Circadian clocks have profound effects on metabolism and behaviour , in plants and mammals.
In 1972, a study demonstrated that within the brain hypothalamus, the suprachiasmatic nucleus, which is close to the optic nerves, is required for daily rhythms in animal behaviour.. The suprachias¬matic nucleus receives light signals through the optic nerves, and so uses daylight cues to set the clock time and to couple light-dark transi¬tions to behavioural outputs.
Subsequent genetic studies identified several genes that mediate rhythmic behaviour.
The mammalian circadian clock is a molecular oscillator based on a nega¬tive- feedback loop in which the transcription factors CLOCK (or the related protein NPAS2) and BMALl work together to drive the expres¬sion of many genes, including the period (PERl, PER2 and PER3) and the cryptochrome (CRYl and CRY2) proteins.
Now it is clear that clocks outside the suprachiasrnatic nucleus have physiological roles?
First, expression of enzymes, transporters and receptors that regulate metabolism fluctuate robustly throughout the day.
Second circadian clocks outside the suprachiasmatic nucleus are adjusted on the basis of feeding time rather than the light-dark schedule For example, the cellular energy sensor AMPK controls the stability of cryptochromes and may contribute to nutrient entrainment of the clock in the liver.
Marcheva et al. have shown that the mouse pan¬creas also has a functional circadian clock, with individual pancreatic islets having clock function even when outside their normal tissue environment. The islet clock seems to consist of the same components as other mammalian circadian clocks, and drives rhythmic expression of genes involved in insulin sensing, glucose sensing, and islet growth and development. These clocks are therefore crucial for the specific metabolic needs and functions of islet cells .
Lamia and Evans 2010 Tick, tock , a β-cell clock Nature vol 466, 571-2
Marcheva et al 2010 Disruption of the clock components CLOCK and BMAL1 leads to hyper- insulinaemia and diabetes Nature vol 466 627-631
- Martin Eastwood