The sympathetic system as an output of the central clock. It’s role in metabolic rhythms.
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1
Academic Medical Center (AMC) of the University of Amsterdam (UvA), Endocrinology and Metabolism, Netherlands
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2
Netherlands Institute for Neuroscience, Hypothalamic Integration Mechanisms, Netherlands
Accumulating evidence indicates an association between the development of obesity and type 2 diabetes at the one hand and disturbances in circadian control at the other hand. Disruption of circadian rhythms can be caused by external factors such as shift work and jet lag, but also by pathophysiologal factors including aging, depression and sleep disorders. It remains unclear, however, what the precise contribution of the suprachiasmatic nucleus (SCN), i.e., the central circadian pacemaker, is in the regulation of glucose and energy homeostasis.
The SCN uses its projections to neuro-endocrine and pre-autonomic neurons in the hypothalamus to control daily hormone rhythms, e.g. adrenal corticosterone, luteinizing hormone (LH) and pineal melatonin release. The SCN also plays an essential role in maintaining daily blood glucose concentrations. Indeed both glucose production and glucose uptake show a pronounced daily rhythm, with increased glucose uptake as well as glucose production at the time of awakening. Using local intra-hypothalamic administration of GABA and glutamate receptor (ant)agonists we previously demonstrated how changes in autonomic nervous system activity contribute to the daily control of plasma glucose and insulin concentrations. More recent studies evidenced an important role for VIP, but not vasopressin, as an SCN output in the control of hepatic glucose production. In addition, hypothalamic orexin and oxytocin neurons turned out to be important targets for the SCN to transmit its glucoregulatory effects onto the autonomic nervous system.
Finally, using localized bilateral infusions of the sodium channel blocker tetrodotoxin (TTX) in the rat SCN, to silence SCN neuronal activity, combined with euglycemic hyperinsulinemic clamp studies we found that an acute reduction of SCN output resulted in hepatic insulin resistance as well as increased peripheral glucose uptake. Together these results indicate that a withdrawal of SCN neuronal activity at the end of the light period increases activity of the orexin neurons which, in turn, results in an increased hepatic glucose production as well as an increased peripheral glucose tolerance.
Keywords:
Hypothalamus,
Autonomic Nervous System,
circadian rhythms,
Endocrinology,
Glucose,
vasopressin
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Kalsbeek
A
(2013). The sympathetic system as an output of the central clock. It’s role in metabolic rhythms.
.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00038
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Received:
28 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Prof. Andries Kalsbeek, Academic Medical Center (AMC) of the University of Amsterdam (UvA), Endocrinology and Metabolism, Amsterdam, Noord-Holland, 1105AZ, Netherlands, a.kalsbeek@amc.uva.nl