assemble factors that regulate insulin gene transcription

Michael C. Lawrence, Chunli Shao, Kathleen McGlynn, Bashoo Naziruddin, Marlon F. Levy, Melanie H. Cobb

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 languageEnglish (US)
Pages (from-to)22181-22186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - Dec 19 2009


  • ERK1/2
  • Histone acetylation
  • Interleukin 1-β

ASJC Scopus subject areas

  • General


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