- Sleep deprivation and its impact on circadian rhythms and glucose metabolism
- Award date
- 6 July 2016
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
The mammalian master pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN generates rhythms of behavioural and metabolic processes throughout the body via both endocrine and neuronal outputs. For example, daily rhythms of sleep-wake, fasting-feeding, plasma glucose, glucose tolerance and insulin sensitivity are regulated by SCN coordination of peripheral organs. Endogenous SCN rhythmicity is generated by a set of 10-15 clock genes generating oscillations of gene expression, making up an auto-regulatory feedback loop of ~24 hours (i.e., a circadian period). Light is the primary synchronizer of the SCN pacemaker though many light-independent factors such as behavioural arousal and metabolic cues also have phase and period resetting properties. The aim of this thesis was to study different aspects of the interactions between behavioural arousal, circadian rhythms and glucose metabolism. In the first part, we extended the study of brain control of glucose metabolism by investigating the central action of gastrin-releasing peptide (GRP), a neuropeptide synthesized in the SCN, on glucose metabolism in the rat. Our results indicate that central GRP induces long-lasting hyperglycemia. In the next chapter we showed that acute sleep deprivation in rats leads to impaired glucose tolerance. In the second part of the thesis, we demonstrated that behavioural arousal induced by sleep deprivation or caffeine treatment enhances photic-entrainment of the SCN clock in the diurnal Sudanian grass rat, Arvicanthis ansorgei. These circadian responses in a diurnal species are opposite to the earlier findings in nocturnal rodents and may have important biomedical applications for translational research.
- This PhD research project has been conducted as part of a cotutelle agreement between University of Strasbourg and University
Research conducted at: Netherlands Institute of Neurology NIN, University Strassbourg
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