Disrupting key body clock proteins CLOCK and BMAL1 may cause low insulin levels and diabetes

Pancreatic islets exhibit circadian gene and protein oscillations of key transcription factors that may influence insulin secretion.

• The transcription factors CLOCK and BMAL1 display self-sustained circadian oscillations in pancreatic islets.
• In circadian mutant mice, the timing of oscillation for genes related to growth, glucose metabolism, and insulin signaling is delayed.
• Mutant mice lacking Clock and Bmal1 show impaired glucose tolerance and reduced insulin secretion, with worsening defects in islet size and proliferation as they age.
• Disruption of the Clock gene leads to widespread changes in the expression of islet genes linked to growth, survival, and vesicle assembly.
• Conditional removal of the pancreatic circadian clock can result in diabetes mellitus due to impaired beta-cell function.

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