Daily Variations in Type II Iodothyronine Deiodinase Activity in the Rat Brain as Controlled by the Biological Clock

Kalsbeek, Andries; Buijs, Ruud M.; Schaik, R. van; Kaptein, Ellen; Visser, Theo J.; Zandieh-Doulabi, Behrouz; Fliers, Eric

doi:10.1210/en.2004-0763

Cited by 36 publications

(15 citation statements)

References 78 publications

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“…In Eu Int rats, biochemical euthyroidism was evidenced by TSH concentrations similar to those reported earlier (18,19) in control rats without hormonal treatment. Plasma TSH concentrations were between 2.00 and 3.00 mU/l in all euthyroid groups.…”

Section: Plasma Thyroid Hormonessupporting

confidence: 87%

Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats

Klieverik¹,

Sauerwein²,

Ackermans³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Klieverik LP, Sauerwein HP, Ackermans MT, Boelen A, Kalsbeek A, Fliers E. Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats. Am J Physiol Endocrinol Metab 294: E513-E520, 2008. First published January 8, 2008 doi:10.1152/ajpendo.00659.2007.-Thyrotoxicosis is known to induce a broad range of changes in carbohydrate metabolism. Recent studies have identified the sympathetic and parasympathetic nervous system as major regulators of hepatic glucose metabolism. The present study aimed to investigate the pathogenesis of altered endogenous glucose production (EGP) in rats with mild thyrotoxicosis. Rats were treated with methimazole in drinking water and L-thyroxine (T4) from osmotic minipumps to either reinstate euthyroidism or induce thyrotoxicosis. Euthyroid and thyrotoxic rats underwent either a sham operation, a selective hepatic sympathetic denervation (Sx), or a parasympathetic denervation (Px). After 10 days of T4 administration, all animals were submitted to a hyperinsulinemic euglycemic clamp combined with stable isotope dilution to measure EGP. Plasma triiodothyronine (T3) showed a fourfold increase in thyrotoxic compared with euthyroid animals. EGP was increased by 45% in thyrotoxic compared with euthyroid rats and correlated significantly with plasma T3. In thyrotoxic rats, hepatic PEPCK mRNA expression was increased 3.5-fold. Relative suppression of EGP during hyperinsulinemia was 34% less in thyrotoxic than in euthyroid rats, indicating hepatic insulin resistance. During thyrotoxicosis, Sx attenuated the increase in EGP, whereas Px resulted in increased plasma insulin with unaltered EGP compared with intact animals, compatible with a further decrease in hepatic insulin sensitivity. We conclude that chronic, mild thyrotoxicosis in rats increases EGP, whereas it decreases hepatic insulin sensitivity. Sympathetic hepatic innervation contributes only to a limited extent to increased EGP during thyrotoxicosis, whereas parasympathetic hepatic innervation may function to restrain EGP in this condition. thyroid hormone; autonomic nervous system; sympathetic; parasympathetic THYROTOXICOSIS IS ASSOCIATED WITH A BROAD RANGE of alterations in metabolism and energy homeostasis. Endogenous glucose production (EGP), lipolysis, and proteolysis are increased during thyrotoxicosis, providing the substrates needed for the concomitant increase in energy expenditure (12). Thyrotoxic patients exhibit increased EGP and hepatic insulin resistance, i.e., hampered suppressive action of insulin on EGP (6, 12). It is widely assumed that the metabolic alterations during thyrotoxicosis represent direct effects of thyroid hormone (TH) on the expression of TH-responsive genes, mediated by binding of triiodothyronine (T 3 ) to TH receptors in peripheral organs (39). Indeed, one of the main target organs for metabolic effects of TH is the liver, which has a key role in maintaining glucose homeostasis.Until quite recently, the role of the central nervous system (CNS) as a focus of...

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Section: Plasma Thyroid Hormonessupporting

confidence: 87%

Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats

Klieverik¹,

Sauerwein²,

Ackermans³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…As far as we know, this is the first demonstration of a diurnal rhythm of Dio2 expression in the MBH. This result is important to unravel the molecular basis driving the day-night rhythm in Dio2 activity and concentrations of T 3 and T 4 , which were reported in the hypothalamus of rats (29 -31) and shown to be driven by the suprachiasmatic nucleus (30). The comparison between animals maintained under long-and short-day conditions revealed that Dio2 mRNA levels were significantly higher in long-day conditions at ZT9 in the EC and at ZT9 and -15 in the TIS.…”

Section: Discussionmentioning

confidence: 73%

Temporal Dynamics of Type 2 Deiodinase Expression after Melatonin Injections in Syrian Hamsters

et al. 2007

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In many species living in temperate zones, reproduction is controlled by the photoperiod. Recent findings have clarified that type 2 iodothyronine deiodinase (Dio2) plays a significant role in the photoperiodic response of gonads in the mediobasal hypothalamus, converting the prohormone T(4) into bioactive T(3). In mammals, Dio2 expression is suppressed by long-term melatonin injections, although the signal transduction pathways that link the melatonin signal to Dio2 expression are unknown. As a first step to approach the problem, we have here investigated the temporal dynamics of the melatonin effect on Dio2 expression using male Syrian hamsters. Dio2 mRNA levels were found to show diurnal rhythms under long-day conditions in an area adjacent to the tuberoinfundibular sulcus and in the ependymal cell layer lining the ventrobasal walls of the third ventricle. Daily sc melatonin injections given in the late afternoon under long-day condition suppressed the Dio2 mRNA levels already at the first day after the onset of the treatment in the ependymal cell layer lining the ventrobasal walls of the third ventricle, and 1 d later in an area adjacent to the tuberoinfundibular sulcus. These suppressive effects were sustained for at least 2 d after a single injection. Furthermore, we examined the temporal changes of the Dio2 expression after the onset of the treatment, showing that the suppression did not occur until midday of the next day. These data suggest that melatonin is involved in the signal transduction mechanisms controlling the photoperiodic response of gonads by acting on Dio2 expression rather rapidly through indirect pathways.

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“…Although many details remain to be confirmed, a conservative interpretation of these results is that the thyronamines T1AM and T0AM are naturally occurring relatives of TH that might be generated by the concerted actions of aromatic acid decarboxylase and the three TH deiodinases that have been described (Visser et al, 1994;Kuiper et al, 2000;Kalsbeek et al, 2005;Köhrle, 2005;Moreno, et al, 2005). However, the possibility that alternative routes of thyronamine biosynthesis exist must also be explored.…”

Section: Thermoregulation and Metabolism-mentioning

confidence: 99%

Trace amine-associated receptor 1—Family archetype or iconoclast?

Grandy

2007

Pharmacology & Therapeutics

176

211

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Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the 'trace amines' (TAs) β-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of two publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers as TA1 (Borowsky et al., 2001) and TAR1 (Bunzow et al., 2001). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines recombinant rodent and human TA receptors dosedependently couple to the stimulation of cAMP production. Structure-activity profiling based on this functional response has revealed that in addition to the TAs, other biologically active compounds containing a 2 carbon aliphatic side chain linking an amino group to at least one benzene ring are potent and efficacious TA receptor agonists with amphetamine, methamphetamine, 3-iodothyronamine, thyronamine, and dopamine among the most notable. Almost 100 years after the search for TA receptors began numerous TA1/TAR1-related sequences, now called Trace AmineAssociated Receptors (TAARs), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TA receptor a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCRs. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.

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Daily Variations in Type II Iodothyronine Deiodinase Activity in the Rat Brain as Controlled by the Biological Clock

Cited by 36 publications

References 78 publications

Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats

Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats

Temporal Dynamics of Type 2 Deiodinase Expression after Melatonin Injections in Syrian Hamsters

Trace amine-associated receptor 1—Family archetype or iconoclast?

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