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Pancreatic β cell enhancers regulate rhythmic transcription of genes controlling insulin secretion.


ABSTRACT: The mammalian transcription factors CLOCK and BMAL1 are essential components of the molecular clock that coordinate behavior and metabolism with the solar cycle. Genetic or environmental perturbation of circadian cycles contributes to metabolic disorders including type 2 diabetes. To study the impact of the cell-autonomous clock on pancreatic β cell function, we examined pancreatic islets from mice with either intact or disrupted BMAL1 expression both throughout life and limited to adulthood. We found pronounced oscillation of insulin secretion that was synchronized with the expression of genes encoding secretory machinery and signaling factors that regulate insulin release. CLOCK/BMAL1 colocalized with the pancreatic transcription factor PDX1 within active enhancers distinct from those co

SUBMITTER: Perelis M 

PROVIDER: S-EPMC4669216 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature