Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

Song, Zilong; Levin, Barry E.; Stevens, Wanida; Sladek, Celia D.

doi:10.1152/ajpregu.00520.2013

Cited by 52 publications

(52 citation statements)

References 88 publications

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“…The SON expresses insulin receptors and glucokinase, an enzyme considered to play a critical role in glucose-sensitive cells of the brain, pancreas and liver. In an in vitro model, glucose and insulin stimulated oxytocin release from explants containing the SON (35,36). However, in in vitro slice preparations, SON neurones do not increase their firing rate in response to increased glucose in the perifusion medium (30), and i.v.…”

Section: Discussionmentioning

confidence: 99%

High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

2017

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Oxytocin is a potent anorexigen and is believed to have a role in satiety signaling. We developed rat models to study the activity of oxytocin neurons in response to voluntary consumption or oral gavage of foods using c-Fos immunohistochemistry and in vivo electrophysiology. Using c-Fos expression as an indirect marker of neural activation, we showed that the percentage of magnocellular oxytocin neurons expressing c-Fos increased with voluntary consumption of sweetened condensed milk (SCM). To model the effect of food in the stomach, we gavaged anesthetized rats with SCM. The percentage of supraoptic nucleus and paraventricular nucleus magnocellular oxytocin-immunoreactive neurons expressing c-Fos increased with SCM gavage but not with gastric distention. To further examine the activity of the supraoptic nucleus, we made in vivo electrophysiological recordings from SON neurons, where anesthetized rats were gavaged with SCM or single cream. Pharmacologically identified oxytocin neurons responded to SCM gavage with a linear, proportional, and sustained increase in firing rate, but cream gavage resulted in a transient reduction in firing rate. Blood glucose increased after SCM gavage but not cream gavage. Plasma osmolarity and plasma sodium were unchanged throughout. We show that in response to high-sugar, but not high-fat, food in the stomach, there is an increase in the activity of oxytocin neurons. This does not appear to be a consequence of stomach distention or changes in osmotic pressure. Our data suggest that the presence of specific foods with different macronutrient profiles in the stomach differentially regulates the activity of oxytocin neurons.

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Section: Discussionmentioning

confidence: 99%

High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

2017

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“…In the present case, the patient showed increase of serum vasopressin level. Vasopressin is related in water intake regulation and its containing neuron is located in supraoptic nucleus and K ATP channel is considered to be involved in its secretory mechanism [25,26]. It is possible that modulation of K ATP channel activity by DEND syndrome mutation or sulfonylurea treatment may have affected vasopressin secretion and thereby affected water intake in our case.…”

Section: Discussionmentioning

confidence: 95%

Water intake disorder in a DEND syndrome afflicted patient with R50P mutation

et al. 2015

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The ATP-sensiTive K + (K ATP ) channel is a key factor that couples cell metabolisms with the changes in cell excitability in various tissues including pancreatic b-cells and the brain [1,2]. It is a hetero-octameric complex composed of four pore-forming Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits. In pancreatic β-cells, K ATP channels play a major role in regulating insulin secretion. A rise in plasma glucose stimulates glucose uptake and metabolism, causing an increase in intracellular ATP in β-cells. These changes in adenine nucleotide concentration result in the closure of the K ATP channel. The decrease in the membrane's K + permeability by closureWater intake disorder in a DEND syndrome afflicted patient with R50P mutation Abstract. In this study, we present a case of developmental delay, epilepsy and neonatal diabetes (DEND) syndrome in a young male patient with the R50P mutation located in the Kir6.2 subunit of the ATP-sensitive K + (K ATP ) channel. Whereas most patients with DEND syndrome are resistant to sulfonylurea therapy, our patient was responsive to sulfonylurea, lacked the most common neurological symptoms, such as epilepsy, but refused to drink water. His serum electrolytes and plasma osmolarity were normal but the serum vasopressin level was increased. To investigate the underlying mechanism of his water intake disorder, a 5 mL aliquot of 340 mM K ATP channel opener diazoxide or 100 mM K ATP channel inhibitor glibenclamide was injected into the third ventricle of the rat brain, and water intake was monitored. Although the injection of glibenclamide had no effect, injection of diazoxide significantly increased water intake by about 1.5 fold without affecting food intake. This result indicates that the K ATP channel activity in the brain may have an influence on water intake. Here, we present the first case of a DEND syndrome-afflicted patient with water intake disorder and increased serum vasopressin level, possibly related to altered K ATP channel activity. ] i , and this increase triggers the release of insulin [3].Mutations in KCNJ11, the gene encoding the Kir6.2 subunit, are known to cause neonatal diabetes. Some mutations are known to give rise to a severe form of disease, the DEND syndrome [3,4]. Aside from hyperglycaemia, DEND syndrome is characterized by severe neurological features such as developmental delay, epilepsy, and muscle weakness [5].The case we present in this paper was diagnosed with DEND syndrome at the age of 7 months due to the presence in his genome of a mutation of arginine to proline in residue 50 of Kir6.2 (R50P). Previously, we reported that the R50P mutation of Kir6.2 causes DEND syndrome [6]. A functional electrophysiological study on the K ATP channel with the R50P mutation

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“…SON is composed of magnocellular neurons that project to the posterior pituitary resulting in secretion of oxytocin into the periphery. Activity of SON oxytocin neurons is regulated by hypertonic solution [117], serotonin, noradrenalin [118], glucose [119], and α-MSH [120]. α-MSH inhibits the electrical activity of oxytocin neurons and inhibits secretion from its nerve ending but induces dendritic oxytocin release independently from its neuron activity [120].…”

Section: The Regulation Of Son Oxytocin Neuronsmentioning

confidence: 99%

“…In SON oxytocin neurons, it is considered that insulin activates phosphatidylinositol 3 kinase (PI3K), which induces the translocation of glucose transporter (GLUT) 4 into the membrane [119]. Although GLUT3 is already present in the SON neuron membrane, this additional membrane translocation of GLUT4 induces further glucose uptake and glucokinase-mediated glycolysis as well as ATP production [119]. This rise in intracellular ATP promotes inhibition of ATP sensitive K + (K ATP ) channels, which express in SON oxytocin neurons (Fig.…”

Section: The Regulation Of Son Oxytocin Neuronsmentioning

confidence: 99%

“…This rise in intracellular ATP promotes inhibition of ATP sensitive K + (K ATP ) channels, which express in SON oxytocin neurons (Fig. 2), and induce membrane depolarization and action potential firing, ultimately leading to oxytocin release [119]. This model could indicate that SON oxytocin neurons may function as glucose/metabolic sensors and participate in food intake regulation; however, further study is required.…”

Section: The Regulation Of Son Oxytocin Neuronsmentioning

confidence: 99%

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The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication

et al. 2018

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Oxytocin was discovered in 1906 as a peptide that promotes delivery and milk ejection; however, its additional physiological functions were determined 100 years later. Many recent articles have reported newly discovered effects of oxytocin on social communication, bonding, reward-related behavior, adipose tissue, and muscle and food intake regulation. Because oxytocin neurons project to various regions in the brain that contribute to both feeding reward (hedonic feeding) and the regulation of energy balance (homeostatic feeding), the mechanisms of oxytocin on food intake regulation are complicated and largely unknown. Oxytocin neurons in the paraventricular nucleus (PVN) receive neural projections from the arcuate nucleus (ARC), which is an important center for feeding regulation. On the other hand, these neurons in the PVN and supraoptic nucleus project to the ARC. PVN oxytocin neurons also project to the brain stem and the reward-related limbic system. In addition to this, oxytocin induces lipolysis and decreases fat mass. However, these effects in feeding and adipose tissue are known to be dependent on body weight (BW). Oxytocin treatment is more effective in food intake regulation and fat mass decline for individuals with leptin resistance and higher BW, but is known to be less effective in individuals with normal BW. In this review, we present in detail the recent findings on the physiological role of oxytocin in feeding regulation and the anorexigenic neural pathway of oxytocin neurons, as well as the advantage of oxytocin usage for anti-obesity treatment.

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Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

Cited by 52 publications

References 88 publications

High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

Water intake disorder in a DEND syndrome afflicted patient with R50P mutation

The Anorexigenic Neural Pathways of Oxytocin and Their Clinical Implication

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