title: Suprachiasmatic Nucleus Neuropeptides and Their Control of Endogenous Glucose Production.
abstract: Defective control of endogenous glucose production is an important factor responsible for hyperglycaemia in the diabetic individual. During the past decade, progressively more evidence has appeared indicating a strong and potentially causal relationship between disturbances of the circadian system and defects of metabolic regulation, including glucose metabolism. The detrimental effects of disturbed circadian rhythms may have their origin in disturbances of the molecular clock mechanisms in peripheral organs, such as the pancreas and liver, or in the central brain clock in the hypothalamic suprachiasmatic nuclei (SCN). To assess the role of SCN output per se on glucose metabolism, we investigated (i) the effect of several SCN neurotransmitters on endogenous glucose production and (ii) the effect of SCN neuronal activity on hepatic and systemic insulin sensitivity. We show that silencing of SCN neuronal activity results in decreased hepatic insulin sensitivity and increased peripheral insulin sensitivity. Furthermore, both oxytocin neurones in the paraventricular nucleus of the hypothalamus (PVN) and orexin neurones in the lateral hypothalamus may be important targets for the SCN control of glucose metabolism. These data further highlight the role of the central clock in the pathophysiology of insulin resistance.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Foppen
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A A T
authors.initials: AA
authors.lastname: Tan
authors.affiliation: Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.|Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience (NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Kalsbeek
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000096:biosynthesis*; D007026:Hypothalamic Area, Lateral / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D000068797:Orexins / Q000502:physiology*; D010121:Oxytocin / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D009479:Neuropeptides; D000068797:Orexins; D010121:Oxytocin
keywords: circadian; glucose; insulin; oxytocin; paraventricular nucleus; vasopressin