oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Neural pathways that control the glucose counterregulatory response  [PDF]
Anthony J. M. Verberne,Azadeh Sabetghadam,Willian S. Korim
Frontiers in Neuroscience , 2014, DOI: 10.3389/fnins.2014.00038
Abstract: Glucose is an essential metabolic substrate for all bodily tissues. The brain depends particularly on a constant supply of glucose to satisfy its energy demands. Fortunately, a complex physiological system has evolved to keep blood glucose at a constant level. The consequences of poor glucose homeostasis are well-known: hyperglycemia associated with uncontrolled diabetes can lead to cardiovascular disease, neuropathy and nephropathy, while hypoglycemia can lead to convulsions, loss of consciousness, coma, and even death. The glucose counterregulatory response involves detection of declining plasma glucose levels and secretion of several hormones including glucagon, adrenaline, cortisol, and growth hormone (GH) to orchestrate the recovery from hypoglycemia. Low blood glucose leads to a low brain glucose level that is detected by glucose-sensing neurons located in several brain regions such as the ventromedial hypothalamus, the perifornical region of the lateral hypothalamus, the arcuate nucleus (ARC), and in several hindbrain regions. This review will describe the importance of the glucose counterregulatory system and what is known of the neurocircuitry that underpins it.
Effects of prostaglandin E2 on the electrical properties of thermally classified neurons in the ventromedial preoptic area of the rat hypothalamus
Heather J Ranels, John D Griffin
BMC Neuroscience , 2005, DOI: 10.1186/1471-2202-6-14
Abstract: To characterize the electrical properties of VMPO neurons, whole-cell recordings were made in tissue slices from male Sprague-Dawley rats. Our results indicate that PGE2 dependent firing rate responses were not the result of changes in resting membrane potential, action potential amplitude and duration, or local synaptic input. However, PGE2 reduced the input resistance of all VMPO neurons, while increasing the excitability of temperature insensitive neurons and decreasing the excitability of warm sensitive neurons. In addition, the majority of temperature insensitive neurons responded to PGE2 with an increase in the rate of rise of the depolarizing prepotential that precedes each action potential. This response to PGE2 was reversed for warm sensitive neurons, in which the prepotential rate of rise decreased.We would therefore suggest that PGE2 is having an effect on the ionic currents that regulate firing rate by controlling how fast membrane potential rises to threshold during the prepotential phase of the action potential.Fever, an elevation in body temperature, is thought to play an adaptive role in the immune system's ability to fight infection [1]. A suggested mechanism for its production and maintenance is a shifting of the thermostatic set-point into the hyperthermic range [1,2]. Through the integration of both central and afferent thermal information, this set-point is established by the activity of neurons in the preoptic and anterior regions of the hypothalamus (PO/AH) that can be thermally classified on the basis of their inherent ability to respond to changes in temperature [3]. The majority of PO/AH neurons are considered temperature insensitive, showing little or no temperature dependent changes in firing rate. Approximately 30% of PO/AH neurons can be classified as warm sensitive, responding to local warming with an increase in firing rate [4]. While there has been considerable debate as to the criteria that should be used to classify a neuron as war
Hypothalamic glucose sensing: making ends meet  [PDF]
Vanessa Routh,Zhenyu Sheng,Chunxue Zhou
Frontiers in Systems Neuroscience , 2014, DOI: 10.3389/fnsys.2014.00236
Abstract: The neuroendocrine system governs essential survival and homeostatic functions. For example, growth is needed for development. Thermoregulation maintains optimal core temperature in a changing environment. Reproduction ensures species survival. Stress and immune responses enable an organism to overcome external and internal threats. The circadian system regulates arousal and sleep such that vegetative and active functions do not overlap. All of these functions require a significant portion of the body’s energy. As the integrator of the neuroendocrine system, the hypothalamus carefully assesses the energy status of the body in order to appropriately partition resources to provide for each system without compromising the others. While doing so the hypothalamus must ensure that adequate glucose levels are preserved for brain function since glucose is the primary fuel of the brain. To this end, the hypothalamus contains specialized glucose sensing neurons which are scattered throughout the nuclei controlling distinct neuroendocrine functions. We hypothesize that these neurons play a key role in enabling the hypothalamus to partition energy to meet these peripheral survival needs without endangering the brain’s glucose supply. The goal of this review is to describe the varied mechanisms underlying glucose sensing in neurons within discrete hypothalamic nuclei. We will then evaluate the way in which peripheral energy status regulates glucose sensitivity. For example, during energy deficit such as fasting specific hypothalamic glucose sensing neurons become sensitized to decreased glucose. This increases the gain of the information relay when glucose availability is a greater concern for the brain. Finally, changes in glucose sensitivity under pathological conditions (e.g., recurrent insulin-hypoglycemia, diabetes) will be addressed. The overall goal of this review is to place glucose sensing neurons within the context of hypothalamic control of neuroendocrine function.
Central Nervous System Control of Glucose Homeostasis  [PDF]
Poondy Gopalratnam Raman
Open Journal of Endocrine and Metabolic Diseases (OJEMD) , 2017, DOI: 10.4236/ojemd.2017.712020
Abstract: Hypothalamus and brain stem play important roles in Glucose Homeostasis. There are two types of cells in the hypothalamus: Glucose excited (GE) and Glucose inhibited (GI). GE increases glucose concentration and GI decreases glucose concentration. They are located in ventromedial (VMH), arcuate, lateral, dorsomedial and paraventricular areas of hypothalamus. Nucleus of solitary tract, area postrema, dorsomedial nucleus of vagus and basolateral medulla are also related to glucose homeostasis. VMH contains sympathetic nucleus and upregulates plasma glucose and decreases hepatic glycogen, while lateral hypothalamus contains parasympathetic and down regulates plasma glucose. Through Glut-1, dependent transport glucose enters neurons and astrocytes. Glucose is metabolized and provides energy for GE and GI neurons. Their activity is guided by blood sugar level. Blood sugar level sends numerous signals through vagal pathway from periphery. Neuron astrocyte establishes via autonomic system connections with liver, pancreas, adrenal gland and maintains glucose homeostasis. Post prandial glucose levels are regulated by CNS.
Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation  [PDF]
Hai Zhang,Guo Zhang,Frank J. Gonzalez,Sung-min Park,Dongsheng Cai
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001112
Abstract: Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.
Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation  [PDF]
Hai Zhang,Guo Zhang,Frank J. Gonzalez,Sung-min Park,Dongsheng Cai
PLOS Biology , 2011, DOI: 10.1371/journal.pbio.1001112
Abstract: Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.
Fasting Induced Cytoplasmic Fto expression in Some Neurons of Rat Hypothalamus  [PDF]
Predrag Vujovic, Stefan Stamenkovic, Nebojsa Jasnic, Iva Lakic, Sinisa F. Djurasevic, Gordana Cvijic, Jelena Djordjevic
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063694
Abstract: Fat mass and obesity associated protein (Fto) is a nucleic acid demethylase, with a preference for thymine or uracil, according to the recent structural data. This fact suggests that methylated single-stranded RNA, rather than DNA, may be the primary Fto substrate. Fto is abundantly expressed in all hypothalamic sites governing feeding behavior. Considering that selective modulation of Fto levels in the hypothalamus can influence food intake, we set out to investigate the effect of 48 h fasting on the Fto expression in lateral hypothalamic area, paraventricular, ventromedial and arcuate nucleus, the regulatory centres of energy homeostasis. We have demonstrated that 48 h fasting causes not only an increase in the overall hypothalamic levels of both Fto mRNA and protein, but also alters Fto intracellular distribution. This switch happens in some neurons of paraventricular and ventromedial nucleus, as well as lateral hypothalamic area, resulting in the majority of the enzyme being localized outside the cell nuclei. Interestingly, the change in the Fto intracellular localization was not observed in neurons of arcuate nucleus, suggesting that fasting did not universally affect Fto in all of the hypothalmic sites involved in energy homeostasis regulation. Both Fto mRNA and catechol-O-methyltransferaze mRNA were upregulated in the identical time-dependent manner in fasting animals. This fact, combined with the knowledge of the Fto substrate preference, may provide further insight into monoamine metabolism in the state of disturbed energy homeostasis.
GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus  [PDF]
Leire Reguero, Nagore Puente, Izaskun Elezgarai, Juan Mendizabal-Zubiaga, Miren Josune Canduela, Ianire Buceta, Almudena Ramos, Juan Suárez, Fernando Rodríguez de Fonseca, Giovanni Marsicano, Pedro Grandes
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026167
Abstract: Background Type-1 cannabinoid receptors (CB1R) are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that participates in homeostatic and behavioral functions including food intake. Although CB1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. Methodology/Principal Findings Light and electron microscopy techniques were used to analyze CB1R distribution in the VMH of CB1R-WT, CB1R-KO and conditional mutant mice bearing a selective deletion of CB1R in cortical glutamatergic (Glu-CB1R-KO) or GABAergic neurons (GABA-CB1R-KO). At light microscopy, CB1R immunolabeling was observed in the VMH of CB1R-WT and Glu-CB1R-KO animals, being remarkably reduced in GABA-CB1R-KO mice. In the electron microscope, CB1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB1R immunopositive profiles and CB1R density in terminals making asymmetric or symmetric synapses in CB1R-WT mice. Furthermore, the proportion of CB1R immunopositive terminals/preterminals in CB1R-WT and Glu-CB1R-KO mice was reduced in GABA-CB1R-KO mutants. CB1R density was similar in all animal conditions. Finally, the percentage of CB1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB1R-KO mutants relative to CB1R-WT mice, indicating that CB1R was distributed in cortical and subcortical excitatory synaptic terminals. Conclusions/Significance Our anatomical results support the idea that the VMH is a relevant hub candidate in the endocannabinoid-mediated modulation of the excitatory and inhibitory neurotransmission of cortical and subcortical pathways regulating essential hypothalamic functions for the individual's survival such as the feeding behavior.
Fatty Acid Transporter CD36 Mediates Hypothalamic Effect of Fatty Acids on Food Intake in Rats  [PDF]
Valentine S. Moullé, Christelle Le Foll, Erwann Philippe, Nadim Kassis, Claude Rouch, Nicolas Marsollier, Linh-Chi Bui, Christophe Guissard, Julien Dairou, Anne Lorsignol, Luc Pénicaud, Barry E. Levin, Céline Cruciani-Guglielmacci, Christophe Magnan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074021
Abstract: Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/? heparin (IL, ILH, respectively) or saline/heparin (SH) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with ILH/SH; and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with ILH/SH. ILH significantly lowered food intake during refeeding compared to SH (p<0.001). Five hours after refeeding, etomoxir did not affect this inhibitory effect of ILH on food intake while VMN CD36 depletion totally prevented it. Triacsin C also prevented ILH effects on food intake. In conclusion, the effect of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but does not required FA oxidation.
Central urocortin 3 and type 2 corticotropin-releasing factor receptor in the regulation of energy homeostasis: critical involvement of the ventromedial hypothalamus  [PDF]
Peilin Chen,Christine Van Hover,Daniel Lindberg,Chien Li
Frontiers in Endocrinology , 2013, DOI: 10.3389/fendo.2012.00180
Abstract: The vital role of the corticotropin-releasing factor (CRF) peptide family in the brain in coordinating response to stress has been extensively documented. The effects of CRF are mediated by two G-protein-coupled receptors, type 1 and type 2 CRF receptors (CRF1 and CRF2). While the functional role of CRF1 in hormonal and behavioral adaptation to stress is well-known, the physiological significance of CRF2 remains to be fully appreciated. Accumulating evidence has indicated that CRF2 and its selective ligands including urocortin 3 (Ucn 3) are important molecular mediators in regulating energy balance. Ucn 3 is the latest addition of the CRF family of peptides and is highly selective for CRF2. Recent studies have shown that central Ucn 3 is important in a number of homeostatic functions including suppression of feeding, regulation of blood glucose levels, and thermoregulation, thus reinforcing the functional role of central CRF2 in metabolic regulation. The brain loci that mediate the central effects of Ucn 3 remain to be fully determined. Anatomical and functional evidence has suggested that the ventromedial hypothalamus (VMH), where CRF2 is prominently expressed, appears to be instrumental in mediating the effects of Ucn 3 on energy balance, permitting Ucn 3-mediated modulation of feeding and glycemic control. Thus, the Ucn 3-VMH CRF2 system is an important neural pathway in the regulation of energy homeostasis and potentially plays a critical role in energy adaptation in response to metabolic perturbations and stress to maintain energy balance.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.