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Sample records for brain glucose metabolism

  1. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  2. Glucose metabolism, diet composition, and the brain

    NARCIS (Netherlands)

    Diepenbroek, C.

    2017-01-01

    Excessive intake of saturated fat and sugar contributes to both obesity and diabetes development. Since intake of fat and sugar-sweetened beverages exceeds recommended levels worldwide, it is essential to: 1) Understand how fat and sugar intake affect glucose metabolism, and 2) Expand the knowledge

  3. Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

    Science.gov (United States)

    Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

    2011-01-01

    OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

  4. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between...

  5. Linking neuronal brain activity to the glucose metabolism.

    Science.gov (United States)

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-08-29

    Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

  6. Brain glucose metabolism in an animal model of depression.

    Science.gov (United States)

    Detka, J; Kurek, A; Kucharczyk, M; Głombik, K; Basta-Kaim, A; Kubera, M; Lasoń, W; Budziszewska, B

    2015-06-04

    An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on α-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to

  7. Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

    Science.gov (United States)

    Kurtz, Pedro; Claassen, Jan; Schmidt, J Michael; Helbok, Raimund; Hanafy, Khalid A; Presciutti, Mary; Lantigua, Hector; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A

    2013-12-01

    The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

  8. Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies.

    Science.gov (United States)

    Rooijackers, Hanne M M; Wiegers, Evita C; Tack, Cees J; van der Graaf, Marinette; de Galan, Bastiaan E

    2016-02-01

    Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain's handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

  9. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

    2007-06-15

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  10. Effects of MDMA on blood glucose levels and brain glucose metabolism

    International Nuclear Information System (INIS)

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M.; Arango, C.; Ricaurte, G.

    2007-01-01

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  11. Cerebral Glucose Metabolism and Sedation in Brain-injured Patients: A Microdialysis Study.

    Science.gov (United States)

    Hertle, Daniel N; Santos, Edgar; Hagenston, Anna M; Jungk, Christine; Haux, Daniel; Unterberg, Andreas W; Sakowitz, Oliver W

    2015-07-01

    Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical (1 mmol/L) extracellular brain glucose levels. We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (Pbrain glucose levels, extracellular brain glucose was unaffected by any type of sedative. These findings suggest that the use of anesthetic drugs may be of limited value in attempts to influence brain glucose metabolism in injured brain tissue.

  12. Effects of lithium on brain glucose metabolism in healthy men.

    Science.gov (United States)

    Kohno, Tomoya; Shiga, Tohru; Toyomaki, Atsuhito; Kusumi, Ichiro; Matsuyama, Tetsuaki; Inoue, Tetsuya; Katoh, Chietsugu; Koyama, Tsukasa; Tamaki, Nagara

    2007-12-01

    Lithium is clinically available for the treatment of mood disorders. However, it has remained unclear how lithium acts on the brain to produce its effects. The aim of this study was to evaluate the effects of chronic lithium on human brain activity using positron emission tomography and clarify the correlation between brain activity changes and cognitive functional changes as induced by chronic lithium administration. A total of 20 healthy male subjects (mean age, 32 +/- 6 years) underwent positron emission tomographic scans with F-fluorodeoxyglucose and a battery of neuropsychological tests at baseline condition and after 4 weeks of lithium administration. Brain metabolic data were analyzed using statistical parametric mapping. Lithium increased relative regional cerebral glucose metabolism (rCMRglc) in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased rCMRglc in the right cerebellum and left lingual gyrus/cuneus. There was no difference in any of the variables of cognitive functions between the baseline condition and after chronic lithium administration. There was no correlation between rCMRglc changes in any of the brain regions and individual variable changes in any of the neuropsychological tests. The results suggest that the effects of chronic lithium are associated with increased activity in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased activity in the right cerebellum and left lingual gyrus/cuneus.

  13. Brain areas and pathways in the regulation of glucose metabolism

    NARCIS (Netherlands)

    Diepenbroek, Charlene; Serlie, Mireille J.; Fliers, Eric; Kalsbeek, Andries; la Fleur, Susanne E.

    2013-01-01

    Glucose is the most important source of fuel for the brain and its concentration must be kept within strict boundaries to ensure the organism's optimal fitness. To maintain glucose homeostasis, an optimal balance between glucose uptake and glucose output is required. Besides managing acute changes

  14. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    Science.gov (United States)

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  16. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

    Science.gov (United States)

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-03-11

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

  17. Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury

    OpenAIRE

    Meierhans, Roman; B?chir, Markus; Ludwig, Silke; Sommerfeld, Jutta; Brandi, Giovanna; Haberth?r, Christoph; Stocker, Reto; Stover, John F

    2010-01-01

    Introduction The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. Methods In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 ?l/min, collecting samples at 60 minute intervals. Occult metabolic alteratio...

  18. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    NARCIS (Netherlands)

    Cutts, DA; Maguire, RP; Leenders, KL; Spyrou, NM

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was

  19. Linking neuronal brain activity to the glucose metabolism

    OpenAIRE

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regul...

  20. Regional differences in brain glucose metabolism determined by imaging mass spectrometry

    OpenAIRE

    André Kleinridders; Heather A. Ferris; Michelle L. Reyzer; Michaela Rath; Marion Soto; M. Lisa Manier; Jeffrey Spraggins; Zhihong Yang; Robert C. Stanton; Richard M. Caprioli; C. Ronald Kahn

    2018-01-01

    Objective: Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). Metho...

  1. Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy

    Science.gov (United States)

    2007-03-30

    Tymoczko et al. 2002). Both cardiac muscle and brain contain the necessary enzymes to metabolize either glucose or ketone bodies . The enzymes... metabolic phenotype of astrocytes and neurons in vitro; and to determine whether antipsychotic drug administration affects glucose metabolites in...Cortical Astrocytes and Neurons 20 Abstract 21 v Introduction ~ 22 Results 24 Enriched Astrocyte and Neuronal Cultures Display Unique Metabolic

  2. Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose beneath 1 mM in patients with severe traumatic brain injury.

    OpenAIRE

    Meierhans, R; Bechir, M; Ludwig, S; Sommerfeld, J; Brandi, G; Haberthur, C; Stocker, R; Stover, J F

    2010-01-01

    ABSTRACT: INTRODUCTION: The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. METHODS: In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 mul/ min, collecting samples at 60 minute intervals. Occult metab...

  3. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid.

    Science.gov (United States)

    Castro, Maite A; Beltrán, Felipe A; Brauchi, Sebastián; Concha, Ilona I

    2009-07-01

    In this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K(+)]. Neurons are cells well equipped to consume glucose because they express glucose transporters and glycolytic and tricarboxylic acid cycle enzymes. Moreover, neuronal cells express monocarboxylate transporters and lactate dehydrogenase isoenzyme 1, which is inhibited by pyruvate. As glycolysis produces an increase in pyruvate concentration and a decrease in NAD(+)/NADH, lactate and glucose consumption are not viable at the same time. In this context, we discuss ascorbic acid participation as a metabolic switch modulating neuronal metabolism between rest and activation periods. Ascorbic acid is highly concentrated in CNS. Glutamate stimulates ascorbic acid release from astrocytes. Ascorbic acid entry into neurons and within the cell can inhibit glucose consumption and stimulate lactate transport. For this switch to occur, an ascorbic acid flow is necessary between astrocytes and neurons, which is driven by neural activity and is part of vitamin C recycling. Here, we review the role of glucose and lactate as metabolic substrates and the modulation of neuronal metabolism by ascorbic acid.

  4. Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.

    Science.gov (United States)

    Tuulari, Jetro J; Karlsson, Henry K; Hirvonen, Jussi; Hannukainen, Jarna C; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

    2013-08-01

    Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

  5. Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig

    NARCIS (Netherlands)

    van Hulst, Robert A.; Drenthen, Judith; Haitsma, Jack J.; Lameris, Thomas W.; Visser, Gerhard H.; Klein, Jan; Lachmann, Burkhard

    2005-01-01

    OBJECTIVE: To evaluate the effects of hyperbaric oxygen treatment after cerebral air embolism on intracranial pressure, brain oxygenation, brain glucose/lactate metabolism, and electroencephalograph. DESIGN: Prospective animal study. SETTING: Hyperbaric chamber. SUBJECTS: Eleven Landrace/Yorkshire

  6. Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

    Science.gov (United States)

    Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

    2016-06-01

    Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

  7. Thyroid hormone’s role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes

    Science.gov (United States)

    Jahagirdar, V; McNay, EC

    2012-01-01

    Cognitive performance is dependent on adequate glucose supply to the brain. Insulin, which regulates systemic glucose metabolism, has been recently shown both to regulate hippocampal metabolism and to be a mandatory component of hippocampally-mediated cognitive performance. Thyroid hormones (TH) regulate systemic glucose metabolism and may also be involved in regulation of brain glucose metabolism. Here we review potential mechanisms for such regulation. Importantly, TH imbalance is often encountered in combination with metabolic disorders, such as diabetes, and may cause additional metabolic dysregulation and hence worsening of disease states. TH’s potential as a regulator of brain glucose metabolism is heightened by interactions with insulin signaling, but there have been relatively few studies on this topic or on the actions of TH in a mature brain. This review discusses evidence for mechanistic links between TH, insulin, cognitive function, and brain glucose metabolism, and suggests that TH is a good candidate to be a modulator of memory processes, likely at least in part by modulation of central insulin signaling and glucose metabolism. PMID:22437199

  8. Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4 gene (VNTR in exon 3, which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET and [(18F]fluoro-D-glucose ((18FDG to measure brain glucose metabolism (marker of brain function under baseline conditions (no stimulation in 82 healthy individuals (age range 22-55 years. We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n = 53 had a significant (p<0.0001 negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism in frontal (r = -0.52, temporal (r = -0.51 and striatal regions (r = -0.47, p<0.001; such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29, these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002. Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

  9. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    Science.gov (United States)

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

  10. The Alzheimer's Disease-Related Glucose Metabolic Brain Pattern

    NARCIS (Netherlands)

    Teune, Laura K.; Strijkert, Fijanne; Renken, Remco J.; Izaks, Gerbrand J.; de Vries, Jeroen J.; Segbers, Marcel; Roerdink, Jos B. T. M.; Dierckx, Rudi A. J. O.; Leenders, Klaus L.

    2014-01-01

    Purpose: [F-18] fluorodeoxyglucose (FDG) PET imaging of the brain can be used to assist in the differential diagnosis of dementia. Group differences in glucose uptake between patients with dementia and controls are well-known. However, a multivariate analysis technique called scaled subprofile

  11. Regional brain glucose metabolism and blood flow in streptozocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Jakobsen, J.; Nedergaard, M.; Aarslew-Jensen, M.; Diemer, N.H.

    1990-01-01

    Brain regional glucose metabolism and regional blood flow were measured from autoradiographs by the uptake of [ 3 H]-2-deoxy-D-glucose and [ 14 C]iodoantipyrine in streptozocin-induced diabetic (STZ-D) rats. After 2 days of diabetes, glucose metabolism in the neocortex, basal ganglia, and white matter increased by 34, 37, and 8%, respectively, whereas blood flow was unchanged. After 4 mo, glucose metabolism in the same three regions was decreased by 32, 43, and 60%. This reduction was paralleled by a statistically nonsignificant reduction in blood flow in neocortex and basal ganglia. It is suggested that the decrease of brain glucose metabolism in STZ-D reflects increased ketone body oxidation and reduction of electrochemical work

  12. Relationship between regional brain glucose metabolism and temperament factor of personality

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

  13. Relationship between regional brain glucose metabolism and temperament factor of personality

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24±4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor

  14. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  15. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    International Nuclear Information System (INIS)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-01-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions

  16. Control of Hepatic Glucose Metabolism by Islet and Brain

    Science.gov (United States)

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  17. Metabolism of glucose in brain of patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki.

    1984-01-01

    We examined 11 C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with 11 C-glucose (per os). 11 C-glucose was prepared from 11 CO 2 by photosynthesis. 1) No significant difference was observed in the 11 C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the 11 C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author)

  18. Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

    Science.gov (United States)

    Haier, Richard J.; And Others

    1995-01-01

    Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

  19. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  20. Glucose metabolism and astrocyte-neuron interactions in the neonatal brain.

    Science.gov (United States)

    Brekke, Eva; Morken, Tora Sund; Sonnewald, Ursula

    2015-03-01

    Glucose is essentially the sole fuel for the adult brain and the mapping of its metabolism has been extensive in the adult but not in the neonatal brain, which is believed to rely mainly on ketone bodies for energy supply. However, glucose is absolutely indispensable for normal development and recent studies have shed light on glycolysis, the pentose phosphate pathway and metabolic interactions between astrocytes and neurons in the 7-day-old rat brain. Appropriately (13)C labeled glucose was used to distinguish between glycolysis and the pentose phosphate pathway during development. Experiments using (13)C labeled acetate provided insight into the GABA-glutamate-glutamine cycle between astrocytes and neurons. It could be shown that in the neonatal brain the part of this cycle that transfers glutamine from astrocytes to neurons is operating efficiently while, in contrast, little glutamate is shuttled from neurons to astrocytes. This lack of glutamate for glutamine synthesis is compensated for by anaplerosis via increased pyruvate carboxylation relative to that in the adult brain. Furthermore, compared to adults, relatively more glucose is prioritized to the pentose phosphate pathway than glycolysis and pyruvate dehydrogenase activity. The reported developmental differences in glucose metabolism and neurotransmitter synthesis may determine the ability of the brain at various ages to resist excitotoxic insults such as hypoxia-ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Assessment of regional glucose metabolism in aging brain and dementia with positron-emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Reivich, M.; Alavi, A.; Ferris, S.; Christman, D.; Fowler, J.; MacGregor, R.; Farkas, T.; Greenberg, J.; Dann, R.; Wolf, A.

    1981-01-01

    This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patients with dementia although this did not reach the level of significance when compared to the elderly control subjects. The changes in glucose metabolism were symmetrical in both the left and right hemispheres. There was a lack of correlation between the mean cortical metabolic rates for glucose and the global mental function in the patients with senile dementia. This is at variance with most of the regional cerebral blood flow data that has been collected. This may be partly related to the use of substrates other than glucose by the brain in elderly and demented subjects. (PSB)

  2. Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

    Science.gov (United States)

    Amaral, Ana I

    2013-07-01

    Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

  3. Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

    Science.gov (United States)

    Li, Wei-Ling; Fu, Chang; Xuan, Ang; Shi, Da-Peng; Gao, Yong-Ju; Zhang, Jie; Xu, Jun-Ling

    2015-02-05

    Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  4. Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

    Directory of Open Access Journals (Sweden)

    Wei-Ling Li

    2015-01-01

    Full Text Available Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People′s Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases, squamous cell carcinoma (43 cases, and small-cell carcinoma (25 cases. The whole body 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/computed tomography (CT of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255 was larger than those in the adenocarcinoma group (total voxel value 1217 and squamous cell carcinoma group (total voxel value 1292. Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  5. Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients

    DEFF Research Database (Denmark)

    Stender, Johan; Kupers, Ron; Rodell, Anders

    2015-01-01

    of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global......The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function...... these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.Journal of Cerebral Blood Flow & Metabolism advance online publication, 8 October 2014; doi:10...

  6. Generalized decrease in brain glucose metabolism during fasting in humans studied by PET

    International Nuclear Information System (INIS)

    Redies, C.; Hoffer, L.J.; Beil, C.

    1989-01-01

    In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged

  7. Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism

    Science.gov (United States)

    Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Vaska, Paul; Fowler, Joanna S.; Telang, Frank; Alexoff, Dave; Logan, Jean; Wong, Christopher

    2011-01-01

    Context The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. Objective To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Design, Setting, and Participants Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with (18F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes (“on” condition) and once with both cell phones deactivated (“off” condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm3) and P < .05 (corrected for multiple comparisons) were considered significant. Main Outcome Measure Brain glucose metabolism computed as absolute metabolism (µmol/100 g per minute) and as normalized metabolism (region/whole brain). Results Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 µmol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67–4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001

  8. Brain glucose and acetoacetate metabolism: a comparison of young and older adults.

    Science.gov (United States)

    Nugent, Scott; Tremblay, Sebastien; Chen, Kewei W; Ayutyanont, Napatkamon; Roontiva, Auttawut; Castellano, Christian-Alexandre; Fortier, Melanie; Roy, Maggie; Courchesne-Loyer, Alexandre; Bocti, Christian; Lepage, Martin; Turcotte, Eric; Fulop, Tamas; Reiman, Eric M; Cunnane, Stephen C

    2014-06-01

    The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Dynamic brain glucose metabolism identifies anti-correlated cortical-cerebellar networks at rest.

    Science.gov (United States)

    Tomasi, Dardo G; Shokri-Kojori, Ehsan; Wiers, Corinde E; Kim, Sunny W; Demiral, Şukru B; Cabrera, Elizabeth A; Lindgren, Elsa; Miller, Gregg; Wang, Gene-Jack; Volkow, Nora D

    2017-12-01

    It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns in 53 healthy participants at rest. Twenty-two rfMRI networks emerged from group independent component analysis (gICA). In contrast, only two anti-correlated t-MC emerged from FDG-PET time series using gICA or seed-voxel correlations; one included frontal, parietal and temporal cortices, the other included the cerebellum and medial temporal regions. Whereas cerebellum, thalamus, globus pallidus and calcarine cortex arose as the strongest t-MC hubs, the precuneus and visual cortex arose as the strongest rfMRI hubs. The strength of the t-MC linearly increased with the metabolic rate of glucose suggesting that t-MC measures are strongly associated with the energy demand of the brain tissue, and could reflect regional differences in glucose metabolism, counterbalanced metabolic network demand, and/or differential time-varying delivery of FDG. The mismatch between metabolic and functional connectivity patterns computed as a function of time could reflect differences in the temporal characteristics of glucose metabolism as measured with PET-FDG and brain activation as measured with rfMRI.

  10. Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

    Science.gov (United States)

    Konitzer, K.; Voigt, S.

    1980-01-01

    Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

  11. Reversible changes in brain glucose metabolism following thyroid function normalization in hyperthyroidism.

    Science.gov (United States)

    Miao, Q; Zhang, S; Guan, Y H; Ye, H Y; Zhang, Z Y; Zhang, Q Y; Xue, R D; Zeng, M F; Zuo, C T; Li, Y M

    2011-01-01

    Patients with hyperthyroidism frequently present with regional cerebral metabolic changes, but the consequences of endocrine-induced brain changes after thyroid function normalization are unclear. We hypothesized that the changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroid, and some of these changes can be reversed with antithyroid therapy. Relative regional cerebral glucose metabolism was compared between 10 new-onset untreated patients with hyperthyroidism and 20 healthy control participants by using brain FDG-PET scans. Levels of emotional distress were evaluated by using the SAS and SDS. Patients were treated with methimazole. A follow-up PET scan was performed to assess metabolic changes of the brain when thyroid functions normalized. Compared with controls, patients exhibited lower activity in the limbic system, frontal lobes, and temporal lobes before antithyroid treatment. There were positive correlations between scores of depression and regional metabolism in the cingulate and paracentral lobule. The severity of depression and anxiety covaried negatively with pretreatment activity in the inferior temporal and inferior parietal gyri respectively. Compared with the hyperthyroid status, patients with normalized thyroid functions showed an increased metabolism in the left parahippocampal, fusiform, and right superior frontal gyri. The decrease in both FT3 and FT4 was associated with increased activity in the left parahippocampal and right superior frontal gyri. The changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroidism, and some cerebral hypometabolism can be improved after antithyroid therapy.

  12. Low doses of alcohol substantially decrease glucose metabolism in the human brain.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Franceschi, Dinko; Fowler, Joanna S; Thanos, Panayotis Peter K; Maynard, Laurence; Gatley, S John; Wong, Christopher; Veech, Richard L; Kunos, George; Kai Li, Ting

    2006-01-01

    Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

  13. Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

    Science.gov (United States)

    Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

    2016-10-01

    This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Functional integration changes in regional brain glucose metabolism from childhood to adulthood.

    Science.gov (United States)

    Trotta, Nicola; Archambaud, Frédérique; Goldman, Serge; Baete, Kristof; Van Laere, Koen; Wens, Vincent; Van Bogaert, Patrick; Chiron, Catherine; De Tiège, Xavier

    2016-08-01

    The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. It is determined whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was examined in a group of 72 subjects, ages 22 to 82 years, with 36 regions of interest chosen from both hemispheres of the cortex, midbrain and cerebellum. To determine metabolic rates the in-vivo technique of positron emission tomography (PET) was employed. Three age groups were chosen to compare hemispherical differences. In both young and intermediate age groups the left hemisphere had higher rCMRGlu values than those of the right for the majority of regions with, although less pronounced in the intermediate group. Importantly, the older age group displayed little difference between hemispheres. (author)

  16. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    International Nuclear Information System (INIS)

    Wong, K.L.; Tyce, G.M.

    1983-01-01

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U- 14 C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

  17. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    Energy Technology Data Exchange (ETDEWEB)

    Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Largo P. Daneo, 3, 16132, Genoa (Italy); Polidori, M.C. [University of Cologne, Institute of Geriatrics, Cologne (Germany); Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia [University of Perugia, Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS San Martino-IST, Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Fiorucci, Giuliana; Dottorini, Massimo Eugenio [Nuclear Medicine, S. M. della Misericordia Hospital, Perugia (Italy)

    2014-04-15

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain{sup 18}F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  18. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    International Nuclear Information System (INIS)

    Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio; Polidori, M.C.; Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia; Morbelli, Silvia; Bossert, Irene; Fiorucci, Giuliana; Dottorini, Massimo Eugenio

    2014-01-01

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain 18 F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  19. Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients.

    Science.gov (United States)

    Stender, Johan; Kupers, Ron; Rodell, Anders; Thibaut, Aurore; Chatelle, Camille; Bruno, Marie-Aurélie; Gejl, Michael; Bernard, Claire; Hustinx, Roland; Laureys, Steven; Gjedde, Albert

    2015-01-01

    The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.

  20. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    Directory of Open Access Journals (Sweden)

    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  1. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

  2. 13C NMR for the assessment of human brain glucose metabolism in vivo

    International Nuclear Information System (INIS)

    Beckman, N.; Seelig, J.; Turkalj, I.; Keller, U.

    1991-01-01

    Proton-decoupled 13 C NMR spectra of the human head were obtained during hyperglycemic glucose clamping using intravenous infusions of [1- 13 C]glucose in normal volunteers. In addition to 13 C signals of mobile lipids, a variety of new metabolite resonances could be resolved for the first time in the human brain. At an enrichment level of 20% [1- 13 C]glucose, the signals of α- and β-glucose at 92.7 and 96.6 ppm, respectively, could be detected in the human brain after only an infusion period of 15 minutes. The spatial localization of the different regions of interest was confirmed by 13 C NMR spectroscopic imaging with a time resolution of 9 minutes. Increasing the enrichment level to 99% [1- 13 C]glucose not only improved the time resolution but allowed the detection of metabolic breakdown products of [1- 13 C]glucose. The time course of 13 C label incorporation into the C 2 , C 3 , and C 4 resonances of glutamate/glutamine and into lactate could be recorded in the human brain. These results suggest the possibility of obtaining time-resolved, spatially selective, and chemically specific information on the human body

  3. Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose

    Energy Technology Data Exchange (ETDEWEB)

    Dyve, S [Department of General Physiology and Biophysics, Panum Institute, Copenhagen (Denmark); Gjedde, A [Positron Imaging Laboratories, McConnell Brain Imaging Center, Montreal, Quebec (Canada)

    1991-01-01

    Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 +- 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 +- 2 {mu}mol hg{sup -1} min{sup -1}. (author).

  4. Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

    Science.gov (United States)

    Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna; Vilchez, Crystal; Veith, Jennifer; Brodie, Jonathan D; Dewey, Stephen L

    2017-08-01

    Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18 FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic

  5. Ethylene glycol ethers induce apoptosis and disturb glucose metabolism in the rat brain.

    Science.gov (United States)

    Pomierny, Bartosz; Krzyżanowska, Weronika; Niedzielska, Ewa; Broniowska, Żaneta; Budziszewska, Bogusława

    2016-02-01

    Ethylene glycol ethers (EGEs) are compounds widely used in industry and household products, but their potential, adverse effect on brain is poorly understood, so far. The aim of the present study was to determine whether 4-week administration of 2-buthoxyethanol (BE), 2-phenoxyethanol (PHE), and 2-ethoxyethanol (EE) induces apoptotic process in the rat hippocampus and frontal cortex, and whether their adverse effect on the brain cells can result from disturbances in the glucose metabolism. Experiments were conducted on 40 rats, exposed to BE, PHE, EE, saline or sunflower oil for 4 weeks. Markers of apoptosis and glucose metabolism were determined in frontal cortex and hippocampus by western blot, ELISA, and fluorescent-based assays. BE and PHE, but not EE, increased expression of the active form of caspase-3 in the examined brain regions. BE and PHE increased caspase-9 level in the cortex and PHE also in the hippocampus. BE and PHE increased the level of pro-apoptotic proteins (Bax, Bak) and/or reduced the concentration of anti-apoptotic proteins (Bcl-2, Bcl-xL); whereas, the effect of BE was observed mainly in the cortex and that of PHE in the hippocampus. It has also been found that PHE increased brain glucose level, and both BE and PHE elevated pyruvate and lactate concentration. It can be concluded that chronic treatment with BE and PHE induced mitochondrial pathway of apoptosis, and disturbed glucose metabolism in the rat brain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Study of cerebral metabolism of glucose in normal human brain correlated with age

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  7. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

    1999-01-01

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  8. Initial investigation of glucose metabolism in mouse brain using enriched 17 O-glucose and dynamic 17 O-MRS.

    Science.gov (United States)

    Borowiak, Robert; Reichardt, Wilfried; Kurzhunov, Dmitry; Schuch, Christian; Leupold, Jochen; Krafft, Axel Joachim; Reisert, Marco; Lange, Thomas; Fischer, Elmar; Bock, Michael

    2017-08-01

    In this initial work, the in vivo degradation of 17 O-labeled glucose was studied during cellular glycolysis. To monitor cellular glucose metabolism, direct 17 O-magnetic resonance spectroscopy (MRS) was used in the mouse brain at 9.4 T. Non-localized spectra were acquired with a custom-built transmit/receive (Tx/Rx) two-turn surface coil and a free induction decay (FID) sequence with a short TR of 5.4 ms. The dynamics of labeled oxygen in the anomeric 1-OH and 6-CH 2 OH groups was detected using a Hankel-Lanczos singular value decomposition (HLSVD) algorithm for water suppression. Time-resolved 17 O-MRS (temporal resolution, 42/10.5 s) was performed in 10 anesthetized (1.25% isoflurane) mice after injection of a 2.2 M solution containing 2.5 mg/g body weight of differently labeled 17 O-glucose dissolved in 0.9% physiological saline. From a pharmacokinetic model fit of the H 2 17 O concentration-time course, a mean apparent cerebral metabolic rate of 17 O-labeled glucose in mouse brain of CMR Glc  = 0.07 ± 0.02 μmol/g/min was extracted, which is of the same order of magnitude as a literature value of 0.26 ± 0.06 μmol/g/min reported by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET). In addition, we studied the chemical exchange kinetics of aqueous solutions of 17 O-labeled glucose at the C1 and C6 positions with dynamic 17 O-MRS. In conclusion, the results of the exchange and in vivo experiments demonstrate that the C6- 17 OH label in the 6-CH 2 OH group is transformed only glycolytically by the enzyme enolase into the metabolic end-product H 2 17 O, whereas C1- 17 OH ends up in water via direct hydrolysis as well as glycolysis. Therefore, dynamic 17 O-MRS of highly labeled 17 O-glucose could provide a valuable non-radioactive alternative to FDG PET in order to investigate glucose metabolism. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    WANG Qiong; LI Ai-lin; ZHI Da-shi; HUANG Hui-ling

    2007-01-01

    Objective:To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (STBI) using clinical microdialysis.Methods: Thirty-one patients with STBI ( GCS ≤8) were randomly divided into hypothermic group (Group A) and control group (Group B). Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA microdialysis analyzer.Results: In comparison with the control group, lactate/glucose ratio ( L/G) , lactate/pyruvate ratio ( L/P) and glycerol (Gly) in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perilensional tissue was higher than that in relative normal brain.Conclusions: Mild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in "normal brain" tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.

  10. Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

    Science.gov (United States)

    Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

    2012-07-01

    Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    International Nuclear Information System (INIS)

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

  12. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

  13. Glucose and oxygen metabolism after penetrating ballistic-like brain injury

    Science.gov (United States)

    Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies. PMID:25669903

  14. Maternal high-fat feeding leads to alterations of brain glucose metabolism in the offspring: positron emission tomography study in a porcine model.

    Science.gov (United States)

    Sanguinetti, Elena; Liistro, Tiziana; Mainardi, Marco; Pardini, Silvia; Salvadori, Piero A; Vannucci, Alessandro; Burchielli, Silvia; Iozzo, Patricia

    2016-04-01

    Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders. We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4. At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.

  15. Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice.

    Science.gov (United States)

    Wang, Pengwen; Su, Caixin; Feng, Huili; Chen, Xiaopei; Dong, Yunfang; Rao, Yingxue; Ren, Ying; Yang, Jinduo; Shi, Jing; Tian, Jinzhou; Jiang, Shucui

    2017-03-01

    Recent studies have shown the therapeutic potential of curcumin in Alzheimer's disease (AD). In 2014, our lab found that curcumin reduced Aβ40, Aβ42 and Aβ-derived diffusible ligands in the mouse hippocampus, and improved learning and memory. However, the mechanisms underlying this biological effect are only partially known. There is considerable evidence in brain metabolism studies indicating that AD might be a brain-specific type of diabetes with progressive impairment of glucose utilisation and insulin signalling. We hypothesised that curcumin might target both the glucose metabolism and insulin signalling pathways. In this study, we monitored brain glucose metabolism in living APPswe/PS1dE9 double transgenic mice using a micro-positron emission tomography (PET) technique. The study showed an improvement in cerebral glucose uptake in AD mice. For a more in-depth study, we used immunohistochemical (IHC) staining and western blot techniques to examine key factors in both glucose metabolism and brain insulin signalling pathways. The results showed that curcumin ameliorated the defective insulin signalling pathway by upregulating insulin-like growth factor (IGF)-1R, IRS-2, PI3K, p-PI3K, Akt and p-Akt protein expression while downregulating IR and IRS-1. Our study found that curcumin improved spatial learning and memory, at least in part, by increasing glucose metabolism and ameliorating the impaired insulin signalling pathways in the brain.

  16. Multifunctional roles of enolase in Alzheimer's disease brain: beyond altered glucose metabolism.

    Science.gov (United States)

    Butterfield, D Allan; Lange, Miranda L Bader

    2009-11-01

    Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer's disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, as there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified alpha-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD, and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, alpha-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, early-onset AD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder.

  17. Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course

    DEFF Research Database (Denmark)

    Mansur, Rodrigo B; Santos, Camila M; Rizzo, Lucas B

    2016-01-01

    OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism......, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (Psuicide attempts (P=.021). IGM moderated...... the association between BDNF and the number of previous mood episodes (P

  18. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism

    DEFF Research Database (Denmark)

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke

    2016-01-01

    In animal models, the incretin hormone GLP-1 affects Alzheimer's disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients...... with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe...

  19. Glucose transportation in the brain and its impairment in Huntington disease: one more shade of the energetic metabolism failure?

    Science.gov (United States)

    Morea, Veronica; Bidollari, Eris; Colotti, Gianni; Fiorillo, Annarita; Rosati, Jessica; De Filippis, Lidia; Squitieri, Ferdinando; Ilari, Andrea

    2017-07-01

    Huntington's disease (HD) or Huntington's chorea is the most common inherited, dominantly transmitted, neurodegenerative disorder. It is caused by increased CAG repeats number in the gene coding for huntingtin (Htt) and characterized by motor, behaviour and psychiatric symptoms, ultimately leading to death. HD patients also exhibit alterations in glucose and energetic metabolism, which result in pronounced weight loss despite sustained calorie intake. Glucose metabolism decreases in the striatum of all the subjects with mutated Htt, but affects symptom presentation only when it drops below a specific threshold. Recent evidence points at defects in glucose uptake by the brain, and especially by neurons, as a relevant component of central glucose hypometabolism in HD patients. Here we review the main features of glucose metabolism and transport in the brain in physiological conditions and how these processes are impaired in HD, and discuss the potential ability of strategies aimed at increasing intracellular energy levels to counteract neurological and motor degeneration in HD patients.

  20. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  1. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  2. Study of the brain glucose metabolism in different stage of mixed-type multiple system atrophy

    International Nuclear Information System (INIS)

    Wang Ying; Zhang Benshu; Cai Li; Zhang Meiyun; Gao Shuo

    2014-01-01

    Objective: To investigate the brain glucose metabolism in different stage of mixed-type multiple system atrophy (MSA). Methods: Forty-six MSA patients with cerebellar or Parkinsonian symptoms and 18 healthy controls with similar age as patients were included. According to the disease duration,the patients were divided into three groups: group 1 (≤ 12 months, n=14), group 2 (13-24 months, n=13), group 3 (≥ 25 months, n=19). All patients and controls underwent 18 F-FDG PET/CT brain imaging. To compare metabolic distributions between different groups, SPM 8 software and two-sample t test were used for image data analysis. When P<0.005, the result was considered statistically significant. Results: At the level of P<0.005, the hypometabolism in group 1 (all t>3.49) was identified in the frontal lobe, lateral temporal lobe, insula lobe, anterior cingulate cortex, caudate nucleus and anterior cerebellar hemisphere. The regions of hypometabolism extended to posterolateral putamen and part of posterior cerebellar hemisphere in group 2 (all t>3.21). In group 3, the whole parts of putamen and cerebellar hemisphere were involved as hypometabolism (all t>4.08). In addition to the hypometabolism regions, there were also stabled hypermetabolism regions mainly in the parietal lobe, medial temporal lobe and the thalamus in all patient groups (all t>3.27 in group 1, all t>3.02 in group 2,all t>3.30 in group 3). Conclusions: Disease duration is closely related to the FDG metabolism in the MSA patients. Frontal lobe, lateral temporal lobe, anterior cingulate cortex and caudate nucleus can be involved at early stage of the disease. Putaminal hypometabolism begins in its posterolateral part. Cerebellar hypometabolism occurs early at its anterior part. Besides, thalamus shows hypermetabolism in the whole duration. 18 F-FDG metabolic changes of brain can reflect the development of mixed-type MSA. (authors)

  3. Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

    Institute of Scientific and Technical Information of China (English)

    Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

    2006-01-01

    BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

  4. D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    International Nuclear Information System (INIS)

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V.

    1990-01-01

    We used D-[U-11C]glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-[U-11C]-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia [arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects]. Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects

  5. Simultaneous measurement of glucose blood–brain transport constants and metabolic rate in rat brain using in-vivo 1H MRS

    Science.gov (United States)

    Du, Fei; Zhang, Yi; Zhu, Xiao-Hong; Chen, Wei

    2012-01-01

    Cerebral glucose consumption and glucose transport across the blood–brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMRglc) and glucose transport constants (KT: half-saturation constant; Tmax: maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMRglc, KT, and Tmax via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo 1H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMRglc, Tmax, and KT were determined to be 0.44±0.17 μmol/g per minute, 1.35±0.47 μmol/g per minute, and 13.4±6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMRglc and Tmax are more reliable than that of KT. The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application. PMID:22714049

  6. Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment.

    Science.gov (United States)

    Porto, Fábio Henrique de Gobbi; Coutinho, Artur Martins Novaes; Pinto, Ana Lucia de Sá; Gualano, Bruno; Duran, Fabio Luís de Souza; Prando, Silvana; Ono, Carla Rachel; Spíndola, Lívia; de Oliveira, Maira Okada; do Vale, Patrícia Helena Figuerêdo; Nitrini, Ricardo; Buchpiguel, Carlos Alberto; Brucki, Sonia Maria Dozzi

    2015-01-01

    Aerobic training (AT) is a promising intervention for mild cognitive impairment (MCI). To evaluate the effects of AT on cognition and regional brain glucose metabolism (rBGM) in MCI patients. Subjects performed a twice-a-week, moderate intensity, AT program for 24 weeks. Assessment with ADAS-cog, a comprehensive neuropsychological battery, and evaluation of rBGM with positron emission tomography with 18F-fluorodeoxyglucose ([18F]FDG-PET) were performed before and after the intervention. Aerobic capacity was compared using the maximal oxygen consumption VO2max (mL/Kg/min). [18F]FDG-PET data were analyzed on a voxel-by-voxel basis with SPM8 software. Forty subjects were included, with a mean (M) age of 70.3 (5.4) years and an initial Mini-Mental State Exam score of 27.4 (1.7). Comparisons using paired t-tests revealed improvements in the ADAS-cog (M difference: -2.7 (3.7), p <  0.001) and VO2max scores (M difference: 1.8 (2.0) mL/kg/min, p <  0.001). Brain metabolic analysis revealed a bilateral decrease in the rBGM of the dorsal anterior cingulate cortex, pFWE = 0.04. This rBGM decrease was negatively correlated with improvement in a visuospatial function/attentional test (rho =-0.31, p = 0.04). Several other brain areas also showed increases or decreases in rBGM. Of note, there was an increase in the retrosplenial cortex, an important node of the default mode network, that was negatively correlated with the metabolic decrease in the dorsal anterior cingulate cortex (r =-0.51, p = 0.001). AT improved cognition and changed rBGM in areas related to cognition in subjects with MCI.

  7. Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.

    Science.gov (United States)

    Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

    2015-12-01

    There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.

  8. Glucose consumption of inflammatory cells masks metabolic deficits in the brain.

    Science.gov (United States)

    Backes, Heiko; Walberer, Maureen; Ladwig, Anne; Rueger, Maria A; Neumaier, Bernd; Endepols, Heike; Hoehn, Mathias; Fink, Gereon R; Schroeter, Michael; Graf, Rudolf

    2016-03-01

    Inflammatory cells such as microglia need energy to exert their functions and to maintain their cellular integrity and membrane potential. Subsequent to cerebral ischemia, inflammatory cells infiltrate tissue with limited blood flow where neurons and astrocytes died due to insufficient supply with oxygen and glucose. Using dual tracer positron emission tomography (PET), we found that concomitant with the presence of inflammatory cells, transport and consumption of glucose increased up to normal levels but returned to pathological levels as soon as inflammatory cells disappeared. Thus, inflammatory cells established sufficient glucose supply to satisfy their energy demands even in regions with insufficient supply for neurons and astrocytes to survive. Our data suggest that neurons and astrocytes died from oxygen deficiency and inflammatory cells metabolized glucose non-oxidatively in regions with residual availability. As a consequence, glucose metabolism of inflammatory cells can mask metabolic deficits in neurodegenerative diseases. We further found that the PET tracer did not bind to inflammatory cells in severely hypoperfused regions and thus only a part of the inflammation was detected. We conclude that glucose consumption of inflammatory cells should be taken into account when analyzing disease-related alterations of local cerebral metabolism. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.

    Science.gov (United States)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W; van Buchem, Mark A; Slagboom, P Eline; Westendorp, Rudi G; van Heemst, Diana; van der Grond, Jeroen

    2015-08-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging.

  10. Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury.

    Science.gov (United States)

    Vaquero, Jesús; Zurita, Mercedes; Bonilla, Celia; Fernández, Cecilia; Rubio, Juan J; Mucientes, Jorge; Rodriguez, Begoña; Blanco, Edelio; Donis, Luis

    2017-01-01

    Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs). Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 10 6 (one patient), 100 × 10 6 (one patient) and 300 × 10 6 (one patient). All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism. Our present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  11. Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

    Science.gov (United States)

    Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

    2013-01-01

    Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

  12. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    Science.gov (United States)

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

  13. Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

    Science.gov (United States)

    Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

    2016-06-01

    There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

  14. Metabolic fate of glucose in rats with traumatic brain injury and pyruvate or glucose treatments: A NMR spectroscopy study.

    Science.gov (United States)

    Shijo, Katsunori; Sutton, Richard L; Ghavim, Sima S; Harris, Neil G; Bartnik-Olson, Brenda L

    2017-01-01

    Administration of sodium pyruvate (SP; 9.08 μmol/kg, i.p.), ethyl pyruvate (EP; 0.34 μmol/kg, i.p.) or glucose (GLC; 11.1 μmol/kg, i.p.) to rats after unilateral controlled cortical impact (CCI) injury has been reported to reduce neuronal loss and improve cerebral metabolism. In the present study these doses of each fuel or 8% saline (SAL; 5.47 nmoles/kg) were administered immediately and at 1, 3, 6 and 23 h post-CCI. At 24 h all CCI groups and non-treated Sham injury controls were infused with [1,2 13 C] glucose for 68 min 13 C nuclear magnetic resonance (NMR) spectra were obtained from cortex + hippocampus tissues from left (injured) and right (contralateral) hemispheres. All three fuels increased lactate labeling to a similar degree in the injured hemisphere. The amount of lactate labeled via the pentose phosphate and pyruvate recycling (PPP + PR) pathway increased in CCI-SAL and was not improved by SP, EP, and GLC treatments. Oxidative metabolism, as assessed by glutamate labeling, was reduced in CCI-SAL animals. The greatest improvement in oxidative metabolism was observed in animals treated with SP and fewer improvements after EP or GLC treatments. Compared to SAL, all three fuels restored glutamate and glutamine labeling via pyruvate carboxylase (PC), suggesting improved astrocyte metabolism following fuel treatment. Only SP treatments restored the amount of [4 13 C] glutamate labeled by the PPP + PR pathway to sham levels. Milder injury effects in the contralateral hemisphere appear normalized by either SP or EP treatments, as increases in the total pool of 13 C lactate and labeling of lactate in glycolysis, or decreases in the ratio of PC/PDH labeling of glutamine, were found only for CCI-SAL and CCI-GLC groups compared to Sham. The doses of SP, EP and GLC examined in this study all enhanced lactate labeling and restored astrocyte-specific PC activity but differentially affected neuronal metabolism after CCI injury. The restoration of

  15. Quantitative autoradiography of 14C-D-glucose metabolism of normal and traumatized rat brain using micro-absorption photometry

    International Nuclear Information System (INIS)

    Bonorden, S.

    1980-01-01

    It could be shown using 14 C-glucose as energy-providing substrate for brain tissue metabolism that for bolus type application a retarded and even channelling of the substrate into the metabolic process takes place. The presence of tracer in the tissue was established using autoradiography. A linear correlation between the amount of tissue-incorporated 14 C section thickness and exposure time could be established by means of densitometric measurement of brain sections of various thicknesses, by applying various 14 C-activities and by different exposure times. From these correlations direct conclusions may be made regarding the specific activity of the tissue provided that exposure time and section thickness of the sample are known. Comparative studies between cortex and narrow and between traumatized and non-traumatized brain tissue show that the rate of metabolism in brain cortex is markedly higher than in the marrow and that 14 C-incorporation is higher in traumatized tissue than in non-traumatized tissue. Whilst the difference in rate of metabolism between brain cortex and marrow can be clearly related to the differing cell count/unit surface area for cortex and marrow, the different energy conversion rates for functionally damaged and normal brain tissue is a specific characteristic of injury. Apart from the fact that an increased 14 C-deposition is in no way indicative of an increased metabolic activity, the possibility of quantifying 14 C-tissue content provides a basis for estimating therapeutic effects e.g. in the treatment of trauma-caused brain edema. (orig.) [de

  16. The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

    Science.gov (United States)

    Kleinberger, Gernot; Brendel, Matthias; Mracsko, Eva; Wefers, Benedikt; Groeneweg, Linda; Xiang, Xianyuan; Focke, Carola; Deußing, Maximilian; Suárez-Calvet, Marc; Mazaheri, Fargol; Parhizkar, Samira; Pettkus, Nadine; Wurst, Wolfgang; Feederle, Regina; Bartenstein, Peter; Mueggler, Thomas; Arzberger, Thomas; Knuesel, Irene; Rominger, Axel; Haass, Christian

    2017-07-03

    Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p.T66M, lead to the FTD-like syndrome, but how they cause pathology is unknown. Using CRISPR/Cas9 genome editing, we generated a knock-in mouse model for the disease-associated Trem2 p.T66M mutation. Consistent with a loss-of-function mutation, we observe an intracellular accumulation of immature mutant Trem2 and reduced generation of soluble Trem2 similar to patients with the homozygous p.T66M mutation. Trem2 p.T66M knock-in mice show delayed resolution of inflammation upon in vivo lipopolysaccharide stimulation and cultured macrophages display significantly reduced phagocytic activity. Immunohistochemistry together with in vivo TSPO small animal positron emission tomography (μPET) demonstrates an age-dependent reduction in microglial activity. Surprisingly, perfusion magnetic resonance imaging and FDG-μPET imaging reveal a significant reduction in cerebral blood flow and brain glucose metabolism. Thus, we demonstrate that a TREM2 loss-of-function mutation causes brain-wide metabolic alterations pointing toward a possible function of microglia in regulating brain glucose metabolism. © 2017 The Authors.

  17. Hierarchical clustering of Alzheimer and 'normal' brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.

    2001-01-01

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element concentrations in the frontal lobe were determined for twenty six Alzheimer (15 male, 11 female) and twenty six 'normal' (8 male, 18 female) brain tissue samples. In the parietal lobe ten Alzheimer (2 male, 8 female) and ten 'normal' (8 male, 2 female) samples were taken along with ten Alzheimer (4 male, 6 female) and ten 'normal' (6 male, 4 female) from the occipital lobe. For the frontal lobe trace element concentrations were determined using proton induced X-ray emission (PIXE) analysis while in parietal and occipital regions instrumental neutron activation analysis (INAA) was used. Additionally eighteen Alzheimer (9 male, 9 female) and eighteen age matched 'normal' (8 male, 10 female) living subjects were examined using positron emission tomography (PET) in order to determine regional cerebral metabolic rates of glucose (rCMRGlu). The rCMRGlu of 36 regions of the brain was investigated including frontal, occipital and parietal lobes as in the trace element study. Hierarchical cluster analysis was applied to the trace element and glucose metabolism data to discover which variables in the resulting dendrograms displayed the most significant separation between Alzheimer and 'normal' subjects. (author)

  18. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects

    Directory of Open Access Journals (Sweden)

    Shuai Liu

    2018-01-01

    Full Text Available Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

  20. Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study.

    Science.gov (United States)

    Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

    2016-01-01

    The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects. NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software. Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (Pbrain signal transduction pathways, and the hypometabolism regions (the left superior parietal lobule, bilateral inferior parietal lobule and left fusiform gyrus) lied in dorsal attention network and visuospatial function areas. The changes of brain glucose metabolism exist in NSCLC patients prior to oncotherapy, which might be attributed to lung-cancer related visceral sympathetic activation and decrease of dorsal attention network function.

  1. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

    Science.gov (United States)

    Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

    2014-12-02

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

  2. Time series changes of MR/PET image of brain glucose metabolism in healthy subjects and alzheimer disease patients

    International Nuclear Information System (INIS)

    Tarusawa, Ayaka; Nihei, Mitsuyo; Tanaka, Mika; Fukami, Tadanori; Yuasa, Tetsuya; Wu, Jin; Kawasaki, Keiichi; Ishiwata, Kiichi; Ishii, Kenji

    2010-01-01

    Combination of morphological information by MRI and functional one by positron emission tomography (PET) was applied to quantitative evaluation of brain regional glucose metabolism in healthy subjects (HS) and Alzheimer disease patients (AD) and their individual aging changes were elucidated for ultimate purpose of computer-aided diagnosis. Subjects were: 5 AD patients (3M/2F, av. age 77.27 y), 14 ε4-carrying HS (EHS, 4M/10F, 71.3y) and 24 non-ε4-carrying HS (NEHS, 4M/20F, 70.21), where ε4 (apolipoprotein E type 4 gene allele)-carrying HS were reported to be prone to early AD and to tend to give increased brain atrophy incidence. Acquisitions of T1-weighted 3D MR and PET images were in 256 x 256 x(88-104) and x (90-100) voxels, respectively, with digitization level 16 bits, and were repeated 3 times in the time series of 21-38 months. Segmentation was performed with the MR imaging software SPM8 (Statistic Parametric Mapping: Metalab) to specify the regions of white/gray matters and cerebrospinal fluid (CSF). The binary MR and registered PET images were fused for comparison of glucose metabolism by SUVs (standardized uptake values) in gray matter of the three subject groups. Findings were: SUV in AD was markedly reduced; average time series changes per year were 0.11% in AD, -2.63% in EHS and 1.48% in NEHS; and statistical significance of the changes was between AD and NEHS, and between EHS and NEHS. Glucose metabolism by MR/PET can be thus used for a distinction of ε4-carrier and non-carrier in HS. (T.T.)

  3. Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

    Science.gov (United States)

    Song, In-Uk; Choi, Eun Kyoung; Oh, Jin Kyoung; Chung, Yong-An; Chung, Sung-Woo

    2016-01-01

    Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration. © The Foundation Acta Radiologica 2014.

  4. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  5. Early Decline in Glucose Transport and Metabolism Precedes Shift to Ketogenic System in Female Aging and Alzheimer's Mouse Brain: Implication for Bioenergetic Intervention

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R.; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3–15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6–9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  6. At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose.

    Science.gov (United States)

    Gejl, Michael; Rungby, Jørgen; Brock, Birgitte; Gjedde, Albert

    2014-08-01

    Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with both pancreatic and extrapancreatic effects. Studies of GLP-1 reveal significant effects in regions of brain tissue that regulate appetite and satiety. GLP-1 mimetics are used for the treatment of type 2 diabetes mellitus. GLP-1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging pre-clinical findings indicate a potential neuroprotective role of the peptide, for example in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten described the steady-state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose-dependent impact of GLP-1 on blood-brain glucose transfer and metabolism. This MiniReview examines the potential of GLP-1 as a molecule of interest for the understanding of brain energy metabolism and with reference to the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders. These effects can be understood only by reference to the original formulation of the Michaelis-Menten equation as applied to a chain of kinetically controlled steps. Indeed, the effects of GLP-1 receptor activation on blood-brain glucose transfer and brain metabolism of glucose depend on the glucose concentration and relative affinities of the steps both in vitro and in vivo, as in the pancreas. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  7. Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.

    Science.gov (United States)

    Nomura, Sadahiro; Fujii, Masami; Inoue, Takao; He, Yeting; Maruta, Yuichi; Koizumi, Hiroyasu; Suehiro, Eiichi; Imoto, Hirochika; Ishihara, Hideyuki; Oka, Fumiaki; Matsumoto, Mishiya; Owada, Yuji; Yamakawa, Takeshi; Suzuki, Michiyasu

    2014-05-01

    Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy. Nine patients underwent FBC at 15°C for 30 min prior to cortical resection (n = 6) or hippocampectomy (n = 3). Measurement of metabolites and CBF, as well as electrocorticography (ECoG), was performed. Epileptic discharge (ED), as observed by ECoG, disappeared in the cooling period and reappeared in the rewarming period. Glu concentrations were high during the precooling period and were reduced to 51.2% during the cooling period (p = 0.025). Glycerol levels showed a similar decrease (p = 0.028). Lactate concentration was high during the precooling period and was reduced during the cooling period (21.3% decrease; p = 0.005). Glucose and pyruvate levels were maintained throughout the procedure. Changes in CBF were parallel to those observed by ECoG. FBC reduced EDs and concentrations of Glu and glycerol. This demonstrates the neuroprotective effect of FBC. Our findings confirm that FBC is a reasonable and optimal treatment option for patients with intractable epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  8. The metabolic trinity, glucose-glycogen-lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression.

    Science.gov (United States)

    Dienel, Gerald A

    2017-01-10

    Glucose, glycogen, and lactate are traditionally identified with brain energetics, ATP turnover, and pathophysiology. However, recent studies extend their roles to include involvement in astrocytic signaling, memory consolidation, and gene expression. Emerging roles for these brain fuels and a readily-diffusible by-product are linked to differential fluxes in glycolytic and oxidative pathways, astrocytic glycogen dynamics, redox shifts, neuron-astrocyte interactions, and regulation of astrocytic activities by noradrenaline released from the locus coeruleus. Disproportionate utilization of carbohydrate compared with oxygen during brain activation is influenced by catecholamines, but its physiological basis is not understood and its magnitude may be affected by technical aspects of metabolite assays. Memory consolidation and gene expression are impaired by glycogenolysis blockade, and prevention of these deficits by injection of abnormally-high concentrations of lactate was interpreted as a requirement for astrocyte-to-neuron lactate shuttling in memory and gene expression. However, lactate transport was not measured and evidence for presumed shuttling is not compelling. In fact, high levels of lactate used to preserve memory consolidation and induce gene expression are sufficient to shut down neuronal firing via the HCAR1 receptor. In contrast, low lactate levels activate a receptor in locus coeruleus that stimulates noradrenaline release that may activate astrocytes throughout brain. Physiological relevance of exogenous concentrations of lactate used to mimic and evaluate metabolic, molecular, and behavioral effects of lactate requires close correspondence with the normal lactate levels, the biochemical and cellular sources and sinks, and specificity of lactate delivery to target cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Temporal Changes in Cortical and Hippocampal Expression of Genes Important for Brain Glucose Metabolism Following Controlled Cortical Impact Injury in Mice

    Directory of Open Access Journals (Sweden)

    June Zhou

    2017-09-01

    Full Text Available Traumatic brain injury (TBI causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group underwent sham or unilateral controlled cortical impact (CCI injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. Expressions of several genes important for brain glucose utilization were determined by qRT-PCR. In results, (1 mRNA levels of three key enzymes in glucose metabolism [hexo kinase (HK 1, pyruvate kinase, and pyruvate dehydrogenase (PDH] were all increased 6 h after injury in the contralateral cortex, followed by decreases at subsequent times in the ipsilateral cortex and hippocampus; (2 capillary glucose transporter Glut-1 mRNA increased, while neuronal glucose transporter Glut-3 mRNA decreased, at various times in the ipsilateral cortex and hippocampus; (3 astrocyte lactate transporter MCT-1 mRNA increased, whereas neuronal lactate transporter MCT-2 mRNA decreased in the ipsilateral cortex and hippocampus; (4 HK2 (an isoform of hexokinase expression increased at all time points in the ipsilateral cortex and hippocampus. GPR81 (lactate receptor mRNA increased at various time points in the ipsilateral cortex and hippocampus. These temporal alterations in gene expression corresponded closely to the patterns of impaired brain glucose utilization reported in both TBI patients and experimental TBI rodents. The observed changes in hippocampal gene expression were delayed and prolonged, when compared with those in the cortex. The patterns of alterations were specific

  10. Tritiated 2-deoxy-D-glucose: a high-resolution marker for autoradiographic localization of brain metabolism

    International Nuclear Information System (INIS)

    Hammer, R.P. Jr.; Herkenham, M.

    1984-01-01

    The technique for autoradiographic localization of 2-deoxy-D-glucose (2DG) uptake has become a useful method for observing alterations of functional brain activity resulting from experimental manipulation. Autoradiographic resolution is improved using tritiated ([3H]) rather than carbon-14 ([14C)]2DG, due to the lower energy and shorter path of tritium emissions. In addition, lower 2DG uptake by white matter relative to gray matter is exaggerated in the [3H]2DG autoradiographs due to the greater absorption of tritium emissions by lipids. Using [3H]2DG, it is possible to observe differential metabolic labeling in various individual nuclei or portions of nuclei that is unresolvable using [14C]2DG in the awake, normal animal. Heterogeneous patterns of 2DG uptake seen only with [3H]2DG are found in the nucleus accumbens, the anterior portion of the basolateral nucleus of the amygdala, specific nuclei of the inferior olivary complex, various hypothalamic regions, and a region straddling the border of the medial and lateral habenular nuclei. The lamination of differential 2DG uptake in the hippocampus is better localized using [3H]2DG. Autoradiographic resolution of labeled 2DG is further improved when the brain is perfused prior to frozen sectioning, due perhaps to selective fixation and retention of intracellular labeled 2-deoxy-glycogen. A series of [3H]2DG autoradiographs are presented together with views of the Nissl-stained sections that produced the autoradiographs

  11. Comments on "Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Mental Retardation and Down Syndrome."

    Science.gov (United States)

    Willerman, Lee; Schultz, Robert T.

    1995-01-01

    The relationship between mental retardation and brain size is discussed. Research suggests that a common path for many otherwise idiopathic mild retardation cases (genetic or environmental) could be small brain size, indicating reduced information processing capacity. Suggestions are made for further research on neuron number. (SLD)

  12. Evidence for brain glucose dysregulation in Alzheimer's disease.

    Science.gov (United States)

    An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

    2018-03-01

    It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

  13. Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [18F]FDG PET Study

    Directory of Open Access Journals (Sweden)

    Akie Inami

    2017-01-01

    Full Text Available Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET. Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT intervention (treatment condition and once after resting (control condition. We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity, and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity.

  14. The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

    OpenAIRE

    Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

    2012-01-01

    The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s dis...

  15. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Park, Kwang Suk [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea); Seoul National University College of Medicine, Department of Biomedical Engineering, Seoul (Korea); Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul [Seoul National University College of Medicine, Department of Otolaryngology, Head and Neck Surgery, Seoul (Korea); Lee, Dong Soo; Jeong, Jae Min [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea)

    2005-06-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1-{sup 14}C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in

  16. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Park, Kwang Suk; Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul; Lee, Dong Soo; Jeong, Jae Min

    2005-01-01

    Animal models of cortical deafness are essential for investigation of the cerebral glucose metabolism in congenital or prelingual deafness. Autoradiographic imaging is mainly used to assess the cerebral glucose metabolism in rodents. In this study, procedures for the 3D voxel-based statistical analysis of autoradiographic data were established to enable investigations of the within-modal and cross-modal plasticity through entire areas of the brain of sensory-deprived animals without lumping together heterogeneous subregions within each brain structure into a large region of interest. Thirteen 2-[1- 14 C]-deoxy-D-glucose autoradiographic images were acquired from six deaf and seven age-matched normal rats (age 6-10 weeks). The deafness was induced by surgical ablation. For the 3D voxel-based statistical analysis, brain slices were extracted semiautomatically from the autoradiographic images, which contained the coronal sections of the brain, and were stacked into 3D volume data. Using principal axes matching and mutual information maximization algorithms, the adjacent coronal sections were co-registered using a rigid body transformation, and all sections were realigned to the first section. A study-specific template was composed and the realigned images were spatially normalized onto the template. Following count normalization, voxel-wise t tests were performed to reveal the areas with significant differences in cerebral glucose metabolism between the deaf and the control rats. Continuous and clear edges were detected in each image after registration between the coronal sections, and the internal and external landmarks extracted from the spatially normalized images were well matched, demonstrating the reliability of the spatial processing procedures. Voxel-wise t tests showed that the glucose metabolism in the bilateral auditory cortices of the deaf rats was significantly (P<0.001) lower than that in the controls. There was no significantly reduced metabolism in any

  17. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    International Nuclear Information System (INIS)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki

    2009-01-01

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6±18.2 years; 46 females, mean age 40.6±19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  18. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki (Dept. of Nuclear Medicine, Pusan National Univ. Hospital, Busan (Korea); Medical Research Institute, Pusan National Univ., Busan (Korea)). e-mail: growthkim@daum.net/growthkim@pusan.ac.kr)

    2009-12-15

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6+-18.2 years; 46 females, mean age 40.6+-19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  19. Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

    International Nuclear Information System (INIS)

    Mosconi, Lisa; Rusinek, Henry; De Santi, Susan; Li, Yi; Tsui, Wai H.; De Leon, Mony J.; Wang, Gene-Jack; Fowler, Joanna; Pupi, Alberto

    2007-01-01

    To examine CMRglc measures and corresponding glucose transport (K 1 and k 2 ) and phosphorylation (k 3 ) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 ± 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 ± 9 years, three females, median MMSE 30). Absolute CMRglc (μmol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k 3 reductions were found in the hippocampus, PCC and amygdala. K 1 reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability. (orig.)

  20. Glucose transport in brain - effect of inflammation.

    Science.gov (United States)

    Jurcovicova, J

    2014-01-01

    Glucose is transported across the cell membrane by specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient. In the brain, both types of transporters are present with different function, affinity, capacity, and tissue distribution. GLUT1 occurs in brain in two isoforms. The more glycosylated GLUT1 is produced in brain microvasculature and ensures glucose transport across the blood brain barrier (BBB). The less glycosylated form is localized in astrocytic end-feet and cell bodies and is not present in axons, neuronal synapses or microglia. Glucose transported to astrocytes by GLUT1 is metabolized to lactate serving to neurons as energy source. Proinflammatory cytokine interleukin (IL)-1β upregulates GLUT1 in endothelial cells and astrocytes, whereas it induces neuronal death in neuronal cell culture. GLUT2 is present in hypothalamic neurons and serves as a glucose sensor in regulation of food intake. In neurons of the hippocampus, GLUT2 is supposed to regulate synaptic activity and neurotransmitter release. GLUT3 is the most abundant glucose transporter in the brain having five times higher transport capacity than GLUT1. It is present in neuropil, mostly in axons and dendrites. Its density and distribution correlate well with the local cerebral glucose demands. GLUT5 is predominantly fructose transporter. In brain, GLUT5 is the only hexose transporter in microglia, whose regulation is not yet clear. It is not present in neurons. GLUT4 and GLUT8 are insulin-regulated glucose transporters in neuronal cell bodies in the cortex and cerebellum, but mainly in the hippocampus and amygdala, where they maintain hippocampus-dependent cognitive functions. Insulin translocates GLUT4 from cytosol to plasma

  1. Glucose metabolism-weighted imaging with chemical exchange-sensitive MRI of 2-deoxyglucose (2DG) in brain: Sensitivity and biological sources.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2016-12-01

    Recent proof-of-principle studies have demonstrated the feasibility of measuring the uptake and metabolism of non-labeled 2-deoxy-D-glucose (2DG) by a chemical exchange-sensitive spin-lock (CESL) MRI approach. In order to gain better understanding of this new approach, we performed dynamic in vivo CESL MRI on healthy rat brains with an intravenous injection of 2DG under various conditions at 9.4T. For three 2DG doses of 0.25, 0.5 and 1g/kg, we found that 2DG-CESL signals increased linearly with injection dose at the initial (40min) suggesting time-dependent differential weightings of 2DG transport and metabolism. Remaining 2DG-CESL studies were performed with 0.25g/kg 2DG. Since a higher isoflurane level reduces glucose metabolism and increases blood flow, 2DG-CESL was measured under 0.5%, 1.5% and 2.2% isoflurane. The 2DG-CESL signal was reduced at higher isoflurane levels correlating well with the 2DG phosphorylation in the intracellular space. To detect regional heterogeneities of glucose metabolism, 2DG-CESL with 0.33×0.33×1.50mm 3 resolution was obtained, which indeed showed a higher response in the cortex compared to the corpus callosum. Lastly, unlike CESL MRI with the injection of non-transportable mannitol, the 2DG-CESL response decreased with an increased spin-lock pulse power confirming that 2DG-CESL is dominated by chemical exchange processes in the extravascular space. Taken together, our results showed that 2DG-CESL MRI signals mainly indicate glucose transport and metabolism and may be a useful biomarker for metabolic studies of normal and diseased brains. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin

    International Nuclear Information System (INIS)

    Kasalicky, J.; Konopkova, M.; Melichar, F.

    2001-01-01

    To study the effect of lipid depressing drugs on 18 FDG myocardial concentration. The changes of 18 FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18 FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal 18 FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before 18 FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18 FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18 FDG). The animals were killed 45 minutes following 18 FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18 FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18 FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18 FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18 FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18 FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium. (author)

  3. Measuring brain glucose phosphorylation with labeled glucose

    International Nuclear Information System (INIS)

    Brondsted, H.E.; Gjedde, A.

    1988-01-01

    This study tested whether glucose labeled at the C-6 position generates metabolites that leave brain so rapidly that C-6-labeled glucose cannot be used to measure brain glucose phosphorylation (CMRGlc). In pentobarbital-anesthetized rats, the parietal cortex uptake of [ 14 C]glucose labeled in the C-6 position was followed for times ranging from 10 s to 60 min. We subtracted the observed radioactivity from the radioactivity expected with no loss of labeled metabolites from brain by extrapolation of glucose uptake in an initial period when loss was negligible. The observed radioactivity was a monoexponentially declining function of the total radioactivity expected in the absence of metabolite loss. The constant of decline was 0.0077.min-1 for parietal cortex. Metabolites were lost from the beginning of the experiment. However, with correction for the loss of labeled metabolites, it was possible to determine an average CMRGlc between 4 and 60 min of circulation of 64 +/- 4 (SE; n = 49) mumol.hg-1.min-1

  4. Sugar for the brain: the role of glucose in physiological and pathological brain function.

    Science.gov (United States)

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

    2013-10-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

    Science.gov (United States)

    Jeong, Hyeonseok S; Choi, Eun Kyoung; Song, In-Uk; Chung, Yong-An; Park, Jong-Sik; Oh, Jin Kyoung

    2017-01-01

    In preparation for 131 I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18 F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18 F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

  6. Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by positron autoradiography

    International Nuclear Information System (INIS)

    Omata, N.; Fujibayashi, Y.; Waki, A.; Sadato, N.; Yano, R.; Yoshimoto, M.; Yonekura, Y.; Murata, T.; Yoshida, S.

    1999-01-01

    Fresh rat brain slices were incubated with 2-deoxy-2-[ 18 F]-fluoro-D-glucose ([ 18 F]FDG) in oxygenated Krebs-Ringer solution at 36 degree C, and serial two-dimensional time-resolved images of [ 18 F]FDG uptake were obtained from these specimens on imaging plates. The fractional rate constant (= k3*) of [ 18 F]FDG proportional to the cerebral glucose metabolic rate (CMRglc) was evaluated by applying the Gjedde-Patlak graphical method to the image data. With hypoxia loading (oxygen deprivation) or glucose metabolism inhibitors acting on oxidative phosphorylation, the k3* value increased dramatically suggesting enhanced glycolysis. After relieving hypoxia ≤10-min, the k3* value returned to the pre-loading level. In contrast, with ≥20-min hypoxia only partial or no recovery was observed, indicating that irreversible neuronal damage had been induced. However, after loading with tetrodotoxin (TTX), the k3* value also decreased but returned to the pre-loading level even after 70-min TTX-loading, reflecting a transient inhibition of neuronal activity. This technique provides a new means of quantifying dynamic changes in the regional CMRglc in living brain slices in response to various interventions such as hypoxia and neurotoxic chemical-loading as well as determining the viability and prognosis of brain tissues. (author)

  7. Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study.

    Science.gov (United States)

    Courchesne-Loyer, Alexandre; Croteau, Etienne; Castellano, Christian-Alexandre; St-Pierre, Valérie; Hennebelle, Marie; Cunnane, Stephen C

    2017-07-01

    Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11 C-AcAc and 18 F-fluorodeoxyglucose ( 18 F-FDG), respectively. During the KD, plasma ketones increased 8-fold ( p = 0.005) while plasma glucose decreased by 24% ( p = 0.005). CMRa increased 6-fold ( p = 0.005), whereas CMRglc decreased by 20% ( p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p < 0.0001). After four days on the KD, CMRa represented 17% of whole brain energy requirements in healthy adults with a 2-fold difference across brain regions (12-24%). The CMR of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements or approximately double the CMRa. Whether increased ketone availability raises CMR of ketones to the same extent in older people as observed here or in conditions in which chronic brain glucose hypometabolism is present remains to be determined.

  8. Dementia with impaired glucose metabolism in late onset metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Johannsen, P.; Ehlers, L.; Hansen, Hans Jacob

    2001-01-01

    and attention deficits with a slow psychomotor speed. MR brain imaging displayed confluent hyperintensities of periventricular and subcortical white matter. Low levels of arylsulfatase A confirmed the diagnosis. Impaired cortical glucose metabolism especially of the medial temporal and frontal cortices...... was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism....

  9. Is cerebral glucose metabolism related to blood–brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?

    Science.gov (United States)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Francesco, Ursini; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Torniolo, Sofia; Di Pietro, Barbara; Motta, Caterina; Schillaci, Orazio

    2016-01-01

    Abstract The aim of this study was to investigate the relationships between blood–brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(18F) fluoro-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before 18F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and 18F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects. PMID:27631200

  10. Brain glucose overexposure and lack of acute metabolic flexibility in obesity and type 2 diabetes: a PET-[18F]FDG study in Zucker and ZDF rats

    OpenAIRE

    Liistro, Tiziana; Guiducci, Letizia; Burchielli, Silvia; Panetta, Daniele; Belcari, Nicola; Pardini, Silvia; Guerra, Alberto Del; Salvadori, Piero A; Iozzo, Patricia

    2010-01-01

    Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with 18F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and ...

  11. A positron emission tomography analysis of glucose metabolism in Alzheimer's disease brain using [18F] fluorodeoxyglucose. A parallel study with elemental concentrations

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.; Stedman, J.D.

    2000-01-01

    Alzheimer's disease (AD) is a debilitating form of dementia which leads to impaired memory, thinking and behavior. Elemental concentrations between 'normal' and AD subjects as well as the hemispherical differences within the brain were examined. Tissue samples from both hemispheres of the frontal lobe in both AD and normal subjects were examined for their trace element concentrations using PIXE and RBS analyses. Elemental concentrations were seen to differ between AD and normal brain tissue samples. While in the normal group concentrations were found to be significantly higher in the right hemisphere than in the left the converse was tru in AD. A change in elemental concentrations may indicate possible alterations in the function of the blood brain barrier. This was examined by determining regional cerebral metabolic rates of glucose (rCMRGlu) using the in vivo technique of positron emission tomography (PET). Again variations between both hemispheres and between AD and normal were found. (author)

  12. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

    Science.gov (United States)

    Wegner, Florian; Wilke, Florian; Raab, Peter; Tayeb, Said Ben; Boeck, Anna-Lena; Haense, Cathleen; Trebst, Corinna; Voss, Elke; Schrader, Christoph; Logemann, Frank; Ahrens, Jörg; Leffler, Andreas; Rodriguez-Raecke, Rea; Dengler, Reinhard; Geworski, Lilli; Bengel, Frank M; Berding, Georg; Stangel, Martin; Nabavi, Elham

    2014-06-20

    Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

  13. Parsing glucose entry into the brain: novel findings obtained with enzyme-based glucose biosensors.

    Science.gov (United States)

    Kiyatkin, Eugene A; Wakabayashi, Ken T

    2015-01-21

    Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between "active" and "passive" glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the "neuronal" hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism.

  14. Regional registration of [6-14C]glucose metabolism during brain activation of α-syntrophin knockout mice

    Science.gov (United States)

    Cruz, Nancy F.; Ball, Kelly K.; Froehner, Stanley C.; Adams, Marvin E.; Dienel, Gerald A.

    2013-01-01

    α-Syntrophin is a component of the dystrophin scaffold-protein complex that serves as an adaptor for recruitment of key proteins to the cytoplasmic side of plasma membranes. α-Syntrophin knockout (KO) causes loss of the polarized localization of aquaporin4 (AQP4) at astrocytic endfeet and interferes with water and K+ homeostasis. During brain activation, release of ions and metabolites from endfeet is anticipated to increase perivascular fluid osmolarity, AQP4-mediated osmotic water flow from endfeet, and metabolite washout from brain. This study tests the hypothesis that reduced levels of endfoot AQP4 increase retention of [14C]metabolites during sensory stimulation. Conscious KO and wildtype mice were pulse-labeled with [6-14C]glucose during unilateral acoustic stimulation or bilateral acoustic plus whisker stimulation, and label retention was assayed by computer-assisted brain imaging or analysis of [14C]metabolites in extracts, respectively. High-resolution autoradiographic assays detected a 17% side-to-side difference (P<0.05) in inferior colliculus of KO mice, not wildtype mice. However, there were no labeling differences between KO and wildtype mice for five major HPLC fractions from four dissected regions, presumably due to insufficient anatomical resolution. The results suggest a role for AQP4-mediated water flow in support of washout of metabolites, and underscore the need for greater understanding of astrocytic water and metabolite fluxes. PMID:23346911

  15. Human ApoE Isoforms Differentially Modulate Glucose and Amyloid Metabolic Pathways in Female Brain: Evidence of the Mechanism of Neuroprotection by ApoE2 and Implications for Alzheimer's Disease Prevention and Early Intervention.

    Science.gov (United States)

    Keeney, Jeriel Thomas-Richard; Ibrahimi, Shaher; Zhao, Liqin

    2015-01-01

    Three major genetic isoforms of apolipoprotein E (ApoE), ApoE2, ApoE3, and ApoE4, exist in humans and lead to differences in susceptibility to Alzheimer's disease (AD). This study investigated the impact of human ApoE isoforms on brain metabolic pathways involved in glucose utilization and amyloid-β (Aβ) degradation, two major areas that are significantly perturbed in preclinical AD. Hippocampal RNA samples from middle-aged female mice with targeted human ApoE2, ApoE3, and ApoE4 gene replacement were comparatively analyzed with a qRT-PCR custom array for the expression of 85 genes involved in insulin/insulin-like growth factor (Igf) signaling. Consistent with its protective role against AD, ApoE2 brain exhibited the most metabolically robust profile among the three ApoE genotypes. When compared to ApoE2 brain, both ApoE3 and ApoE4 brains exhibited markedly reduced levels of Igf1, insulin receptor substrates (Irs), and facilitated glucose transporter 4 (Glut4), indicating reduced glucose uptake. Additionally, ApoE4 brain exhibited significantly decreased Pparg and insulin-degrading enzyme (Ide), indicating further compromised glucose metabolism and Aβ dysregulation associated with ApoE4. Protein analysis showed significantly decreased Igf1, Irs, and Glut4 in ApoE3 brain, and Igf1, Irs, Glut4, Pparg, and Ide in ApoE4 brain compared to ApoE2 brain. These data provide the first documented evidence that human ApoE isoforms differentially affect brain insulin/Igf signaling and downstream glucose and amyloid metabolic pathways, illustrating a potential mechanism for their differential risk in AD. A therapeutic strategy that enhances brain insulin/Igf1 signaling activity to a more robust ApoE2-like phenotype favoring both energy production and amyloid homeostasis holds promise for AD prevention and early intervention.

  16. Glucosensing in the gastrointestinal tract: Impact on glucose metabolism

    Science.gov (United States)

    Fournel, Audren; Marlin, Alysson; Abot, Anne; Pasquio, Charles; Cirillo, Carla; Cani, Patrice D.

    2016-01-01

    The gastrointestinal tract is an important interface of exchange between ingested food and the body. Glucose is one of the major dietary sources of energy. All along the gastrointestinal tube, e.g., the oral cavity, small intestine, pancreas, and portal vein, specialized cells referred to as glucosensors detect variations in glucose levels. In response to this glucose detection, these cells send hormonal and neuronal messages to tissues involved in glucose metabolism to regulate glycemia. The gastrointestinal tract continuously communicates with the brain, especially with the hypothalamus, via the gut-brain axis. It is now well established that the cross talk between the gut and the brain is of crucial importance in the control of glucose homeostasis. In addition to receiving glucosensing information from the gut, the hypothalamus may also directly sense glucose. Indeed, the hypothalamus contains glucose-sensitive cells that regulate glucose homeostasis by sending signals to peripheral tissues via the autonomous nervous system. This review summarizes the mechanisms by which glucosensors along the gastrointestinal tract detect glucose, as well as the results of such detection in the whole body, including the hypothalamus. We also highlight how disturbances in the glucosensing process may lead to metabolic disorders such as type 2 diabetes. A better understanding of the pathways regulating glucose homeostasis will further facilitate the development of novel therapeutic strategies for the treatment of metabolic diseases. PMID:26939867

  17. Glucosensing in the gastrointestinal tract: Impact on glucose metabolism.

    Science.gov (United States)

    Fournel, Audren; Marlin, Alysson; Abot, Anne; Pasquio, Charles; Cirillo, Carla; Cani, Patrice D; Knauf, Claude

    2016-05-01

    The gastrointestinal tract is an important interface of exchange between ingested food and the body. Glucose is one of the major dietary sources of energy. All along the gastrointestinal tube, e.g., the oral cavity, small intestine, pancreas, and portal vein, specialized cells referred to as glucosensors detect variations in glucose levels. In response to this glucose detection, these cells send hormonal and neuronal messages to tissues involved in glucose metabolism to regulate glycemia. The gastrointestinal tract continuously communicates with the brain, especially with the hypothalamus, via the gut-brain axis. It is now well established that the cross talk between the gut and the brain is of crucial importance in the control of glucose homeostasis. In addition to receiving glucosensing information from the gut, the hypothalamus may also directly sense glucose. Indeed, the hypothalamus contains glucose-sensitive cells that regulate glucose homeostasis by sending signals to peripheral tissues via the autonomous nervous system. This review summarizes the mechanisms by which glucosensors along the gastrointestinal tract detect glucose, as well as the results of such detection in the whole body, including the hypothalamus. We also highlight how disturbances in the glucosensing process may lead to metabolic disorders such as type 2 diabetes. A better understanding of the pathways regulating glucose homeostasis will further facilitate the development of novel therapeutic strategies for the treatment of metabolic diseases. Copyright © 2016 the American Physiological Society.

  18. Ketosis proportionately spares glucose utilization in brain.

    Science.gov (United States)

    Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

    2013-08-01

    The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.

  19. Sensing of glucose in the brain.

    Science.gov (United States)

    Thorens, Bernard

    2012-01-01

    The brain, and in particular the hypothalamus and brainstem, have been recognized for decades as important centers for the homeostatic control of feeding, energy expenditure, and glucose homeostasis. These structures contain neurons and neuronal circuits that may be directly or indirectly activated or inhibited by glucose, lipids, or amino acids. The detection by neurons of these nutrient cues may become deregulated, and possibly cause metabolic diseases such as obesity and diabetes. Thus, there is a major interest in identifying these neurons, how they respond to nutrients, the neuronal circuits they form, and the physiological function they control. Here I will review some aspects of glucose sensing by the brain. The brain is responsive to both hyperglycemia and hypoglycemia, and the glucose sensing cells involved are distributed in several anatomical sites that are connected to each other. These eventually control the activity of the sympathetic or parasympathetic nervous system, which regulates the function of peripheral organs such as liver, white and brown fat, muscle, and pancreatic islets alpha and beta cells. There is now evidence for an extreme diversity in the sensing mechanisms used, and these will be reviewed.

  20. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    OpenAIRE

    Kleinridders, Andr?; Ferris, Heather A.; Cai, Weikang; Kahn, C. Ronald

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in t...

  1. Sex steroids and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Carolyn A Allan

    2014-04-01

    Full Text Available Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

  2. Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

    OpenAIRE

    Gejl, Michael; Lerche, Susanne; Egefjord, L?rke; Brock, Birgitte; M?ller, Niels; Vang, Kim; Rodell, Anders B.; Bibby, Bo M.; Holst, Jens J.; Rungby, J?rgen; Gjedde, Albert

    2013-01-01

    In hyperglycemia, glucagon-like peptide-1 (GLP-1) lowers brain glucose concentration together with increased net blood-brain clearance and brain metabolism, but it is not known whether this effect depends on the prevailing plasma glucose (PG) concentration. In hypoglycemia, glucose depletion potentially impairs brain function. Here, we test the hypothesis that GLP-1 exacerbates the effect of hypoglycemia. To test the hypothesis, we determined glucose transport and consumption rates in seven h...

  3. Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

    2003-01-01

    a median recurrence free survival of 16 years by MRI and Positron Emission Tomography using the glucose analog 2-18F-fluoro-2-deoxy-D-glucose (18FDG). Three patients were not analyzed further due to diffuse cerebral atrophy, which might be related to previous hydrocephalus. Twenty-one patients were...

  4. [Glucose homeostasis and gut-brain connection].

    Science.gov (United States)

    De Vadder, Filipe; Mithieux, Gilles

    2015-02-01

    Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

  5. Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

    Directory of Open Access Journals (Sweden)

    Xue-Yuan Li

    2016-10-01

    Full Text Available Alzheimer’s disease (AD is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1 transgenic (Tg mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr. Morris water maze (MWM was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD. By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD. Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.

  6. Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

    Science.gov (United States)

    Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi

    2016-10-18

    Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18 F-labed fluorodeoxyglucose ( 18 F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

  7. A mathematical model of brain glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  8. Simultaneous measurement of glucose transport and utilization in the human brain

    OpenAIRE

    Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.; Öz, Gülin

    2011-01-01

    Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose tra...

  9. Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study.

    Science.gov (United States)

    Jeong, H S; Park, J S; Song, I U; Chung, Y A; Rhie, S J

    2017-01-01

    Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. Clinical evaluation, comprehensive neuropsychological test, and 18 F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: -0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (β = 0.43, P = 0.02). Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Steady-state cerebral glucose concentrations and transport in the human brain

    OpenAIRE

    Gruetter, R.; Ugurbil, K.; Seaquist, E. R.

    1998-01-01

    Understanding the mechanism of brain glucose transport across the blood- brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport nave been generally described using standard Michaelis-Menten kinetics. These models predict that the steady- state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Michaelis-Menten constant for half-maximal transport, K(t). In experiments wh...

  11. Metabolism of glucose in brain of patients with Parkinson's disease. Studies on /sup 11/C-glucose metabolism in the striatum and cerebral cortex during medication or interruption of medication by positron emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki

    1984-12-01

    We examined /sup 11/C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with /sup 11/C-Glucose (per os). /sup 11/C-Glucose was prepared from /sup 11/CO/sub 2/ by photosynthesis. 1) No significant difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author).

  12. Hierarchical clustering of Alzheimer and "normal" brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    NARCIS (Netherlands)

    Cutts, DA; Spyrou, NM; Maguire, RP; Leenders, KL

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element

  13. Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.

    Science.gov (United States)

    Yang, Feng-Yi; Chang, Wen-Yuan; Chen, Jyh-Cheng; Lee, Lin-Chien; Hung, Yi-Shun

    2014-04-15

    The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Comparing amyloid-β deposition, neuroinflammation, glucose metabolism, and mitochondrial complex I activity in brain: a PET study in aged monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Tsukada, Hideo; Nishiyama, Shingo; Ohba, Hiroyuki; Kanazawa, Masakatsu; Kakiuchi, Takeharu; Harada, Norihiro [Hamamatsu Photonics K.K., Central Research Laboratory, Shizuoka (Japan)

    2014-11-15

    The aim of the present study was to compare amyloid-β (Aβ) deposition, translocator protein (TSPO) activity, regional cerebral metabolic rate of glucose (rCMRglc), and mitochondrial complex I (MC-I) activity in the brain of aged monkeys. PET scans with {sup 11}C-PIB (Aβ), {sup 18}F-BCPP-EF (MC-I), {sup 11}C-DPA-713 (TSPO), and {sup 18}F-FDG (rCMRglc) were performed in aged monkeys (Macaca mulatta) in the conscious state and under isoflurane anaesthesia. {sup 11}C-PIB binding to Aβ and {sup 11}C-DPA-713 binding to TSPO were evaluated in terms of standard uptake values (SUV). The total volume of distribution (V{sub T}) of {sup 18}F-BCPP-EF and rCMRglc with {sup 18}F-FDG were calculated using arterial blood sampling. Isoflurane did not affect MC-I activity measured in terms of {sup 18}F-BCPP-EF uptake in living brain. There was a significant negative correlation between {sup 18}F-BCPP-EF binding (V{sub T}) and {sup 11}C-PIB uptake (SUVR), and there was a significant positive correlation between {sup 11}C-DPA-713 uptake (SUV) and {sup 11}C-PIB uptake. In contrast, there was no significant correlation between rCMRglc ratio and {sup 11}C-PIB uptake. {sup 18}F-BCPP-EF could be a potential PET probe for quantitative imaging of impaired MC-I activity that is correlated with Aβ deposition in the living brain. (orig.)

  15. In vivo measurements of brain glucose transport using the reversible michaelis-menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia

    OpenAIRE

    Choi, I.-Y.; Lee, S.-P.; Kim, S.-G.; Gruetter, R.

    2001-01-01

    Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood-brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in α-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma ...

  16. Brain glucose sensing in homeostatic and hedonic regulation.

    Science.gov (United States)

    Steinbusch, Laura; Labouèbe, Gwenaël; Thorens, Bernard

    2015-09-01

    Glucose homeostasis as well as homeostatic and hedonic control of feeding is regulated by hormonal, neuronal, and nutrient-related cues. Glucose, besides its role as a source of metabolic energy, is an important signal controlling hormone secretion and neuronal activity, hence contributing to whole-body metabolic integration in coordination with feeding control. Brain glucose sensing plays a key, but insufficiently explored, role in these metabolic and behavioral controls, which when deregulated may contribute to the development of obesity and diabetes. The recent introduction of innovative transgenic, pharmacogenetic, and optogenetic techniques allows unprecedented analysis of the complexity of central glucose sensing at the molecular, cellular, and neuronal circuit levels, which will lead to a new understanding of the pathogenesis of metabolic diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Blood-Brain Glucose Transfer in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, Michael; Brock, Birgitte; Egefjord, Lærke

    2017-01-01

    There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral...... metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD...

  18. In vivo 13C MRS in the mouse brain at 14.1 Tesla and metabolic flux quantification under infusion of [1,6-13C2]glucose.

    Science.gov (United States)

    Lai, Marta; Lanz, Bernard; Poitry-Yamate, Carole; Romero, Jackeline F; Berset, Corina M; Cudalbu, Cristina; Gruetter, Rolf

    2017-01-01

    In vivo 13 C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing 13 C-labeled glucose. Metabolic flux analysis of 13 C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, 13 C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6- 13 C 2 ]glucose for up to 5 h. 13 C incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were detected dynamically and fitted to a two-compartment model: flux estimation of neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in astrocytes (V g  = 0.16 ± 0.03 µmol/g/min) and neurons (V TCA n  = 0.56 ± 0.03 µmol/g/min), pyruvate carboxylase activity (V PC  = 0.041 ± 0.003 µmol/g/min) and neurotransmission rate (V NT  = 0.084 ± 0.008 µmol/g/min), resulting in a cerebral metabolic rate of glucose (CMR glc ) of 0.38 ± 0.02 µmol/g/min, in excellent agreement with that determined with concomitant 18 F-fluorodeoxyglucose positron emission tomography ( 18 FDG PET).We conclude that modeling of neuron-glial metabolism in vivo is accessible in the mouse brain from 13 C direct detection with an unprecedented spatial resolution under [1,6- 13 C 2 ]glucose infusion.

  19. The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

    Science.gov (United States)

    Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

    2012-01-01

    The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain. PMID:23202918

  20. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    OpenAIRE

    Park, Weon Wook; Suh, Kuen Tak; Kim, Jeung Il; Ku, Ja Gyung; Lee, Hong Seok; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Lee, Jung Sub

    2008-01-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with ...

  1. Glucose metabolism in diabetic blood vessels

    International Nuclear Information System (INIS)

    Brown, B.J.; Crass, M.F. III

    1986-01-01

    Since glycolysis appears to be coupled to active ion transport in vascular smooth muscle, alterations in glucose metabolism may contribute to cellular dysfunction and angiopathy in diabetes. Uptake and utilization of glucose were studied in perfused blood vessels in which pulsatile flow and perfusion pressure were similar to those measured directly in vivo. Thoracic aortae isolated from 8-wk alloxan diabetic (D) and nondiabetic control rabbits were cannulated, tethered, and perfused with oxygenated buffer containing 7 or 25 mM glucose and tracer amounts of glucose-U -14 C. Norepinephrine (NE) (10 -6 M) and/or insulin (I) (150 μU/ml) and albumin (0.2%) were added. NE-induced tension development increased glucose uptake 39% and 14 CO 2 and lactate production 2.3-fold. With 7 mM glucose, marked decreases in glucose uptake (74%), 14 CO 2 (68%), lactate (30%), total tissue glycogen (75%), and tissue phospholipids (70%) were observed in D. Addition of I or elevation of exogenous glucose to 25 mM normalized glucose uptake, but had differential effects on the pattern of substrate utilization. Thus, in D, there was a marked depression of vascular glucose metabolism that was partially reversed by addition of low concentrations of insulin or D levels of glucose

  2. Glucose metabolism in lactating reindeer

    Energy Technology Data Exchange (ETDEWEB)

    White, R G; Luick, J R

    1976-01-01

    Changes in glucose synthesis during the lactation cycle were estimated in pen-fed and grazing reindeer. The pool size, space, transfer rate, and irreversible loss of glucose were determined using simultaneous injections of (2-/sup 3/H)glucose and primed infusions of (U-/sup 14/C)glucose in reindeer lactating for 1-2, 4-5, 8-9, and 12-16 weeks. Glucose transfer rate and irreversible loss were higher during early to midlactation than at other times of the year; maximum estimates were at 8-9 week postpartum (July), and a decline was noted at 12-16 weeks (August). During the first 1-2 weeks in pen-fed and 4-5 weeks in grazing reindeer, glucose transfer rate and irreversible loss were almost twice the values reported for reindeer at maintenance. No difference in the irreversible loss of glucose was noted between lactating and non-lactating reindeer at 18-20 weeks postpartum (September), and there is evidence that this may occur as early as 12-16 weeks postpartum. No significant trend was noted in the glucose space throughout lactation; however, a significant increase in plasma glucose concentration and pool size was noted when glucose synthesis was highest (8-9 weeks postpartum). Glucose turnover time was consistently faster (78-88 min) in lactating than in non-lactating reindeer (107-140 min). Reindeer used a smaller proportion of plasma glucose-C for lactose synthesis than did other domestic species. This probably results from the low lactose content of reindeer milk and the relatively low rate of milk secretion. (auth)

  3. Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Mosconi, Lisa; Rusinek, Henry; De Santi, Susan; Li, Yi [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Tsui, Wai H.; De Leon, Mony J. [New York University School of Medicine, Center for Brain Health, MHL 400, Department of Psychiatry, New York, NY (United States); Nathan Kline Institute, Orangeburg, NY (United States); Wang, Gene-Jack; Fowler, Joanna [Brookhaven National Laboratory, Upton, NY (United States); Pupi, Alberto [University of Florence, Department of Clinical Pathophysiology, Nuclear Medicine Unit, Florence (Italy)

    2007-09-15

    To examine CMRglc measures and corresponding glucose transport (K{sub 1} and k{sub 2}) and phosphorylation (k{sub 3}) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 {+-} 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 {+-} 9 years, three females, median MMSE 30). Absolute CMRglc ({mu}mol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k{sub 3} reductions were found in the hippocampus, PCC and amygdala. K{sub 1} reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability. (orig.)

  4. Estimation of liver glucose metabolism after refeeding

    International Nuclear Information System (INIS)

    Rognstad, R.

    1987-01-01

    Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a 14 C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the 14 C yield from H 14 CO 3 - in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding

  5. Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

    Science.gov (United States)

    Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

    2008-02-01

    To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I = battery. We compared the FDG PET findings of each group of patients with controls. Group I patients frequently had memory and frontal executive dysfunction. They showed hypometabolism in the frontal cortex, anterior cerebellar hemisphere and vermis. They had parkinsonian motor deficits, but no basal ganglia hypometabolism. Group II and III patients frequently had multiple domain cognitive impairments, and showed hypometabolism in the frontal and parieto-temporal cortices. Hypometabolism of the bilateral caudate and the left posterolateral putamen was observed in Group II, and whole striatum in Group III. In summary, the cortical hypometabolism begins in the frontal cortex and spreads to the parieto-temporal cortex in MSA. This spreading pattern coincides with the progressive cognitive decline. Early caudate hypometabolism may also contribute to the cognitive impairment. Parkinsonian motor deficits precede putaminal hypometabolism that begins in its posterolateral part. Cerebellar hypometabolism occurs early in the clinical courses and seems to be a relevant metabolic descriptor of cerebellar deficits.

  6. Glucose metabolism of lactobacillus divergens

    International Nuclear Information System (INIS)

    De Bruyn, I.N.

    1987-02-01

    The aim of this study was to compile an optimal growth and selective medium for Lactobacillus divergens and to determine the pathway by which it metabolised glucose. The optimum growth temperature is 25 o C which is lower than that of most other lactobacilli. Citrate stimulates growth up to a concentration of 1% while acetate inhibits the organism at neutral pH, but it stimulates growth at pH 8.5 up to a concentration of 0.8%. MRS medium was therefore modified in order to obtain maximum growth of the organism. The acetate was omitted, sucrose was substituted for glucose and the pH was adjusted to 8.5. Sucrose was used, since a neutral pH is obtained after sterilisation of glucose in alkaline (pH ≥ 7.5) solution due to the degradation of glucose by the Maillard reaction. Various inhibitors and dyes were tested in order to formulate a selective medium. In the present study differently labelled glucose precursors were fermented by L. divergens and the fermentation products isolated by HPLC. The concentrations of acetate and formate were determined by comparison to a standard while the concentration of lactate and glucose was determined by enzymic assay. The radioactivity was determined by liquid scintillation counting and the positional labelling in lactate and acetate by chemical degradation. Fermentation of D-[U- 14 C]-glucose was included to correct for endogenous product dilution

  7. Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

    International Nuclear Information System (INIS)

    Casteels, Cindy; Martinez, Emili; Camon, Lluisa; Vera, Nuria de; Planas, Anna M.; Bormans, Guy; Baekelandt, Veerle; Laere, Koen van

    2010-01-01

    Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [ 18 F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB 1 ) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D 2 receptor availability and amphetamine-induced turning behaviour. Twenty-one Wistar rats (11 QA and 10 shams) were investigated. Small animal PET acquisitions were conducted on a Focus 220 with approximately 18 MBq of [ 18 F]MK-9470, [ 18 F]FDG and [ 11 C]raclopride. Relative glucose metabolism and parametric CB 1 receptor and D 2 binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2). In the QA model, [ 18 F]MK-9470 uptake, glucose metabolism and D 2 receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p -5 ), while an increase for these markers was observed on the contralateral side (>5%, all p -4 ). [ 18 F]MK-9470 binding was also increased in the cerebellum (p = 2.10 -5 ), where it was inversely correlated to the number of ipsiversive turnings (p = 7.10 -6 ), suggesting that CB 1 receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p = 1.10 -6 ). These data point to in vivo changes in endocannabinoid transmission, specifically for CB 1 receptors in the QA model, with involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D 2 and CB 1 neurotransmission in the contralateral hemisphere. (orig.)

  8. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

    Science.gov (United States)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W; Pfluger, Paul T; Fernandez, Ana M; Luquet, Serge; Woods, Stephen C; Torres-Alemán, Ignacio; Kahn, C Ronald; Götz, Magdalena; Horvath, Tamas L; Tschöp, Matthias H

    2016-08-11

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose

    International Nuclear Information System (INIS)

    Ackermann, R.F.; Lear, J.L.

    1989-01-01

    We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered [ 18 F]fluorodeoxyglucose (FDG) and [ 14 C]-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the 14 C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the 14 C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum

  10. Influence of ketamine on regional brain glucose use

    International Nuclear Information System (INIS)

    Davis, D.W.; Mans, A.M.; Biebuyck, J.F.; Hawkins, R.A.

    1988-01-01

    The purpose of this study was to determine the effect of different doses of ketamine on cerebral function at the level of individual brain structures as reflected by glucose use. Rats received either 5 or 30 mg/kg ketamine intravenously as a loading dose, followed by an infusion to maintain a steady-state level of the drug. An additional group received 30 mg/kg as a single injection only, and was studied 20 min later, by which time they were recovering consciousness (withdrawal group). Regional brain energy metabolism was evaluated with [6- 14 C]glucose and quantitative autoradiography during a 5-min experimental period. A subhypnotic, steady-state dose (5 mg/kg) of ketamine caused a stimulation of glucose use in most brain areas, with an average increase of 20%. At the larger steady-state dose (30 mg/kg, which is sufficient to cause anesthesia), there was no significant effect on most brain regions; some sensory nuclei were depressed (inferior colliculus, -29%; cerebellar dentate nucleus, -18%; vestibular nucleus, -16%), but glucose use in the ventral posterior hippocampus was increased by 33%. In contrast, during withdrawal from a 30-mg/kg bolus, there was a stimulation of glucose use throughout the brain (21-78%), at a time when plasma ketamine levels were similar to the levels in the 5 mg/kg group. At each steady-state dose, as well as during withdrawal, ketamine caused a notable stimulation of glucose use by the hippocampus

  11. Pattern of cerebral glucose metabolism on F-18 FDG brain PET during vomiting and symptom free periods in cyclic vomiting syndrome

    International Nuclear Information System (INIS)

    Kim, Yu Kyeong; Lee, Dong Soo; Kang, Eun Joo; Seo, Jeong Kee; Yeo, Jeong Seok; Chung, June Key; Lee, Myung Chul

    2001-01-01

    Cyclic Vomiting Syndrome (CVS) is characterized by recurrent, periodic, self-limiting vomiting. However, its pathogenesis is not yet established. We investigated the changes of the cerebral glucose metabolism using F-18 FDG during the vomiting attack and symptom free period in two children with CVS. FDG PET study showed the markedly increased metabolism in both temporal lobes and also in the medulla and cerebellum during the vomiting period. Also, FDG PET showed the decreased metabolism in the parieto-occipital and occipital areas during the in vomiting period. The area with decreased metabolism seemed to be related with the region showing abnormalities in EEG and perfusion SPECT studies. We expect that what we observed would be a helpful finding in clarifying the pathogenesis of the CVS

  12. Gut-Brain Glucose Signaling in Energy Homeostasis.

    Science.gov (United States)

    Soty, Maud; Gautier-Stein, Amandine; Rajas, Fabienne; Mithieux, Gilles

    2017-06-06

    Intestinal gluconeogenesis is a recently identified function influencing energy homeostasis. Intestinal gluconeogenesis induced by specific nutrients releases glucose, which is sensed by the nervous system surrounding the portal vein. This initiates a signal positively influencing parameters involved in glucose control and energy management controlled by the brain. This knowledge has extended our vision of the gut-brain axis, classically ascribed to gastrointestinal hormones. Our work raises several questions relating to the conditions under which intestinal gluconeogenesis proceeds and may provide its metabolic benefits. It also leads to questions on the advantage conferred by its conservation through a process of natural selection. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Impact of Hypoglycemia on Brain Metabolism During Diabetes.

    Science.gov (United States)

    Rehni, Ashish K; Dave, Kunjan R

    2018-04-10

    Diabetes is a metabolic disease afflicting millions of people worldwide. A substantial fraction of world's total healthcare expenditure is spent on treating diabetes. Hypoglycemia is a serious consequence of anti-diabetic drug therapy, because it induces metabolic alterations in the brain. Metabolic alterations are one of the central mechanisms mediating hypoglycemia-related functional changes in the brain. Acute, chronic, and/or recurrent hypoglycemia modulate multiple metabolic pathways, and exposure to hypoglycemia increases consumption of alternate respiratory substrates such as ketone bodies, glycogen, and monocarboxylates in the brain. The aim of this review is to discuss hypoglycemia-induced metabolic alterations in the brain in glucose counterregulation, uptake, utilization and metabolism, cellular respiration, amino acid and lipid metabolism, and the significance of other sources of energy. The present review summarizes information on hypoglycemia-induced metabolic changes in the brain of diabetic and non-diabetic subjects and the manner in which they may affect brain function.

  14. Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

    DEFF Research Database (Denmark)

    Gejl, Michael; Lerche, Susanne; Egefjord, Lærke

    2013-01-01

    phosphorylation velocity (V max) in the gray matter regions of cerebral cortex, thalamus, and cerebellum, as well as increased blood-brain glucose transport capacity (T max) in gray matter, white matter, cortex, thalamus, and cerebellum. In hypoglycemia, GLP-1 had no effects on net glucose metabolism, brain...

  15. Sleep Control, GPCRs, and Glucose Metabolism.

    Science.gov (United States)

    Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

    2016-09-01

    Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. Copyright © 2016. Published by Elsevier Ltd.

  16. Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6- 13C 2]glucose and [1,2- 13C 2]acetate

    Science.gov (United States)

    Deelchand, Dinesh K.; Nelson, Christopher; Shestov, Alexander A.; Uğurbil, Kâmil; Henry, Pierre-Gilles

    2009-02-01

    In this work the feasibility of measuring neuronal-glial metabolism in rat brain in vivo using co-infusion of [1,6- 13C 2]glucose and [1,2- 13C 2]acetate was investigated. Time courses of 13C spectra were measured in vivo while infusing both 13C-labeled substrates simultaneously. Individual 13C isotopomers (singlets and multiplets observed in 13C spectra) were quantified automatically using LCModel. The distinct 13C spectral pattern observed in glutamate and glutamine directly reflected the fact that glucose was metabolized primarily in the neuronal compartment and acetate in the glial compartment. Time courses of concentration of singly and multiply-labeled isotopomers of glutamate and glutamine were obtained with a temporal resolution of 11 min. Although dynamic metabolic modeling of these 13C isotopomer data will require further work and is not reported here, we expect that these new data will allow more precise determination of metabolic rates as is currently possible when using either glucose or acetate as the sole 13C-labeled substrate.

  17. Mechanisms and significance of brain glucose signaling in energy balance, glucose homeostasis, and food-induced reward.

    Science.gov (United States)

    Devarakonda, Kavya; Mobbs, Charles V

    2016-12-15

    The concept that hypothalamic glucose signaling plays an important role in regulating energy balance, e.g., as instantiated in the so-called "glucostat" hypothesis, is one of the oldest in the field of metabolism. However the mechanisms by which neurons in the hypothalamus sense glucose, and the function of glucose signaling in the brain, has been difficult to establish. Nevertheless recent studies probing mechanisms of glucose signaling have also strongly supported a role for glucose signaling in regulating energy balance, glucose homeostasis, and food-induced reward. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain.

    Science.gov (United States)

    Wakabayashi, Ken T; Spekterman, Laurence; Kiyatkin, Eugene A

    2016-06-01

    Glucose, a primary metabolic substrate for cellular activity, must be delivered to the brain for normal neural functions. Glucose is also a unique reinforcer; in addition to its rewarding sensory properties and metabolic effects, which all natural sugars have, glucose crosses the blood-brain barrier and acts on glucoreceptors expressed on multiple brain cells. To clarify the role of this direct glucose action in the brain, we compared the neural and behavioural effects of glucose with those induced by fructose, a sweeter yet metabolically equivalent sugar. First, by using enzyme-based biosensors in freely moving rats, we confirmed that glucose rapidly increased in the nucleus accumbens in a dose-dependent manner after its intravenous delivery. In contrast, fructose induced a minimal response only after a large-dose injection. Second, we showed that naive rats during unrestricted access consumed larger volumes of glucose than fructose solution; the difference appeared with a definite latency during the initial exposure and strongly increased during subsequent tests. When rats with equal sugar experience were presented with either glucose or fructose in alternating order, the consumption of both substances was initially equal, but only the consumption of glucose increased during subsequent sessions. Finally, rats with equal glucose-fructose experience developed a strong preference for glucose over fructose during a two-bottle choice procedure; the effect appeared with a definite latency during the initial test and greatly amplified during subsequent tests. Our results suggest that direct entry of glucose in the brain and its subsequent effects on brain cells could be critical for the experience-dependent escalation of glucose consumption and the development of glucose preference over fructose. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  19. Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

    OpenAIRE

    Yao, Junjie; Xia, Jun; Maslov, Konstantin I.; Nasiriavanaki, Mohammadreza; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

    2012-01-01

    We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood–brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for ...

  20. Hypothalamic control of energy and glucose metabolism.

    Science.gov (United States)

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  1. Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?

    Directory of Open Access Journals (Sweden)

    José Pedro Castro

    2018-04-01

    Full Text Available The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis, cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function has been observed during aging, metabolic diseases such as type 2 diabetes and in neurodegenerative diseases such as Alzheimer’s (AD, Parkinson’s (PD or even Huntington’s (HD diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.

  2. Regional cerebral glucose metabolism during sevoflurane anaesthesia in healthy subjects studied with positron emission tomography

    DEFF Research Database (Denmark)

    Schlünzen, L; Juul, N; Hansen, K V

    2010-01-01

    BACKGROUND: The precise mechanism by which sevoflurane exerts its effects in the human brain remains unknown. In the present study, we quantified the effects of sevoflurane on regional cerebral glucose metabolism (rGMR) in the human brain measured with positron emission tomography. METHODS: Eight...... areas by 48-71% of the baseline (Pbrain metabolic reduction of GMR in all regions...... of the human brain, with the most marked metabolic suppression in the lingual gyrus, thalamus and occipital lobe....

  3. Serotonin metabolism in rat brain

    International Nuclear Information System (INIS)

    Schutte, H.H.

    1976-01-01

    The metabolism of serotonin in rat brain was studied by measuring specific activities of tryptophan in plasma and of serotonin, 5-hydroxyindole acetic acid and tryptophan in the brain after intravenous injection of tritiated tryptophan. For a detailed analysis of the specific activities, a computer simulation technique was used. It was found that only a minor part of serotonin in rat brain is synthesized from tryptophan rapidly transported from the blood. It is suggested that the brain tryptophan originates from brain proteins. It was also found that the serotonin in rat brain is divided into more than one metabolic compartment

  4. Insulin action in brain regulates systemic metabolism and brain function.

    Science.gov (United States)

    Kleinridders, André; Ferris, Heather A; Cai, Weikang; Kahn, C Ronald

    2014-07-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. © 2014 by the American Diabetes Association.

  5. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    International Nuclear Information System (INIS)

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M.

    2007-01-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography

  6. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M. [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography.

  7. Comparison of Glutamate Turnover in Nerve Terminals and Brain Tissue During [1,6-13C2]Glucose Metabolism in Anesthetized Rats.

    Science.gov (United States)

    Patel, Anant B; Lai, James C K; Chowdhury, Golam I M; Rothman, Douglas L; Behar, Kevin L

    2017-01-01

    The 13 C turnover of neurotransmitter amino acids (glutamate, GABA and aspartate) were determined from extracts of forebrain nerve terminals and brain homogenate, and fronto-parietal cortex from anesthetized rats undergoing timed infusions of [1,6- 13 C 2 ]glucose or [2- 13 C]acetate. Nerve terminal 13 C fractional labeling of glutamate and aspartate was lower than those in whole cortical tissue at all times measured (up to 120 min), suggesting either the presence of a constant dilution flux from an unlabeled substrate or an unlabeled (effectively non-communicating on the measurement timescale) glutamate pool in the nerve terminals. Half times of 13 C labeling from [1,6- 13 C 2 ]glucose, as estimated by least squares exponential fitting to the time course data, were longer for nerve terminals (Glu C4 , 21.8 min; GABA C2 21.0 min) compared to cortical tissue (Glu C4 , 12.4 min; GABA C2 , 14.5 min), except for Asp C3 , which was similar (26.5 vs. 27.0 min). The slower turnover of glutamate in the nerve terminals (but not GABA) compared to the cortex may reflect selective effects of anesthesia on activity-dependent glucose use, which might be more pronounced in the terminals. The 13 C labeling ratio for glutamate-C4 from [2- 13 C]acetate over that of 13 C-glucose was twice as large in nerve terminals compared to cortex, suggesting that astroglial glutamine under the 13 C glucose infusion was the likely source of much of the nerve terminal dilution. The net replenishment of most of the nerve terminal amino acid pools occurs directly via trafficking of astroglial glutamine.

  8. Brain Lactate Metabolism in Humans With Subarachnoid Hemorrhage

    OpenAIRE

    Oddo M; Levine JM; Frangos S; Maloney-Wilensky E; Carrera E; Daniel RT; Levivier M; Magistretti PJ; LeRoux PD

    2012-01-01

    Abstract BACKGROUND AND PURPOSE: Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. METHODS: Thirty one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxi...

  9. The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo

    DEFF Research Database (Denmark)

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    2012-01-01

    The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow...... not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation......, and especially temporal relationships must be taken into account. What triggers the flow increase during functional brain activation is not entirely elucidated. The demand for excess glucose uptake may be important and a possible oxygen deficit in tissue distant from the capillaries is probably of minor...

  10. Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

    Science.gov (United States)

    Yao, Junjie; Xia, Jun; Maslov, Konstantin; Avanaki, Mohammadreza R. N.; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

    2013-03-01

    To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

  11. A combined microdialysis and FDG-PET study of glucose metabolism in head injury.

    Science.gov (United States)

    Hutchinson, Peter J; O'Connell, Mark T; Seal, Alex; Nortje, Jurgens; Timofeev, Ivan; Al-Rawi, Pippa G; Coles, Jonathan P; Fryer, Timothy D; Menon, David K; Pickard, John D; Carpenter, Keri L H

    2009-01-01

    Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Positron emission tomography (PET) establishes metabolism of the whole brain but only for the scan's duration. This study's objective was to apply these techniques together, in patients with traumatic brain injury, to assess the relationship between microdialysis (extracellular glucose, lactate, pyruvate, and the lactate/pyruvate (L/P) ratio as a marker of anaerobic metabolism) and PET parameters of glucose metabolism using the glucose analogue [(18)F]-fluorodeoxyglucose (FDG). In particular, we aimed to determine the fate of glucose in terms of differential metabolism to pyruvate and lactate. Microdialysis catheters (CMA70 or CMA71) were inserted into the cerebral cortex of 17 patients with major head injury. Microdialysis was performed during FDG-PET scans with regions of interest for PET analysis defined by the location of the gold-tipped microdialysis catheter. Microdialysate analysis was performed on a CMA600 analyser. There was significant linear relationship between the PET-derived parameter of glucose metabolism (regional cerebral metabolic rate of glucose; CMRglc) and levels of lactate (r = 0.778, p glucose was metabolised to both lactate and pyruvate, but was not associated with an increase in the L/P ratio. This suggests an increase in glucose metabolism to both lactate and pyruvate, as opposed to a shift towards anaerobic metabolism.

  12. Effects of diabetes on brain metabolism - is brain glycogen a significant player?

    DEFF Research Database (Denmark)

    Sickmann, Helle M; Waagepetersen, Helle S.

    2015-01-01

    Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the br......Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose...... to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may...... understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes....

  13. Study of brain metabolism using positron emission computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Heiss, W D

    1983-03-21

    Positron emission tomography permits the three-dimensional regional measurement of metabolism and blood flow in the brain. For the determination of cerebral metabolic rates of glucose by PET /sup 18/fluordeoxyglucose is usually applied: cerebral metabolic rate of glucose was found to be 36 to 47 ..mu..mol/100 g/min in the grey matter and 23 to 29 ..mu..mol/100 g/min in the white matter of normal volunteers. During physiologic activation metabolic rate of glucose is increased in the respective brain areas in relation to the strength and complexity of the stimulation. In patients suffering from ischaemic stroke glucose metabolism is markedly decreased within the infarction. Additonally, glucose metabolism is reduced by 20% in morphologically intact areas of the homolateral cortex, in the basal ganglia, in the cortical area contralateral to the infarction and in the contralateral cerebellum. This remote reduction of glucose utilization is probably caused by functional inactivation of these brain structures; it could be responsible for the diffuse organic syndrome in stroke victims not caused by the focal lesion. In patients suffering from dementia of the multi-infarct type and of the Alzheimer type glucose metabolism is reduced; the lesions in Alzheimer cases are most prominent in partietal and frontal cortical areas. In Chorea Huntington cases glucose metabolism is primarily disturbed in the striate, especially in the caudate nucleus; in these cases the metabolic disturbance can be detected earlier than the atrophy in computed tomograms. Disturbances of glucose and oxygen utilization are not necessary causes, but may also be sequelae od functional impairment. Additional information on pathogentic mechanisms may be obtained by the investigation of the protein synthesis.

  14. Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

    Science.gov (United States)

    Patet, Camille; Quintard, Hervé; Suys, Tamarah; Bloch, Jocelyne; Daniel, Roy T; Pellerin, Luc; Magistretti, Pierre J; Oddo, Mauro

    2015-10-15

    Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r = 0.56; p 25. The correlation between blood and brain glucose also decreased from r = 0.62 to r = 0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

  15. Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

    Science.gov (United States)

    Yao, Junjie; Xia, Jun; Maslov, Konstantin I.; Nasiriavanaki, Mohammadreza; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

    2012-01-01

    We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively decoupled by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area had a clear vascular pattern and spread wider than the somatosensory region. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism. PMID:22940116

  16. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

    Science.gov (United States)

    Gjedde, Albert; Crone, Christian

    1981-10-01

    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

  17. Metabolic Profiles of Brain Metastases

    Directory of Open Access Journals (Sweden)

    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  18. Insights into Brain Glycogen Metabolism

    Science.gov (United States)

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  19. CREBH Regulates Systemic Glucose and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Yoshimi Nakagawa

    2018-05-01

    Full Text Available The cyclic adenosine monophosphate (cAMP-responsive element-binding protein H (CREBH, encoded by CREB3L3 is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine.

  20. Cerebral glucose metabolism in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

    1984-02-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

  1. Cerebral glucose metabolism in Parkinson's disease

    International Nuclear Information System (INIS)

    Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

    1984-01-01

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

  2. Pre-symptomatic activation of antioxidant responses and alterations in glucose and pyruvate metabolism in Niemann-Pick Type C1-deficient murine brain.

    Directory of Open Access Journals (Sweden)

    Barry E Kennedy

    Full Text Available Niemann-Pick Type C (NPC disease is an autosomal recessive neurodegenerative disorder caused in most cases by mutations in the NPC1 gene. NPC1-deficiency is characterized by late endosomal accumulation of cholesterol, impaired cholesterol homeostasis, and a broad range of other cellular abnormalities. Although neuronal abnormalities and glial activation are observed in nearly all areas of the brain, the most severe consequence of NPC1-deficiency is a near complete loss of Purkinje neurons in the cerebellum. The link between cholesterol trafficking and NPC pathogenesis is not yet clear; however, increased oxidative stress in symptomatic NPC disease, increases in mitochondrial cholesterol, and alterations in autophagy/mitophagy suggest that mitochondria play a role in NPC disease pathology. Alterations in mitochondrial function affect energy and neurotransmitter metabolism, and are particularly harmful to the central nervous system. To investigate early metabolic alterations that could affect NPC disease progression, we performed metabolomics analyses of different brain regions from age-matched wildtype and Npc1 (-/- mice at pre-symptomatic, early symptomatic and late stage disease by (1H-NMR spectroscopy. Metabolic profiling revealed markedly increased lactate and decreased acetate/acetyl-CoA levels in Npc1 (-/- cerebellum and cerebral cortex at all ages. Protein and gene expression analyses indicated a pre-symptomatic deficiency in the oxidative decarboxylation of pyruvate to acetyl-CoA, and an upregulation of glycolytic gene expression at the early symptomatic stage. We also observed a pre-symptomatic increase in several indicators of oxidative stress and antioxidant response systems in Npc1 (-/- cerebellum. Our findings suggest that energy metabolism and oxidative stress may present additional therapeutic targets in NPC disease, especially if intervention can be started at an early stage of the disease.

  3. Brain glucose and lactate levels during ventilator-induced hypo- and hypercapnia

    NARCIS (Netherlands)

    van Hulst, R. A.; Lameris, T. W.; Haitsma, J. J.; Klein, J.; Lachmann, B.

    2004-01-01

    OBJECTIVE: Levels of glucose and lactate were measured in the brain by means of microdialysis in order to evaluate the effects of ventilator-induced hypocapnia and hypercapnia on brain metabolism in healthy non-brain-traumatized animals. DESIGN AND SETTING: Prospective animal study in a university

  4. Simultaneous measurement of glucose transport and utilization in the human brain

    Science.gov (United States)

    Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.

    2011-01-01

    Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMRglc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMRglc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain. PMID:21791622

  5. Abnormal brain glucose metabolism and depressive mood in patients with pre-dialytic chronic kidney disease: SPM analysis of F-18 FDG positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Sung Min; Song, Sang Heon; Kim, Seong Jang; Kim, Ji Hoon; Kwak, Ihm Soo; Kim, In Ju; Kim, Yong Ki [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    The aim of this study was to investigate the relationship between depressive mood and pre-dialytic CKD, to localize and quantify depressive mood -related lesions in pre-dialytic CKD patients through statistical parametric mapping (SPM) analysis of brain positron emission tomography (PET), and to examine the usefulness of brain PET for early detection and proper treatment of depressive mood. Twenty one patients with stage 5 CKD and 22 healthy volunteers were analyzed by depressive mood assessment and statistical parametric mapping (SPM) analysis of 18F-FDG PET. Depressive mood assessment was done by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). The largest clusters were areas including precentral gyrus, prefrontal cortex, and anterior cingulated cortex of left hemisphere. Other clusters were left transverse temporal gyrus, left superior temporal gyrus, right prefrontal cortex, right dorsolateral prefrontal cortex (BA 46, 44), right inferior frontal gyrus, right inferior parietal lobule, left angular gyrus. In addition, correlation was found between hypometabolized areas and HDRS scores of CKD patients in right prefrontal cortex (BA 11) and right anterior cingulated gyrus (BA 24). In conclusion, this study demonstrated specific depressive mood-related abnormal metabolic lesion. Interestingly, in CKD patients with severe depressive mood, cerebral metabolism was similar to that of MDD.

  6. Abnormal brain glucose metabolism and depressive mood in patients with pre-dialytic chronic kidney disease: SPM analysis of F-18 FDG positron emission tomography

    International Nuclear Information System (INIS)

    Jun, Sung Min; Song, Sang Heon; Kim, Seong Jang; Kim, Ji Hoon; Kwak, Ihm Soo; Kim, In Ju; Kim, Yong Ki

    2007-01-01

    The aim of this study was to investigate the relationship between depressive mood and pre-dialytic CKD, to localize and quantify depressive mood -related lesions in pre-dialytic CKD patients through statistical parametric mapping (SPM) analysis of brain positron emission tomography (PET), and to examine the usefulness of brain PET for early detection and proper treatment of depressive mood. Twenty one patients with stage 5 CKD and 22 healthy volunteers were analyzed by depressive mood assessment and statistical parametric mapping (SPM) analysis of 18F-FDG PET. Depressive mood assessment was done by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). The largest clusters were areas including precentral gyrus, prefrontal cortex, and anterior cingulated cortex of left hemisphere. Other clusters were left transverse temporal gyrus, left superior temporal gyrus, right prefrontal cortex, right dorsolateral prefrontal cortex (BA 46, 44), right inferior frontal gyrus, right inferior parietal lobule, left angular gyrus. In addition, correlation was found between hypometabolized areas and HDRS scores of CKD patients in right prefrontal cortex (BA 11) and right anterior cingulated gyrus (BA 24). In conclusion, this study demonstrated specific depressive mood-related abnormal metabolic lesion. Interestingly, in CKD patients with severe depressive mood, cerebral metabolism was similar to that of MDD

  7. Effect of different glucose supply conditions on neuronal energy metabolism

    OpenAIRE

    Zheng, Hongwen; Wang, Rubin; Qu, Jingyi

    2016-01-01

    The glucose-excited neurons in brain can sense blood glucose levels and reflect different firing states, which are mainly associated with regulation of blood glucose and energy demand in the brain. In this paper, a new model of glucose-excited neuron in hypothalamus is proposed. The firing properties and energy consumption of this type of neuron under conditions of different glucose levels are simulated and analyzed. The results show that the firing rate and firing duration of the neuron both...

  8. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism.

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John D R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-04-23

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.

  9. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

  10. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    OpenAIRE

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2015-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

  11. Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized C-13 magnetic resonance

    DEFF Research Database (Denmark)

    Mishkovsky, Mor; Anderson, Brian; Karlsson, Magnus

    2017-01-01

    The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, C-13 magnetic resonance spectroscopy (MRS) allows following the fate of C-13-enriched substrates through metabolic pathways. We herein...... glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner....... demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized C-13 MRS. In particular, the dynamic C-13-labeling of pyruvate and lactate formed from C-13-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-H-2(5), 3...

  12. Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate.

    Science.gov (United States)

    Valdebenito, Rocío; Ruminot, Iván; Garrido-Gerter, Pamela; Fernández-Moncada, Ignacio; Forero-Quintero, Linda; Alegría, Karin; Becker, Holger M; Deitmer, Joachim W; Barros, L Felipe

    2016-10-01

    The effectiveness of ketogenic diets and intermittent fasting against neurological disorders has brought interest to the effects of ketone bodies on brain cells. These compounds are known to modify the metabolism of neurons, but little is known about their effect on astrocytes, cells that control the supply of glucose to neurons and also modulate neuronal excitability through the glycolytic production of lactate. Here we have used genetically-encoded Förster Resonance Energy Transfer nanosensors for glucose, pyruvate and ATP to characterize astrocytic energy metabolism at cellular resolution. Our results show that the ketone body beta-hydroxybutyrate strongly inhibited astrocytic glucose consumption in mouse astrocytes in mixed cultures, in organotypic hippocampal slices and in acute hippocampal slices prepared from ketotic mice, while blunting the stimulation of glycolysis by physiological and pathophysiological stimuli. The inhibition of glycolysis was paralleled by an increased ability of astrocytic mitochondria to metabolize pyruvate. These results support the emerging notion that astrocytes contribute to the neuroprotective effect of ketone bodies. © The Author(s) 2015.

  13. Age differences in intercorrelations between regional cerebral metabolic rates for glucose

    International Nuclear Information System (INIS)

    Horwitz, B.; Duara, R.; Rapoport, S.I.

    1986-01-01

    Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole-brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using [18F]fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men

  14. A brain-liver circuit regulates glucose homeostasis.

    Science.gov (United States)

    Pocai, Alessandro; Obici, Silvana; Schwartz, Gary J; Rossetti, Luciano

    2005-01-01

    Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.

  15. Introduction to the Thematic Minireview Series: Brain glycogen metabolism.

    Science.gov (United States)

    Carlson, Gerald M; Dienel, Gerald A; Colbran, Roger J

    2018-05-11

    The synthesis of glycogen allows for efficient intracellular storage of glucose molecules in a soluble form that can be rapidly released to enter glycolysis in response to energy demand. Intensive studies of glucose and glycogen metabolism, predominantly in skeletal muscle and liver, have produced innumerable insights into the mechanisms of hormone action, resulting in the award of several Nobel Prizes over the last one hundred years. Glycogen is actually present in all cells and tissues, albeit at much lower levels than found in muscle or liver. However, metabolic and physiological roles of glycogen in other tissues are poorly understood. This series of Minireviews summarizes what is known about the enzymes involved in brain glycogen metabolism and studies that have linked glycogen metabolism to multiple brain functions involving metabolic communication between astrocytes and neurons. Recent studies unexpectedly linking some forms of epilepsy to mutations in two poorly understood proteins involved in glycogen metabolism are also reviewed. © 2018 Carlson et al.

  16. Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls

    Directory of Open Access Journals (Sweden)

    Rong Zhang

    2016-01-01

    Full Text Available Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB, diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA model of 755 identified or putatively identified metabolites. Orthogonal partial least square discriminant analysis (OPLSDA produced clear separation between 17 of the controls and 19 of the SDB samples (R2CUM 0.976, Q2 0.671, p-value of the cross-validated ANOVA score 0.0024. The most important metabolites producing discrimination were the lipophilic amino acids leucine/isoleucine, proline, methionine, phenylalanine, and tyrosine; the neurotransmitters GABA and NAAG and sugar metabolites sorbitol, gluconic acid, xylitol, ribitol, arabinotol, and erythritol. Eight samples from diabetic brains were analysed, six of which grouped with the SDB samples without compromising the model (R2 CUM 0.850, Q2 CUM 0.534, p-value for cross-validated ANOVA score 0.00087. There appears on the basis of this small sample set to be some commonality between metabolic perturbations resulting from diabetes and from SDB.

  17. A review of metabolism of labeled glucoses for use in measuring glucose recycling

    International Nuclear Information System (INIS)

    Russell, R.W.; Young, J.W.

    1990-01-01

    The fate of tritium from each carbon of D-glucose and the metabolism of L-glucose and 2-deoxy-D-glucose are known. Differences in metabolism of labeled glucoses can be used to quantify physical and chemical recycling of glucose. Only physical recycling is measured by [1- 3 H]-L-glucose, whereas [U- 14 C]-D-glucose measures total recycling. The difference between [1- 3 H]-L-glucose and [U- 14 C]-D-glucose, therefore, is chemical recycling. Recycling from extracellular binding sites and hepatic glucose 6-phosphate can be measured by difference between [1,2- 3 H]-2-deoxy-D-glucose and [1- 3 H]-L-glucose, and the difference in irreversible loss of the two will measure extrahepatic uptake of D-glucose. Recycling via Cori-alanine cycle plus CO 2 is the difference in irreversible loss measured by using [6- 3 H]-glucose and [U- 14 C]-D-glucose. Recycling via the hexose monophosphate pathway can be determined by difference in irreversible loss between [1- 3 H]-D-glucose and [6- 3 H]-D-glucose. Recycling via CO 2 and glycerol must be measured directly with [U- 14 C]glucose, bicarbonate, and glycerol. Recycling via hepatic glycogen can be estimated by subtracting all other measured chemical recycling from total chemical recycling. This review describes means to quantify glucose recycling in vivo, enabling studies of mechanisms for conservation and utilization of glucose. 54 references

  18. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    International Nuclear Information System (INIS)

    Schroeck, H.K.; Kuschinsky, W.

    1989-01-01

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-[14C]antipyrine and 2-[14C]deoxy-D-glucose method. The treatment induced moderate [15 days, base excess (BE) 16 mM] to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis

  19. Asymmetry of cerebral glucose metabolism in very low-birth-weight infants without structural abnormalities.

    Directory of Open Access Journals (Sweden)

    Jae Hyun Park

    Full Text Available Thirty-six VLBW infants who underwent F-18 fluorodeoxyglucose (F-18 FDG brain PET and MRI were prospectively enrolled, while infants with evidence of parenchymal brain injury on MRI were excluded. The regional glucose metabolic ratio and asymmetry index were calculated. The asymmetry index more than 10% (right > left asymmetry or less than -10% (left > right asymmetry were defined as abnormal. Regional cerebral glucose metabolism were compared between right and left cerebral hemispheres, and between the following subgroups: multiple gestations, premature rupture of membrane, bronchopulmonary dysplasia, and low-grade intraventricular hemorrhage.In the individual analysis, 21 (58.3% of 36 VLBW infants exhibited asymmetric cerebral glucose metabolism. Fifteen infants (41.7% exhibited right > left asymmetry, while six (16.7% exhibited left > right asymmetry. In the regional analysis, right > left asymmetry was more extensive than left > right asymmetry. The metabolic ratio in the right frontal, temporal, and occipital cortices and right thalamus were significantly higher than those in the corresponding left regions. In the subgroup analyses, the cerebral glucose metabolism in infants with multiple gestations, premature rupture of membrane, bronchopulmonary dysplasia, or low-grade intraventricular hemorrhage were significantly lower than those in infants without these.VLBW infants without structural abnormalities have asymmetry of cerebral glucose metabolism. Decreased cerebral glucose metabolism are noted in infants with neurodevelopmental risk factors. F-18 FDG PET could show microstructural abnormalities not detected by MRI in VLBW infants.

  20. Acute effect of glucose on cerebral blood flow, blood oxygenation, and oxidative metabolism.

    Science.gov (United States)

    Xu, Feng; Liu, Peiying; Pascual, Juan M; Xiao, Guanghua; Huang, Hao; Lu, Hanzhang

    2015-02-01

    While it is known that specific nuclei of the brain, for example hypothalamus, contain glucose-sensing neurons thus their activity is affected by blood glucose level, the effect of glucose modulation on whole-brain metabolism is not completely understood. Several recent reports have elucidated the long-term impact of caloric restriction on the brain, showing that animals under caloric restriction had enhanced rate of tricarboxylic acid cycle (TCA) cycle flux accompanied by extended life span. However, acute effect of postprandial blood glucose increase has not been addressed in detail, partly due to a scarcity and complexity of measurement techniques. In this study, using a recently developed noninvasive MR technique, we measured dynamic changes in global cerebral metabolic rate of O2 (CMRO2 ) following a 50 g glucose ingestion (N = 10). A time dependent decrease in CMRO2 was observed, which was accompanied by a reduction in oxygen extraction fraction (OEF) with unaltered cerebral blood flow (CBF). At 40 min post-ingestion, the amount of CMRO2 reduction was 7.8 ± 1.6%. A control study without glucose ingestion was performed (N = 10), which revealed no changes in CMRO2 , CBF, or OEF, suggesting that the observations in the glucose study was not due to subject drowsiness or fatigue after staying inside the scanner. These findings suggest that ingestion of glucose may alter the rate of cerebral metabolism of oxygen in an acute setting. © 2014 Wiley Periodicals, Inc.

  1. Regional characterization of energy metabolism in the brain of normal and MPTP-intoxicated mice using new markers of glucose and phosphate transport

    Directory of Open Access Journals (Sweden)

    Touhami Jawida

    2010-12-01

    Full Text Available Abstract The gibbon ape leukemia virus (GALV, the amphotropic murine leukemia virus (AMLV and the human T-cell leukemia virus (HTLV are retroviruses that specifically bind nutrient transporters with their envelope glycoproteins (Env when entering host cells. Here, we used tagged ligands derived from GALV, AMLV, and HTLV Env to monitor the distribution of their cognate receptors, the inorganic phosphate transporters PiT1 and PiT2, and the glucose transporter GLUT1, respectively, in basal conditions and after acute energy deficiency. For this purpose, we monitored changes in the distribution of PiT1, PiT2 and GLUT1 in the cerebellum, the frontal cortex, the corpus callosum, the striatum and the substantia nigra (SN of C57/BL6 mice after administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridinium (MPTP, a mitochondrial complex I inhibitor which induces neuronal degeneration in the striato-nigral network. The PiT1 ligand stained oligodendrocytes in the corpus callosum and showed a reticular pattern in the SN. The PiT2 ligand stained particularly the cerebellar Purkinje cells, while GLUT1 labelling was mainly observed throughout the cortex, basal ganglia and cerebellar gray matter. Interestingly, unlike GLUT1 and PiT2 distributions which did not appear to be modified by MPTP intoxication, PiT1 immunostaining seemed to be more extended in the SN. The plausible reasons for this change following acute energy stress are discussed. These new ligands therefore constitute new metabolic markers which should help to unravel cellular adaptations to a wide variety of normal and pathologic conditions and to determine the role of specific nutrient transporters in tissue homeostasis.

  2. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  3. Local cerebral blood flow and glucose metabolism during seizure in spontaneously epileptic El mice

    International Nuclear Information System (INIS)

    Hosokawa, Chisa; Ochi, Hironobu; Yamagami, Sakae; Kawabe, Joji; Kobashi, Toshiko; Okamura, Terue; Yamada, Ryusaku

    1995-01-01

    Local cerebral blood flow and glucose metabolism were examined in spontaneously epileptic El mice using autoradiography with 125 I-IMP and 14 C-DG in the interictal phase and during seizure. El (+) mice that developed generalized tonic-clonic convulsions and El (-) mice that received no stimulation and had no history of epileptic seizures were examined. The seizure non-susceptible, maternal strain ddY mice were used as control. Uptake ratios for IMP and DG in mouse brain were calculated using the autoradiographic density. In the interictal phase, the pattern of local cerebral blood flow of El (+) mice was similar to that of ddY and El (-) mice, and glucose metabolism in the hippocampus was higher in El (+) mice than in El (-) and ddY mice, but flow and metabolism were nearly matched. During seizure, no significant changed blood flow and increased glucose metabolism in the hippocampus, the epileptic focus, and no markedly changed blood flow and depressed glucose metabolism in other brain regions were observed and considered to be flow-metabolism uncoupling. These observations have never been reported in clinical or experimental studies of epilepsy. Seizures did not cause large regional differences in cerebral blood flow. Therefore, only glucose metabolism is useful for detection of the focus of secondary generalized seizures in El mice, and appeared possibly to be related to the pathophysiology of secondary generalized epilepsy in El mice. (author)

  4. Acute effects of sodium valproate and gamma-vinyl GABA on regional amino acid metabolism in the rat brain: incorporation of 2-[14C]glucose into amino acids.

    Science.gov (United States)

    Chapman, A G; Riley, K; Evans, M C; Meldrum, B S

    1982-09-01

    Amino acid concentrations have been determined in rat brain regions (cortex, striatum, cerebellum, and hippocampus) by HPLC after administration of acute anticonvulsant doses of sodium valproate (400 mg/kg, i.p.) and gamma-vinyl-GABA (1 g/kg, i.p.). After valproate administration the GABA level increases only in the cortex; aspartic acid concentration decreases in the cortex and hippocampus, and glutamic acid decreases in the hippocampus and striatum and increases in the cortex and cerebellum. There are no changes in the concentrations of glutamine, taurine, glycine, serine, and alanine following valproate administration. Only the GABA level increases in all the regions after gamma-vinyl-GABA administration. Cortical analyses 2, 4 and 10 minutes after pulse labeling with 2-[14C]glucose, i.v., show no change in the rate of cortical glucose utilization in the valproate treated group. The rate of labeling of glutamic acid is also unchanged, but the rate of labeling of GABA is reduced following valproate administration. After gamma-vinyl-GABA administration there is no change in the rate of labeling of GABA. These biochemical findings can be interpreted in terms of a primary anticonvulsant action of valproate on membrane receptors with secondary effects on the metabolism of amino acid neurotransmitters. This contrasts with the primary action of gamma-vinyl-GABA on GABA-transaminase activity.

  5. GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish.

    Science.gov (United States)

    Marín-Juez, Rubén; Rovira, Mireia; Crespo, Diego; van der Vaart, Michiel; Spaink, Herman P; Planas, Josep V

    2015-01-01

    Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing.

  6. Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

    Science.gov (United States)

    Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

    2017-01-01

    Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

    Directory of Open Access Journals (Sweden)

    Anne Abot

    2018-04-01

    Full Text Available Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes

  8. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability

    NARCIS (Netherlands)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W.; Pfluger, Paul T.; Fernandez, Ana M.; Luquet, Serge; Woods, Stephen C.; Torres-Alemán, Ignacio; Kahn, C. Ronald; Götz, Magdalena; Horvath, Tamas L.; Tschöp, Matthias H.

    2016-01-01

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and

  9. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    KAUST Repository

    Magistretti, Pierre J.

    2015-05-01

    The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

  10. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  11. The effects of incretin hormones on cerebral glucose metabolism in health and disease

    DEFF Research Database (Denmark)

    Nilsson, Malin; Gjedde, Albert; Brock, Birgitte

    2017-01-01

    Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies......, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia. GLP-1, when administered as long-acting analogues...... or intravenously, appears to decrease transport of glucose in normoglycaemic conditions, without affecting the total cerebral glucose content. During hypoglycaemia this effect seems abated, whereas during hyperglycaemia GLP-1 regulates cerebral glucose metabolism towards stable levels resembling normoglycaemia...

  12. Astrocyte glycogen and brain energy metabolism.

    Science.gov (United States)

    Brown, Angus M; Ransom, Bruce R

    2007-09-01

    The brain contains glycogen but at low concentration compared with liver and muscle. In the adult brain, glycogen is found predominantly in astrocytes. Astrocyte glycogen content is modulated by a number of factors including some neurotransmitters and ambient glucose concentration. Compelling evidence indicates that astrocyte glycogen breaks down during hypoglycemia to lactate that is transferred to adjacent neurons or axons where it is used aerobically as fuel. In the case of CNS white matter, this source of energy can extend axon function for 20 min or longer. Likewise, during periods of intense neural activity when energy demand exceeds glucose supply, astrocyte glycogen is degraded to lactate, a portion of which is transferred to axons for fuel. Astrocyte glycogen, therefore, offers some protection against hypoglycemic neural injury and ensures that neurons and axons can maintain their function during very intense periods of activation. These emerging principles about the roles of astrocyte glycogen contradict the long held belief that this metabolic pool has little or no functional significance.

  13. Vitamins and glucose metabolism: The role of static magnetic fields.

    Science.gov (United States)

    Lahbib, Aïda; Ghodbane, Soumaya; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-12-01

    This review focuses on our own data and other data from the literature of static magnetic fields (SMF) bioeffects and vitamins and glucose metabolism. Three main areas of investigation have been covered: Static magnetic field and glucose metabolism, static magnetic field and vitamins and the role of vitamins on glucose metabolism. Considering these articles comprehensively, the conclusions are as follows: The primary cause of changes in cells after incubation in external SMF is disruption of free radical metabolism and elevation of their concentration. Such disruption causes oxidative stress leading to an unsteadiness of glucose level and insulin release. Moreover, based on available data, it was concluded that exposure to SMF alters plasma levels of vitamin A, C, D and E; these parameters can take part in disorder of glucose homeostasis and insulin release.

  14. The UPR reduces glucose metabolism via IRE1 signaling.

    Science.gov (United States)

    van der Harg, Judith M; van Heest, Jessica C; Bangel, Fabian N; Patiwael, Sanne; van Weering, Jan R T; Scheper, Wiep

    2017-04-01

    Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis. Since the UPR is strategically positioned to sense and integrate metabolic stress signals, it is likely that - apart from its adaptive response to restore proteostasis - it also directly affects metabolic pathways. Here we investigate the direct role of the UPR in glucose homeostasis. O-GlcNAc is a post-translational modification that is highly responsive to glucose fluctuations. We find that UPR activation results in decreased O-GlcNAc modification, in line with reduced glucose metabolism. Our data indicate that UPR activation has no direct impact on the upstream processes in glucose metabolism; glucose transporter expression, glucose uptake and hexokinase activity. In contrast, prolonged UPR activation decreases glycolysis and mitochondrial metabolism. Decreased mitochondrial respiration is not accompanied by apoptosis or a structural change in mitochondria indicating that the reduction in metabolic rate upon UPR activation is a physiological non-apoptotic response. Metabolic decrease is prevented if the IRE1 pathway of the UPR is inhibited. This indicates that activation of IRE1 signaling induces a reduction in glucose metabolism, as part of an adaptive response. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. PET-imaging of cerebral glucose metabolism during sleep and dreaming

    International Nuclear Information System (INIS)

    Heiss, W.D.; Pawlik, G.; Herholz, K.; Wagner, R.; Wienhard, K.

    1985-01-01

    Positron emission tomography (PET) of ( 18 F)-2-fluoro-2-deoxyglucose (FDG) affording non-invasive repeatable quantification of local cerebral glucose utilization was employed to determine possible differential effects of sleep, with and without dreaming, on regional brain metabolism of normal volunteers also measured during wakefulness. (author). 7 refs.; 1 tab

  16. A Major Role for Perifornical Orexin Neurons in the Control of Glucose Metabolism in Rats

    NARCIS (Netherlands)

    Yi, Chun-Xia; Serlie, Mireille J.; Ackermans, Mariette T.; Foppen, Ewout; Buijs, Ruud M.; Sauerwein, Hans P.; Fliers, Eric; Kalsbeek, Andries

    2009-01-01

    OBJECTIVE-The hypothalamic neuropeptide orexin influences (feeding) behavior as well as energy metabolism. Administration of exogenous orexin-A into the brain has been shown to increase both food intake and blood glucose levels. In the present study, we investigated the role of endogenous

  17. Dynamic Functional Imaging of Brain Glucose Utilization using fPET-FDG

    Science.gov (United States)

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

    2014-01-01

    Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis is straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism. PMID:24936683

  18. Cerebral glucose metabolism change in patients with complex regional pain syndrome. A PET study

    International Nuclear Information System (INIS)

    Shiraishi, Satoe; Kobayashi, Hidetoshi; Nihashi, Takashi

    2006-01-01

    The aim of this study was to examine abnormalities of the central nervous system in patients with chronic pain who were diagnosed with complex regional pain syndrome (CRPS). Brain activity was assessed using 18 F-fluorodeoxyglucose positron emission tomography. The data collected from 18 patients were compared with data obtained from 13 normal age-matched controls. Our results showed that glucose metabolism was bilaterally increased in the secondary somatosensory cortex, mid-anterior cingulated cortex (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior parietal cortex (PPC), and cerebellum as well as in the right posterior insula and right thalamus in our patients. In contrast, glucose metabolism was reduced contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which correlated with pain duration. These data suggested that glucose metabolism in the brains of patients with CRPS changes dramatically at each location. In particular, glucose metabolism was increased in the areas concerned with somatosensory perception, possibly due to continuous painful stimulation. (author)

  19. Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

    Science.gov (United States)

    McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

  20. Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury

    OpenAIRE

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

    2017-01-01

    Abstract Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET). We consecutively enrolled 11 patients with FOG after HIBI. The patients’ overall brain metabolism was measured by F-18 FDG PET, and we co...

  1. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

    Science.gov (United States)

    Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

    2016-05-05

    High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  3. A positron emission tomography analysis of glucose metabolism in Alzheimer's disease brain using [F-18] fluorodeoxyglucose : A parallel study with elemental concentrations

    NARCIS (Netherlands)

    Cutts, DA; Spyrou, NM; Maguire, RP; Stedman, JD; Leenders, KL

    Alzheimer's disease (AD) isa debilitating form of dementia which leads to impaired memory, thinking and behavior. This work examines elemental concentrations between "normal" and AD subjects as well as the hemispherical differences within the brain. Tissue samples from both hemispheres of the

  4. At the centennial of Michaelis and Menten, competing Michaelis-Menten steps explain effect of GLP-1 on blood-brain transfer and metabolism of glucose

    DEFF Research Database (Denmark)

    Jensen, Michael Gejl; Rungby, Jørgen; Brock, Birgitte

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with pancreatic and extrapancreatic effects. Studies reveal significant effects in regions of brain tissue that regulate appetite and satiety. The effects cause that mimetics of GLP-1 serves as treatment of type 2 diabete...

  5. N-3 fatty acids, neuronal activity and energy metabolism in the brain

    Directory of Open Access Journals (Sweden)

    Harbeby Emilie

    2012-07-01

    Full Text Available The content of docosahexaenoic acid (DHA in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1 a lower brain glucose utilization, 2 a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3 a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

  6. Electroacupuncture Treatment Improves Learning-Memory Ability and Brain Glucose Metabolism in a Mouse Model of Alzheimer’s Disease: Using Morris Water Maze and Micro-PET

    Directory of Open Access Journals (Sweden)

    Jing Jiang

    2015-01-01

    Full Text Available Introduction. Alzheimer’s disease (AD causes progressive hippocampus dysfunctions leading to the impairment of learning and memory ability and low level of uptake rate of glucose in hippocampus. What is more, there is no effective treatment for AD. In this study, we evaluated the beneficial and protective effects of electroacupuncture in senescence-accelerated mouse prone 8 (SAMP8. Method. In the electroacupuncture paradigm, electroacupuncture treatment was performed once a day for 15 days on 7.5-month-old SAMP8 male mice. In the normal control paradigm and AD control group, 7.5-month-old SAMR1 male mice and SAMP8 male mice were grabbed and bandaged while electroacupuncture group therapy, in order to ensure the same treatment conditions, once a day, 15 days. Results. From the Morris water maze (MWM test, we found that the treatment of electroacupuncture can improve the spatial learning and memory ability of SAMP8 mouse, and from the micro-PET test, we proved that after the electroacupuncture treatment the level of uptake rate of glucose in hippocampus was higher than normal control group. Conclusion. These results suggest that the treatment of electroacupuncture may provide a viable treatment option for AD.

  7. Regional glucose metabolism using PETT in normal and psychiatric populations

    Energy Technology Data Exchange (ETDEWEB)

    Brodie, J.D.; Wolf, A.P.; Volkow, N.

    1982-01-01

    The metabolism of /sup 18/F-2-deoxy-2-fluoro-D-glucose (/sup 18/FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed.

  8. Adult glucose metabolism in extremely birthweight-discordant monozygotic twins

    DEFF Research Database (Denmark)

    Frost, M; Petersen, I; Brixen, K

    2012-01-01

    Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment....

  9. Regional glucose metabolism using PETT in normal and psychiatric populations

    International Nuclear Information System (INIS)

    Brodie, J.D.; Wolf, A.P.; Volkow, N.

    1982-01-01

    The metabolism of 18 F-2-deoxy-2-fluoro-D-glucose ( 18 FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed

  10. Renal glucose metabolism in normal physiological conditions and in diabetes.

    Science.gov (United States)

    Alsahli, Mazen; Gerich, John E

    2017-11-01

    The kidney plays an important role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate. After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis. In this post-absorptive state, the kidneys utilize about 10% of all glucose utilized by the body. After glucose ingestion, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release in the postprandial period. Each day, the kidneys filter approximately 180g of glucose and virtually all of this is reabsorbed into the circulation. Hormones (most importantly insulin and catecholamines), substrates, enzymes, and glucose transporters are some of the various factors influencing the kidney's role. Patients with type 2 diabetes have an increased renal glucose uptake and release in the fasting and the post-prandial states. Additionally, glucosuria in these patients does not occur at plasma glucose levels that would normally produce glucosuria in healthy individuals. The major abnormality of renal glucose metabolism in type 1 diabetes appears to be impaired renal glucose release during hypoglycemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Glucose metabolism transporters and epilepsy: only GLUT1 has an established role.

    Science.gov (United States)

    Hildebrand, Michael S; Damiano, John A; Mullen, Saul A; Bellows, Susannah T; Oliver, Karen L; Dahl, Hans-Henrik M; Scheffer, Ingrid E; Berkovic, Samuel F

    2014-02-01

    The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy-causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  12. The regulation of cerebral glucose uptake and metabolism in normal and diabetic man

    International Nuclear Information System (INIS)

    Polonsky, K.

    1987-01-01

    The effects of changes in serum insulin and glucose on brain glucose metabolism using PET technology were investigated. Eight normal, right-handed, male subjects were studied on three separate occasions at least one week apart. In each subject a PET scan was performed under three different metabolic circumstances: basal conditions after an overnight fast, euglycemic clamp, and hypoglycemic clamp in which the plasma glucose was maintained at 55 mg/dl. Exogenous insulin was infused at the same rate in the euglycemic and hypoglycemic clamp studies. In the latter study, the concomitant glucose infusion rate was reduced to allow the plasma glucose concentration to fall to the desired level of mild hypoglycemia. During each study, dynamic positron emission tomography was used to characterize cerebral uptake and distribution of the Fluorine-18 2-deoxyglucose radiotracer as a function of time. Analysis of the brain uptake curve and tracer input function provided rate constants for transport and phosphorylation in accord with a 3 compartmental model (Sokoloff, 1979). Dynamic scans were performed on each study occasion allowing individual rate constants to be studied. In addition to the brain uptake curves, plasma glucose, F-18 2DG levels and counterregulatory hormone values were determined from frequent arterialized venous blood samples

  13. TXNIP regulates peripheral glucose metabolism in humans

    DEFF Research Database (Denmark)

    Parikh, Hemang; Carlsson, Emma; Chutkow, William A

    2007-01-01

    combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated...... expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP regulates both insulin-dependent and insulin......-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM....

  14. Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

    Science.gov (United States)

    Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

    2017-06-01

    Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

  15. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    Science.gov (United States)

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost Munk; Tvede, Michael

    2013-01-01

    and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

  17. Utilization of dietary glucose in the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Alemany Marià

    2011-10-01

    Full Text Available Abstract This review is focused on the fate of dietary glucose under conditions of chronically high energy (largely fat intake, evolving into the metabolic syndrome. We are adapted to carbohydrate-rich diets similar to those of our ancestors. Glucose is the main energy staple, but fats are our main energy reserves. Starvation drastically reduces glucose availability, forcing the body to shift to fatty acids as main energy substrate, sparing glucose and amino acids. We are not prepared for excess dietary energy, our main defenses being decreased food intake and increased energy expenditure, largely enhanced metabolic activity and thermogenesis. High lipid availability is a powerful factor decreasing glucose and amino acid oxidation. Present-day diets are often hyperenergetic, high on lipids, with abundant protein and limited amounts of starchy carbohydrates. Dietary lipids favor their metabolic processing, saving glucose, which additionally spares amino acids. The glucose excess elicits hyperinsulinemia, which may derive, in the end, into insulin resistance. The available systems of energy disposal could not cope with the excess of substrates, since they are geared for saving not for spendthrift, which results in an unbearable overload of the storage mechanisms. Adipose tissue is the last energy sink, it has to store the energy that cannot be used otherwise. However, adipose tissue growth also has limits, and the excess of energy induces inflammation, helped by the ineffective intervention of the immune system. However, even under this acute situation, the excess of glucose remains, favoring its final conversion to fat. The sum of inflammatory signals and deranged substrate handling induce most of the metabolic syndrome traits: insulin resistance, obesity, diabetes, liver steatosis, hyperlipidemia and their compounded combined effects. Thus, a maintained excess of energy in the diet may result in difficulties in the disposal of glucose, eliciting

  18. Brain glucose content in fetuses of ethanol-fed rats

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  19. Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes*

    Science.gov (United States)

    Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

    2013-01-01

    Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID:24240094

  20. Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes.

    Science.gov (United States)

    Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

    2013-12-27

    Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance.

  1. Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.

    Science.gov (United States)

    Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan

    2008-02-01

    Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, Pobese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

  2. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    International Nuclear Information System (INIS)

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-01-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism

  3. Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

    International Nuclear Information System (INIS)

    Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

    1989-01-01

    Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using 18 F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences

  4. Brain glucose sensing, counterregulation, and energy homeostasis.

    Science.gov (United States)

    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  5. Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury: A pilot study.

    Science.gov (United States)

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

    2017-11-01

    Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET).We consecutively enrolled 11 patients with FOG after HIBI. The patients' overall brain metabolism was measured by F-18 FDG PET, and we compared their regional brain metabolic activity with that from 15 healthy controls using a voxel-by-voxel-based statistical mapping analysis. Additionally, we correlated each patient's FOG severity with the brain metabolism using a covariance analysis.Patients with FOG had significantly decreased brain glucose metabolism in the midbrain, bilateral thalamus, bilateral cingulate gyri, right supramarginal gyrus, right angular gyrus, right paracentral lobule, and left precentral gyrus (PFDR-corrected brain metabolism were noted in patients with FOG. The covariance analysis identified significant correlations between the FOG severity and the brain metabolism in the right lingual gyrus, left fusiform gyrus, and bilateral cerebellar crus I (Puncorrected brain regions in the gait-related neural network, including the cerebral cortex, subcortical structures, brainstem, and cerebellum, may significantly contribute to the development of FOG in HIBI. Moreover, the FOG severity may be associated with the visual cortex and cerebellar regions.

  6. Impaired brain energy gain upon a glucose load in obesity.

    Science.gov (United States)

    Wardzinski, Ewelina K; Kistenmacher, Alina; Melchert, Uwe H; Jauch-Chara, Kamila; Oltmanns, Kerstin M

    2018-03-06

    There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31 phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity. Copyright © 2018. Published by Elsevier Inc.

  7. The effects of hypoglycin on glucose metabolism in the rat

    International Nuclear Information System (INIS)

    Osmundsen, H.; Billington, D.; Taylor, J.R.; Sherratt, H.S.A.

    1978-01-01

    The kinetics of glucose metabolism were evaluated in rats deprived of food 15 to 21 h after the administration of hypoglycaemic doses of hypoglycin (100 mg/kg body wt.) by following changes in the specific radioactivities of 14 C and 3 H in blood glucose after an intravenous dose of [U- 14 C,2- 3 H]glucose. During this time, recycling of glucose through the Cori cycle was virtually abolished, the rate of irreversible disposal of glucose and its total body mass were both decreased by about 70%, whereas there was little effect on the mean transit time for glucose. It was concluded that hypoglycaemia is due to inhibition of gluconeogenesis. (author)

  8. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    International Nuclear Information System (INIS)

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr.; Gillin, J.C.

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep

  9. Brain Ceramide Metabolism in the Control of Energy Balance

    Directory of Open Access Journals (Sweden)

    Céline Cruciani-Guglielmacci

    2017-10-01

    Full Text Available The regulation of energy balance by the central nervous system (CNS is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D. Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate, the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance.

  10. Is cerebral glucose metabolism related to blood-brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?: A 18F-FDG PET/CT study.

    Science.gov (United States)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Ursini, Francesco; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Toniolo, Sofia; Di Pietro, Barbara; Motta, Caterina; Schillaci, Orazio

    2016-09-01

    The aim of this study was to investigate the relationships between blood-brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(F) fluoro-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects.

  11. Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

    Science.gov (United States)

    Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

    1998-11-01

    Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

  12. Metabolism of tritiated D-glucose in rat erythrocytes

    International Nuclear Information System (INIS)

    Manuel y Keenoy, B.; Malaisse-Lagae, F.; Malaisse, W.J.

    1991-01-01

    The metabolism of D-[U-14C]glucose, D-[1-14C]glucose, D-[6-14C]glucose, D-[1-3H]glucose, D-[2-3H]glucose, D-[3-3H]glucose, D-[3,4-3H]glucose, D-[5-3H]glucose, and D-[6-3H]glucose was examined in rat erythrocytes. There was a fair agreement between the rate of 3HOH production from either D-[3-3H]glucose and D-[5-3H]glucose, the decrease in the 2,3-diphosphoglycerate pool, its fractional turnover rate, the production of 14C-labeled lactate from D-[U-14C]glucose, and the total lactate output. The generation of both 3HOH and tritiated acidic metabolites from D-[3,4-3H]glucose indicated incomplete detritiation of the C4 during interconversion of fructose-1,6-bisphosphate and triose phosphates. Erythrocytes unexpectedly generated 3HOH from D-[6-3H]glucose, a phenomenon possibly attributable to the detritiation of [3-3H]pyruvate in the reaction catalyzed by glutamate pyruvate transaminase. The production of 3HOH from D-[2-3H]glucose was lower than that from D-[5-3H]glucose, suggesting enzyme-to-enzyme tunneling of glycolytic intermediates in the hexokinase/phosphoglucoisomerase/phosphofructokinase sequence. The production of 3HOH from D-[1-3H]glucose largely exceeded that of 14CO2 from D-[1-14C]glucose, a situation tentatively ascribed to the generation of 3HOH in the phosphomannoisomerase reaction. It is further speculated that the adjustment in specific radioactivity of D-[1-3H]glucose-6-phosphate cannot simultaneously match the vastly different degrees of isotopic discrimination in velocity at the levels of the reactions catalyzed by either glucose-6-phosphate dehydrogenase or phosphoglucoisomerase. The interpretation of the present findings thus raises a number of questions, which are proposed as a scope for further investigations

  13. A link between sleep loss, glucose metabolism and adipokines

    Directory of Open Access Journals (Sweden)

    H.G. Padilha

    2011-10-01

    Full Text Available The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

  14. Glucose metabolism in cultured trophoblasts from human placenta

    International Nuclear Information System (INIS)

    Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H.

    1990-01-01

    The development of appropriate placental trophoblast isolation and culture techniques enables the study of pathways of glucose utilization by this important cell layer in vitro. Trophoblasts from normal term placentas were isolated and cultured 24 hours and 72 hours in uncoated polystyrene culture tubes or tubes previously coated with a fibrin matrix. Trophoblasts cultured on fibrin are morphologically distinct from those cultured on plastic or other matrices and generally resemble in vivo syncytium. Cells were incubated up to 3 hours with 14 C-labeled glucose and reactions were stopped by addition of perchloric acid. 14 CO 2 production by trophoblasts increased linearly with time however the largest accumulation of label was in organic acids. Trophoblasts cultured in absence of fibrin utilized more glucose and accumulated more 14 C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO 2 by the phosphogluconate (PG) pathway was estimated from specific yields of 14 CO 2 from [1- 14 C]-D-glucose and [6- 14 C]-D-glucose. Approximately 6% of glucose oxidation was by the PG pathway when cells were cultured on fibrin compared to approximately 1% by cells cultured in the absence of fibrin. The presence of a fibrin growth matrix appears to modulate the metabolism of glucose by trophoblast from human placenta in vitro

  15. Enhanced muscle glucose metabolism after exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Garetto, L P; Goodman, M N

    1984-01-01

    Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the pr......Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase...... in the stimulated leg closely mimicked that observed previously after voluntary exercise on a treadmill. With no insulin added to the perfusate, glucose incorporation into glycogen was markedly enhanced in muscles that were glycogen depleted as were the uptake of 2-deoxyglucose and 3-O-methylglucose. Likewise......, the stimulation of these processes by insulin was enhanced and continued to be so 2 h later when the muscles of the stimulated leg had substantially repleted their glycogen stores. The results suggest that the increases in insulin-mediated glucose utilization and glycogen synthesis in muscle after exercise...

  16. Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study.

    Science.gov (United States)

    Park, So Hyeon; Park, Hyun Soo; Kim, Sang Eun

    2016-08-01

    Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after (18)F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders.

  17. Higher transport and metabolism of glucose in astrocytes compared with neurons: a multiphoton study of hippocampal and cerebellar tissue slices.

    Science.gov (United States)

    Jakoby, Patrick; Schmidt, Elke; Ruminot, Iván; Gutiérrez, Robin; Barros, L Felipe; Deitmer, Joachim W

    2014-01-01

    Glucose is the most important energy substrate for the brain, and its cellular distribution is a subject of great current interest. We have employed fluorescent glucose probes, the 2-deoxy-D-glucose derivates 6- and 2-([N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose) (2-NBDG), to measure transport and metabolism of glucose in acute slices of mouse hippocampus and cerebellum. In the hippocampus, 6-NBDG, which is not metabolized and hence indicates glucose transport, was taken up faster in astrocyte-rich layers (Stratum radiatum [S.r.], Stratum oriens [S.o.]) than in pyramidal cells. Metabolizable 2-NBDG showed larger signals in S.r. and S.o. than in Stratum pyramidale, suggesting faster glucose utilization rate in the astrocyte versus the neuronal compartment. Similarly, we found higher uptake and temperature-sensitive metabolism of 2-NBDG in Bergmann glia when compared with adjacent Purkinje neurons of cerebellar slices. A comparison between 6-NBDG transport and glucose transport in cultured cells using a fluorescence resonance energy transfer nanosensor showed that relative to glucose, 6-NBDG is transported better by neurons than by astrocytes. These results indicate that the preferential transport and metabolism of glucose by glial cells versus neurons proposed for the hippocampus and cerebellum by ourselves (in vitro) and for the barrel cortex by Chuquet et al. (in vivo) is more pronounced than anticipated.

  18. The ketogenic diet: metabolic influences on brain excitability and epilepsy

    Science.gov (United States)

    Lutas, Andrew; Yellen, Gary

    2012-01-01

    A dietary therapy for pediatric epilepsy known as the ketogenic diet has seen a revival in its clinical use in the past decade. Though the diet’s underlying mechanism remains unknown, modern scientific approaches like genetic disruption of glucose metabolism are allowing for more detailed questions to be addressed. Recent work indicates that several mechanisms may exist for the ketogenic diet including disruption of glutamatergic synaptic transmission, inhibition of glycolysis, and activation of ATP-sensitive potassium channels. Here we describe on-going work in these areas that is providing a better understanding of metabolic influences on brain excitability and epilepsy. PMID:23228828

  19. Enteral nutrition increases interstitial brain glucose levels in poor-grade subarachnoid hemorrhage patients.

    Science.gov (United States)

    Kofler, Mario; Schiefecker, Alois J; Beer, Ronny; Gaasch, Maxime; Rhomberg, Paul; Stover, John; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

    2018-03-01

    Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition. Sixty-three interventions were analyzed. The mean amount of EN per intervention was 472.4 ± 10.7 kcal. CMD-glucose levels significantly increased from 1.59 ± 0.13 mmol/l at baseline to a maximum of 2.03 ± 0.2 mmol/l after 5 h (p  40) and the microdialysis probe location. The increase in CMD-glucose was directly dependent on the magnitude of increase of serum glucose levels (p = 0.007). No change in CMD-lactate, CMD-pyruvate, CMD-LPR, or CMD-glutamate (p > 0.4) was observed. Routine EN also increased CMD-glucose even if baseline concentrations were critically low ( < 0.7 mmol/l, neuroglucopenia; p < 0.001). These results may have treatment implications regarding glucose management of poor-grade aneurysmal SAH patients.

  20. Glucose metabolic alterations in hippocampus of diabetes mellitus rats and the regulation of aerobic exercise.

    Science.gov (United States)

    Li, Jingjing; Liu, Beibei; Cai, Ming; Lin, Xiaojing; Lou, Shujie

    2017-11-04

    Diabetes could negatively affect the structures and functions of the brain, especially could cause the hippocampal dysfunction, however, the potential metabolic mechanism is unclear. The aim of this study was to investigate the changes of glucose metabolism in hippocampus of diabetes mellitus rats and the regulation of aerobic exercise, and to analyze the possible mechanisms. A rat model of type 2 diabetes mellitus was established by high-fat diet feeding in combination with STZ intraperitoneal injection, then 4 weeks of aerobic exercise was conducted. The glucose metabolites and key enzymes involved in glucose metabolism in hippocampus were respectively detected by GC/MS based metabolomics and western blot. Metabolomics results showed that compared with control rats, the level of citric acid was significantly decreased, while the levels of lactic acid, ribose 5-phosphate, xylulose 5-phosphate and glucitol were significantly increased in the diabetic rat. Compared with diabetic rats, the level of citric acid was significantly increased, while the lactic acid, ribose 5-phosphate and xylulose 5-phosphate were significantly decreased in the diabetic exercise rats. Western blot results showed that lower level of citrate synthase and oxoglutarate dehydrogenase, higher level of aldose reductase and glucose 6-phosphatedehydrogenase were found in the diabetic rats when compared to control rats. After 4 weeks of aerobic exercise, citrate synthase was upregulated and glucose 6-phosphatedehydrogenase was downregulated in the diabetic rats. These results suggest that diabetes could cause abnormal glucose metabolism, and aerobic exercise plays an important role in regulating diabetes-induced disorder of glucose metabolism in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Leptin and the central nervous system control of glucose metabolism.

    Science.gov (United States)

    Morton, Gregory J; Schwartz, Michael W

    2011-04-01

    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

  2. TCPTP Regulates Insulin Signalling in AgRP Neurons to Coordinate Glucose Metabolism with Feeding.

    Science.gov (United States)

    Dodd, Garron T; Lee-Young, Robert S; Brüning, Jens C; Tiganis, Tony

    2018-04-30

    Insulin regulates glucose metabolism by eliciting effects on peripheral tissues as well as the brain. Insulin receptor (IR) signalling inhibits AgRP-expressing neurons in the hypothalamus to contribute to the suppression of hepatic glucose production (HGP) by insulin, whereas AgRP neuronal activation attenuates brown adipose tissue (BAT) glucose uptake. The tyrosine phosphatase TCPTP suppresses IR signalling in AgRP neurons. Hypothalamic TCPTP is induced by fasting and degraded after feeding. Here we assessed the influence of TCPTP in AgRP neurons in the control of glucose metabolism. TCPTP deletion in AgRP neurons ( Agrp -Cre; Ptpn2 fl/fl ) enhanced insulin sensitivity as assessed by the increased glucose infusion rates and reduced HGP during hyperinsulinemic-euglycemic clamps, accompanied by increased [ 14 C]-2-deoxy-D-glucose uptake in BAT and browned white adipose tissue. TCPTP deficiency in AgRP neurons promoted the intracerebroventricular insulin-induced repression of hepatic gluconeogenesis in otherwise unresponsive food-restricted mice yet had no effect in fed/satiated mice where hypothalamic TCPTP levels are reduced. The improvement in glucose homeostasis in Agrp -Cre; Ptpn2 fl/fl mice was corrected by IR heterozygosity ( Agrp -Cre; Ptpn2 fl/fl ; Insr fl/+ ), causally linking the effects on glucose metabolism with the IR signalling in AgRP neurons. Our findings demonstrate that TCPTP controls IR signalling in AgRP neurons to coordinate HGP and brown/beige adipocyte glucose uptake in response to feeding/fasting. © 2018 by the American Diabetes Association.

  3. Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2008-04-01

    Full Text Available The use of stimulants (methylphenidate and amphetamine as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations given with and without methylphenidate (20 mg, oral. Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less. This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing" of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering or impaired (i.e., attention deficit hyperactivity disorder, but it could be detrimental when

  4. The metabolism of malate by cultured rat brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, M.C.; Tildon, J.T.; Couto, R.; Stevenson, J.H.; Caprio, F.J. (Department of Pediatrics, University of Maryland School of Medicine, Baltimore (USA))

    1990-12-01

    Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-(U-14C)malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain.

  5. Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance.

    Science.gov (United States)

    Li, Weiping; Li, Qifu

    2012-01-01

    To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, PPCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, PPCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m². In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m² indicated impaired β cell function in PCOS women with normal glucose tolerance.

  6. Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

    Science.gov (United States)

    Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

    2012-01-01

    Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

  7. Antilipolytic drug boosts glucose metabolism in prostate cancer

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Divilov, Vadim; Koziorowski, Jacek

    2013-01-01

    The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts.......The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts....

  8. Glucose metabolic patterns in neurodegenerative brain diseases

    NARCIS (Netherlands)

    Teune, Laura Klaaske

    2013-01-01

    Neurodegeneratieve hersenziekten zoals de ziekte van Parkinson (PD), multisysteem atrofie (MSA), progressieve supranucleaire parese (PSP) zijn hersenaandoeningen waarbij langzamerhand – over vele jaren - de zenuwcellen in bepaalde gebieden verloren gaan. In de klinische praktijk kan het lastig zijn

  9. Gastric emptying, glucose metabolism and gut hormones

    DEFF Research Database (Denmark)

    Vermeulen, Mechteld A R; Richir, Milan C; Garretsen, Martijn K

    2011-01-01

    To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant and carb......To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant...... and carbohydrate content. However, gastric emptying of fluids is influenced by its nutrient composition; hence, safety of preoperative carbohydrate loading should be confirmed. Because gut hormones link carbohydrate metabolism and gastric emptying, hormonal responses were studied....

  10. Cooperation between brain and islet in glucose homeostasis and diabetes

    Science.gov (United States)

    Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

    2014-01-01

    Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

  11. Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2018-05-01

    Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

  12. Glucose metabolism in critically ill patients

    DEFF Research Database (Denmark)

    Nielsen, Signe Tellerup; Krogh-Madsen, Rikke; Møller, Kirsten

    2015-01-01

    glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar......, stimulates insulin secretion and inhibits glucagon release both in healthy individuals and in patients with type 2 diabetes (T2DM). Compared to insulin, GLP-1 appears to be associated with a lower risk of severe hypoglycemia, probably because the magnitude of its insulinotropic action is dependent on blood...

  13. Intermittent metabolic switching, neuroplasticity and brain health

    Science.gov (United States)

    Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

    2018-01-01

    During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

  14. Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism

    International Nuclear Information System (INIS)

    Harrell, L.E.; Davis, J.N.

    1984-01-01

    Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-[ 3 H]glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity

  15. Changes of regional cerebral glucose metabolism in normal aging process : A study with FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Joon Kee; Kim, Sang Eun; Lee, Kyung Han; Choi, Yong; Choe, Yearn Seong; Kim, Byung Tae [Sungkyunkwan Univ., School of Medicine, Seoul (Korea, Republic of)

    2001-08-01

    Normal aging results in detectable changes in the brain structure and function. We evaluated the changes of regional cerebral glucose metabolism in the normal aging process with FDG PET. Brain PET images were obtained in 44 healthy volunteers (age range 20-69'y'; M:F = 29:15) who had no history of neuropsychiatric disorders. On 6 representative transaxial images, ROls were drawn in the cortical and subcortical areas. Regional FDG uptake was normalized using whole brain uptake to adjust for the injection dose and correct for nonspecific declines of glucose metabolism affecting all brain areas equally. In the prefrontal, temporoparietal and primary sensorimotor cortex, the normalized FDG uptake (NFU) reached a peak In subjects in their 30s. The NFU in the prefrontal and primary sensorimotor cortex declined with age after 30s at a rate of 3.15%/decade and 1.93%/decade, respectively. However, the NFU in the lernporoparietal cortex did not change significantly with age after 30s. The anterior (prefrontal) posterior (temporoparietal) gradient peaked in subjects in their 30s and declined with age the reafter at a rate of 35%/decade. The NFU in the caudate nucleus was decreased with age after 20s at a rate of 2.39%/decade. In the primary visual cortex, putamen, and thalamus, the NFU values did not change significantly throughout the ages covered. These patterns were not significantly different between right and left cerebral hemispheres. Of interest was that the NFU in the left cerebellar cortex was increased with age after 20s at a rate of 2.86%/decade. These data demonstrate regional variation of the age-related changes in the cerebral glucose metabolism, with the most prominent age-related decline of metabolism in the prefrontal cortex. The increase in the cerebellar metabolism with age might reflect a process of neuronal plasticity associated with aging.

  16. Changes of regional cerebral glucose metabolism in normal aging process : A study with FDG PET

    International Nuclear Information System (INIS)

    Yoon, Joon Kee; Kim, Sang Eun; Lee, Kyung Han; Choi, Yong; Choe, Yearn Seong; Kim, Byung Tae

    2001-01-01

    Normal aging results in detectable changes in the brain structure and function. We evaluated the changes of regional cerebral glucose metabolism in the normal aging process with FDG PET. Brain PET images were obtained in 44 healthy volunteers (age range 20-69'y'; M:F = 29:15) who had no history of neuropsychiatric disorders. On 6 representative transaxial images, ROls were drawn in the cortical and subcortical areas. Regional FDG uptake was normalized using whole brain uptake to adjust for the injection dose and correct for nonspecific declines of glucose metabolism affecting all brain areas equally. In the prefrontal, temporoparietal and primary sensorimotor cortex, the normalized FDG uptake (NFU) reached a peak In subjects in their 30s. The NFU in the prefrontal and primary sensorimotor cortex declined with age after 30s at a rate of 3.15%/decade and 1.93%/decade, respectively. However, the NFU in the lernporoparietal cortex did not change significantly with age after 30s. The anterior (prefrontal) posterior (temporoparietal) gradient peaked in subjects in their 30s and declined with age the reafter at a rate of 35%/decade. The NFU in the caudate nucleus was decreased with age after 20s at a rate of 2.39%/decade. In the primary visual cortex, putamen, and thalamus, the NFU values did not change significantly throughout the ages covered. These patterns were not significantly different between right and left cerebral hemispheres. Of interest was that the NFU in the left cerebellar cortex was increased with age after 20s at a rate of 2.86%/decade. These data demonstrate regional variation of the age-related changes in the cerebral glucose metabolism, with the most prominent age-related decline of metabolism in the prefrontal cortex. The increase in the cerebellar metabolism with age might reflect a process of neuronal plasticity associated with aging

  17. Brain, nutrition and metabolism : Studies in lean, obese and insulin resistant humans

    NARCIS (Netherlands)

    Versteeg, R.I.

    2017-01-01

    This thesis describes studies on the effects of obesity, weight loss and meal timing on the human brain and glucose metabolism. We investigated effects of meal timing during a hypocaloric diet and weight loss on brain serotonin transporters (SERT) and dopamine transporters (DAT), neuronal activity

  18. Lactate storm marks cerebral metabolism following brain trauma.

    Science.gov (United States)

    Lama, Sanju; Auer, Roland N; Tyson, Randy; Gallagher, Clare N; Tomanek, Boguslaw; Sutherland, Garnette R

    2014-07-18

    Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2011-01-01

    Full Text Available Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine and control group. Fasting blood glucose (FBG, weight, total cholesterol (TC, triglyceride (TG, high-density lipoprotein-cholesterol (HDL-c, low-density lipoprotein-cholesterol (LDL-c, and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT was performed. RT2 PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC, fasting serum insulin (FINS, homeostasis model assessment insulin resistance (HOMA-IR index, TC, and TG, compared with those of control group. RT2 profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4, mitogen-activated protein kinase 14 (MAPK14, MAPK8(c-jun N-terminal kinase, JNK, peroxisome proliferator-activated receptor α (PPARα, uncoupling protein 2 (UCP2, and hepatic nuclear factor 4α(HNF4α, whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP, PPARγ coactivator 1α(PGC 1α, and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK- p38 MAPK-GLUT4, JNK pathway, and PPARα pathway.

  20. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  1. Enhanced muscle glucose metabolism after exercise in the rat

    DEFF Research Database (Denmark)

    Garetto, L P; Richter, Erik; Goodman, M N

    1984-01-01

    glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity......Thirty minutes after a treadmill run, glucose utilization and glycogen synthesis in perfused rat skeletal muscle are enhanced due to an increase in insulin sensitivity (Richter et al., J. Clin. Invest. 69: 785-793, 1982). The exercise used in these studies was of moderate intensity, and muscle...... was still observed in perfused muscle; however, glucose utilization was also increased in the absence of added insulin (1.5 vs. 4.2 mumol X g-1 X h-1). In contrast 2.5 h after the run, muscle glycogen had returned to near preexercise values, and only the insulin-induced increase in glucose utilization...

  2. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

    Science.gov (United States)

    Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

    2016-04-01

    Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder.

    Science.gov (United States)

    Saito, Tomoyuki; Tamura, Maasa; Chiba, Yuhei; Katsuse, Omi; Suda, Akira; Kamada, Ayuko; Ikura, Takahiro; Abe, Kie; Ogawa, Matsuyoshi; Minegishi, Kaoru; Yoshimi, Ryusuke; Kirino, Yohei; Ihata, Atsushi; Hirayasu, Yoshio

    2017-08-15

    Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    International Nuclear Information System (INIS)

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8±0.75 y, 5 IGAs: male, 22.6±2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA

  5. Effects of kinins on glucose metabolism in vivo.

    Science.gov (United States)

    Hartl, W H; Jauch, K W; Wolfe, R R; Schildberg, F W

    1990-01-01

    Current concepts of the physiological importance of the kinin/prostaglandin system view these tissue factors as part of a defense system, which protects tissues from potentially noxious factors, such as hypoxia or destructive inflammatory reactions. This kinin-triggered defense reaction includes an improvement in cellular energy metabolism. The latter is brought about in peripheral tissues by an increased availability of glucose for anaerobic and aerobic glycolysis, whereas in liver tissue, energy-consuming reactions such as gluconeogenesis are attenuated. There is evidence that such favorable effects can also be produced in man when kinins are administered systemically. Prostaglandins are most likely the second messengers of kinin-induced metabolic effects. Thus, it may be advantageous to increase the availability of kinins either by exogenous infusion or by inhibiting endogenous degradation during postoperative stress or in diseases such as diabetes mellitus, in which glucose metabolism is severely disturbed.

  6. Glucose Metabolism from Mouth to Muscle: A Student Experiment to Teach Glucose Metabolism during Exercise and Rest

    Science.gov (United States)

    Engeroff, Tobias; Fleckenstein, Johannes; Banzer, Winfried

    2017-01-01

    We developed an experiment to help students understand basic regulation of postabsorptive and postprandial glucose metabolism and the availability of energy sources for physical activity in the fed and fasted state. Within a practical session, teams of two or three students (1 subject and 1 or 2 investigators) performed one of three different…

  7. Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Rougemont, D; Baron, J C; Collard, P; Bustany, P; Comar, D; Agid, Y

    1983-06-01

    Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and /sup 18/F-Fluoro-2-deoxy-D-glucose (/sup 18/FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain.

  8. Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

    International Nuclear Information System (INIS)

    Rougemont, D.; Baron, J.C.; Collard, P.; Bustany, P.; Comar, D.; Agid, Y.

    1983-06-01

    Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and 18 F-Fluoro-2-deoxy-D-glucose ( 18 FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain

  9. Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation

    DEFF Research Database (Denmark)

    Madsen, P L; Hasselbalch, S G; Hagemann, L P

    1995-01-01

    fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic......Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety......-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation...

  10. Glucose metabolism during rotational shift-work in healthcare workers.

    Science.gov (United States)

    Sharma, Anu; Laurenti, Marcello C; Dalla Man, Chiara; Varghese, Ron T; Cobelli, Claudio; Rizza, Robert A; Matveyenko, Aleksey; Vella, Adrian

    2017-08-01

    Shift-work is associated with circadian rhythm disruption and an increased risk of obesity and type 2 diabetes. We sought to determine the effect of rotational shift-work on glucose metabolism in humans. We studied 12 otherwise healthy nurses performing rotational shift-work using a randomised crossover study design. On each occasion, participants underwent an isotope-labelled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model. We sought to determine differences in fasting and postprandial glucose metabolism during the day shift vs the night shift. Postprandial glycaemic excursion was higher during the night shift (381±33 vs 580±48 mmol/l per 5 h, pshift. While insulin action did not differ between study days, the beta cell responsivity to glucose (59±5 vs 44±4 × 10 -9  min -1 ; pshift. Impaired beta cell function during the night shift may result from normal circadian variation, the effect of rotational shift-work or a combination of both. As a consequence, higher postprandial glucose concentrations are observed during the night shift.

  11. Timing of potential and metabolic brain energy

    DEFF Research Database (Denmark)

    Korf, Jakob; Gramsbergen, Jan Bert

    2007-01-01

    functions. We introduce the concepts of potential and metabolic brain energy to distinguish trans-membrane gradients of ions or neurotransmitters and the capacity to generate energy from intra- or extra-cerebral substrates, respectively. Higher brain functions, such as memory retrieval, speaking......The temporal relationship between cerebral electro-physiological activities, higher brain functions and brain energy metabolism is reviewed. The duration of action potentials and transmission through glutamate and GABA are most often less than 5 ms. Subjects may perform complex psycho......-physiological tasks within 50 to 200 ms, and perception of conscious experience requires 0.5 to 2 s. Activation of cerebral oxygen consumption starts after at least 100 ms and increases of local blood flow become maximal after about 1 s. Current imaging technologies are unable to detect rapid physiological brain...

  12. Brain docosahexaenoic acid uptake and metabolism.

    Science.gov (United States)

    Lacombe, R J Scott; Chouinard-Watkins, Raphaël; Bazinet, Richard P

    2018-02-08

    Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the brain where it serves to regulate several important processes and, in addition, serves as a precursor to bioactive mediators. Given that the capacity of the brain to synthesize DHA locally is appreciably low, the uptake of DHA from circulating lipid pools is essential to maintaining homeostatic levels. Although, several plasma pools have been proposed to supply the brain with DHA, recent evidence suggests non-esterified-DHA and lysophosphatidylcholine-DHA are the primary sources. The uptake of DHA into the brain appears to be regulated by a number of complementary pathways associated with the activation and metabolism of DHA, and may provide mechanisms for enrichment of DHA within the brain. Following entry into the brain, DHA is esterified into and recycled amongst membrane phospholipids contributing the distribution of DHA in brain phospholipids. During neurotransmission and following brain injury, DHA is released from membrane phospholipids and converted to bioactive mediators which regulate signaling pathways important to synaptogenesis, cell survival, and neuroinflammation, and may be relevant to treating neurological diseases. In the present review, we provide a comprehensive overview of brain DHA metabolism, encompassing many of the pathways and key enzymatic regulators governing brain DHA uptake and metabolism. In addition, we focus on the release of non-esterified DHA and subsequent production of bioactive mediators and the evidence of their proposed activity within the brain. We also provide a brief review of the evidence from post-mortem brain analyses investigating DHA levels in the context of neurological disease and mood disorder, highlighting the current disparities within the field. Copyright © 2017. Published by Elsevier Ltd.

  13. Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

    Science.gov (United States)

    Perneczky, R; Drzezga, A; Diehl-Schmid, J; Schmid, G; Wohlschläger, A; Kars, S; Grimmer, T; Wagenpfeil, S; Monsch, A; Kurz, A

    2006-09-01

    Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

  14. Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

    Science.gov (United States)

    Glenn, Thomas C; Martin, Neil A; McArthur, David L; Hovda, David A; Vespa, Paul; Johnson, Matthew L; Horning, Michael A; Brooks, George A

    2015-06-01

    We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

  15. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease

    NARCIS (Netherlands)

    Lammers, Nicolette M.; Sondermeijer, Brigitte M.; Twickler, Th B. Marcel; de Bie, Rob M.; Ackermans, Mariëtte T.; Fliers, Eric; Schuurman, P. Richard; la Fleur, Susanne E.; Serlie, Mireille J.

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry,

  16. T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain.

    Science.gov (United States)

    Paech, Daniel; Schuenke, Patrick; Koehler, Christina; Windschuh, Johannes; Mundiyanapurath, Sibu; Bickelhaupt, Sebastian; Bonekamp, David; Bäumer, Philipp; Bachert, Peter; Ladd, Mark E; Bendszus, Martin; Wick, Wolfgang; Unterberg, Andreas; Schlemmer, Heinz-Peter; Zaiss, Moritz; Radbruch, Alexander

    2017-12-01

    Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.

  17. Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

    Science.gov (United States)

    Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

    2017-05-01

    Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Glucose transporter of the human brain and blood-brain barrier

    International Nuclear Information System (INIS)

    Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.

    1988-01-01

    We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species

  19. Effect of ezetimibe on lipid and glucose metabolism after a fat and glucose load.

    Science.gov (United States)

    Hiramitsu, Shinya; Miyagishima, Kenji; Ishii, Junichi; Matsui, Shigeru; Naruse, Hiroyuki; Shiino, Kenji; Kitagawa, Fumihiko; Ozaki, Yukio

    2012-11-01

    The clinical benefit of ezetimibe, an intestinal cholesterol transporter inhibitor, for treatment of postprandial hyperlipidemia was assessed in subjects who ingested a high-fat and high-glucose test meal to mimic westernized diet. We enrolled 20 male volunteers who had at least one of the following: waist circumference ≥ 85 cm, body mass index ≥ 25 kg/m(2), or triglycerides (TG) from 150 to 400mg/dL. After 4 weeks of treatment with ezetimibe (10mg/day), the subjects ingested a high-fat and high-glucose meal. Then changes in serum lipid and glucose levels were monitored after 0, 2, 4, and 6h, and the area under the curve (AUC) was calculated for the change in each parameter. At 4 and 6h postprandially, TG levels were decreased (pAUC for TG was also decreased (pAUC for apo-B48 was also significantly decreased (pBlood glucose and insulin levels at 2h postprandially were significantly decreased by ezetimibe (pAUCs for blood glucose and insulin were also significantly decreased (pglucose metabolism, this drug is likely to be beneficial for dyslipidemia in patients with postprandial metabolic abnormalities. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  20. Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18

    International Nuclear Information System (INIS)

    Baxter, L.R. Jr.; Phelps, M.E.; Mazziotta, J.C.; Schwartz, J.M.; Gerner, R.H.; Selin, C.E.; Sumida, R.M.

    1985-01-01

    Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression

  1. Cerebral glucose metabolic differences in patients with panic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M. (NIMH, Bethesda, MD (USA))

    1990-08-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer (F-18)-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.

  2. Cerebral glucose metabolic differences in patients with panic disorder

    International Nuclear Information System (INIS)

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M.

    1990-01-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task

  3. Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors...

  4. Implications of Resveratrol on Glucose Uptake and Metabolism

    Directory of Open Access Journals (Sweden)

    David León

    2017-03-01

    Full Text Available Resveratrol—a polyphenol of natural origin—has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for medical applications including cancer and type 2 diabetes. Here, we review the latest advances in understanding how resveratrol modulates glucose uptake, regulates cellular metabolism, and how this may be useful to improve current therapies. We discuss challenges and findings regarding the inhibition of glucose uptake by resveratrol and other polyphenols of similar chemical structure. We review alternatives that can be exploited to improve cancer therapies, including the use of other polyphenols, or the combination of resveratrol with other molecules and their impact on glucose homeostasis in cancer and diabetes.

  5. Glucose metabolism from mouth to muscle: a student experiment to teach glucose metabolism during exercise and rest.

    Science.gov (United States)

    Engeroff, Tobias; Fleckenstein, Johannes; Banzer, Winfried

    2017-03-01

    We developed an experiment to help students understand basic regulation of postabsorptive and postprandial glucose metabolism and the availability of energy sources for physical activity in the fed and fasted state. Within a practical session, teams of two or three students (1 subject and 1 or 2 investigators) performed one of three different trials: 1) inactive, in which subjects ingested a glucose solution (75 g in 300 ml of water) and rested in the seated position until the end of the trial; 2) prior activity, in which the subject performed 15 min of walking before glucose ingestion and a subsequent resting phase; and 3) postactivity, in which the subject ingested glucose solution, walked (15 min), and rested afterwards. Glucose levels were drawn before trials (fasting value), immediately after glucose ingestion (0 min), and 5, 10, 15, 20, 25, 30, 40, 50, and 60 min thereafter. Students analyzed glucose values and worked on 12 tasks. Students evaluated the usefulness of the experiment; 54.2% of students found the experiment useful to enable them to gain a further understanding of the learning objectives and to clarify items, and 44.1% indicated that the experiment was necessary to enable them to understand the learning objectives. For 6.8% the experiment was not necessary but helpful to check what they had learned, and 3.4% found that the experiment was not necessary. The present article shows the great value of experiments within practical courses to help students gain knowledge of energy metabolism. Using an active learning strategy, students outworked complex physiological tasks and improved beneficial communication and interaction between students with different skill sets and problem-solving strategies. Copyright © 2017 the American Physiological Society.

  6. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael

    2013-01-01

    and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism.......New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota...

  7. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael

    2013-01-01

    New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota...... and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

  8. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies.

    Science.gov (United States)

    Greene, Amanda E; Todorova, Mariana T; Seyfried, Thomas N

    2003-08-01

    Brain cells are metabolically flexible because they can derive energy from both glucose and ketone bodies (acetoacetate and beta-hydroxybutyrate). Metabolic control theory applies principles of bioenergetics and genome flexibility to the management of complex phenotypic traits. Epilepsy is a complex brain disorder involving excessive, synchronous, abnormal electrical firing patterns of neurons. We propose that many epilepsies with varied etiologies may ultimately involve disruptions of brain energy homeostasis and are potentially manageable through principles of metabolic control theory. This control involves moderate shifts in the availability of brain energy metabolites (glucose and ketone bodies) that alter energy metabolism through glycolysis and the tricarboxylic acid cycle, respectively. These shifts produce adjustments in gene-linked metabolic networks that manage or control the seizure disorder despite the continued presence of the inherited or acquired factors responsible for the epilepsy. This hypothesis is supported by information on the management of seizures with diets including fasting, the ketogenic diet and caloric restriction. A better understanding of the compensatory genetic and neurochemical networks of brain energy metabolism may produce novel antiepileptic therapies that are more effective and biologically friendly than those currently available.

  10. Proton Transport Chains in Glucose Metabolism: Mind the Proton

    Directory of Open Access Journals (Sweden)

    Dirk Roosterman

    2018-06-01

    Full Text Available The Embden–Meyerhof–Parnas (EMP pathway comprises eleven cytosolic enzymes interacting to metabolize glucose to lactic acid [CH3CH(OHCOOH]. Glycolysis is largely considered as the conversion of glucose to pyruvate (CH3COCOO-. We consider glycolysis to be a cellular process and as such, transporters mediating glucose uptake and lactic acid release and enable the flow of metabolites through the cell, must be considered as part of the EMP pathway. In this review, we consider the flow of metabolites to be coupled to a flow of energy that is irreversible and sufficient to form ordered structures. This latter principle is highlighted by discussing that lactate dehydrogenase (LDH complexes irreversibly reduce pyruvate/H+ to lactate [CH3CH(OHCOO-], or irreversibly catalyze the opposite reaction, oxidation of lactate to pyruvate/H+. However, both LDH complexes are considered to be driven by postulated proton transport chains. Metabolism of glucose to two lactic acids is introduced as a unidirectional, continuously flowing pathway. In an organism, cell membrane-located proton-linked monocarboxylate transporters catalyze the final step of glycolysis, the release of lactic acid. Consequently, both pyruvate and lactate are discussed as intermediate products of glycolysis and substrates of regulated crosscuts of the glycolytic flow.

  11. The Lin28/let-7 axis regulates glucose metabolism

    Science.gov (United States)

    Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

    2012-01-01

    SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

  12. Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer’s disease

    Science.gov (United States)

    Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

    2016-01-01

    Abstract See Hansson and Gouras (doi:10.1093/aww146) for a scientific commentary on this article. Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer’s disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer’s disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer’s disease-related hypometabolism. Nine healthy young adults (age range: 20–30), 96 cognitively normal older adults (age range: 61–96), and 20 patients with Alzheimer’s disease (age range: 50–90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P glucose metabolism regions defined in young adults (T = 2.05, P glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose

  13. Regional differences of relationships between atrophy and glucose metabolism of cerebral cortex in patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    Toyama, H.; Uemura, K.; Kanekiyo, S.; Ishii, K.; Ishii, K.

    2002-01-01

    Aim: The purpose of this paper is to estimate a correlation between the extent of atrophy and the decline in the brain function measured with PET study among the patients with Alzheimer's disease by each brain lobe. Materials and Methods: Two groups, the normal controls (male: 8, female: 22 age: 62.4±4.9) and the patients with Alzheimer's disease (male: 6, female: 24, age: 65.9±7.2) participated in this study. The extent of atrophy was evaluated from the extracted gyrus on 2D-projection magnetic resonance imaging (MRI) and the cerebral cortical glucose metabolism was assessed on 2D-projection positron emission tomography (PET) image, and then a relationship between the cerebral atrophy and the function was evaluated by each brain lobe extracted automatically. 2D-projection of PET and MR images were made by means of the Mollweide method which keeps the area of the brain surface. In order to extract brain lobes from each subject automatically, the bitmap with different value by each brain lobe was made from a standard brain image and was automatically transformed to match each subject's brain image by using SPM99. A correlation image was generated between 2D-projection images of glucose metabolism and the area of the sulcus and the gyrus extracted from the correlation between MR and PET images clustered by K-means method. Results: The glucose metabolism of Alzheimer's disease was lower than that of normal control subjects at the frontal, parietal, and temporal lobes with the same extent of atrophy as that of the normal. There was high correlation between the area of gyrus and the glucose metabolism, and the correlation tendency of the Alzheimer's disease was steeper than that of the normal control at the parietal lobe. Conclusions: Combined analysis of regional morphology and function may be useful to distinguish pathological process such as early stage of Alzheimer's disease from normal physiological aging

  14. Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency.

    Science.gov (United States)

    Akman, Cigdem Inan; Provenzano, Frank; Wang, Dong; Engelstad, Kristin; Hinton, Veronica; Yu, Julia; Tikofsky, Ronald; Ichese, Masonari; De Vivo, Darryl C

    2015-02-01

    (18)F fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) facilitates examination of glucose metabolism. Previously, we described regional cerebral glucose hypometabolism using (18)F FDG-PET in patients with Glucose transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in Glut1 DS using quantitative image analysis to identify the epileptic network based on the regional distribution of glucose hypometabolism. (18)F FDG-PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using Statistical parametric Mapping (SPM). Summed images were preprocessed for statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest (ROI) analysis was performed to validate SPM results. Visual analysis of the (18)F FDG-PET images demonstrated prominent regional glucose hypometabolism in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison using SPM analysis confirmed that the regional distribution of glucose hypo-metabolism was present in thalamus, cerebellum, temporal cortex and central lobule. Two mildly affected patients without epilepsy had hypometabolism in cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose hypometabolism did not correlate with age at the time of PET imaging, head circumference, CSF glucose concentration at the time of diagnosis, RBC glucose uptake, or CNS score. Quantitative analysis of (18)F FDG-PET imaging in Glut1 DS patients confirmed that hypometabolism was present symmetrically in thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus correlated with the clinical history of epilepsy. Copyright © 2014. Published by Elsevier B.V.

  15. Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry.

    Science.gov (United States)

    Sheng, Zhenyu; Santiago, Ammy M; Thomas, Mark P; Routh, Vanessa H

    2014-09-01

    Lateral hypothalamic area (LHA) orexin neurons modulate reward-based feeding by activating ventral tegmental area (VTA) dopamine (DA) neurons. We hypothesize that signals of peripheral energy status influence reward-based feeding by modulating the glucose sensitivity of LHA orexin glucose-inhibited (GI) neurons. This hypothesis was tested using electrophysiological recordings of LHA orexin-GI neurons in brain slices from 4 to 6week old male mice whose orexin neurons express green fluorescent protein (GFP) or putative VTA-DA neurons from C57Bl/6 mice. Low glucose directly activated ~60% of LHA orexin-GFP neurons in both whole cell and cell attached recordings. Leptin indirectly reduced and ghrelin directly enhanced the activation of LHA orexin-GI neurons by glucose decreases from 2.5 to 0.1mM by 53±12% (n=16, Pglucose sensitivity. Fasting increased activation of LHA orexin-GI neurons by decreased glucose, as would be predicted by these hormonal effects. We also evaluated putative VTA-DA neurons in a novel horizontal slice preparation containing the LHA and VTA. Decreased glucose increased the frequency of spontaneous excitatory post-synaptic currents (sEPSCs; 125 ± 40%, n=9, Pneurons. sEPSCs were completely blocked by AMPA and NMDA glutamate receptor antagonists (CNQX 20 μM, n=4; APV 20μM, n=4; respectively), demonstrating that these sEPSCs were mediated by glutamatergic transmission onto VTA DA neurons. Orexin-1 but not 2 receptor antagonism with SB334867 (10μM; n=9) and TCS-OX2-29 (2μM; n=5), respectively, blocks the effects of decreased glucose on VTA DA neurons. Thus, decreased glucose increases orexin-dependent excitatory glutamate neurotransmission onto VTA DA neurons. These data suggest that the glucose sensitivity of LHA orexin-GI neurons links metabolic state and reward-based feeding. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Regulatory cascade of neuronal loss and glucose metabolism.

    Science.gov (United States)

    Hassan, Mubashir; Sehgal, Sheikh A; Rashid, Sajid

    2014-01-01

    During recent years, numerous lines of research including proteomics and molecular biology have highlighted multiple targets and signaling pathways involved in metabolic abnormalities and neurodegeneration. However, correlation studies of individual neurodegenerative disorders (ND) including Alzheimer, Parkinson, Huntington and Amyotrophic lateral sclerosis in association with Diabetes type 2 Mellitus (D2M) are demanding tasks. Here, we report a comprehensive mechanistic overview of major contributors involved in process-based co-regulation of D2M and NDs. D2M is linked with Alzheimer's disease through deregulation of calcium ions thereby leading to metabolic fluctuations of glucose and insulin. Parkinson-associated proteins disturb insulin level through ATP-sensitive potassium ion channels and extracellular signal-regulated kinases to enhance glucose level. Similarly, proteins which perturb carbohydrate metabolism for disturbing glucose homeostasis link Huntington, Amyotrophic lateral sclerosis and D2M. Other misleading processes which interconnect D2M and NDs include oxidative stress, mitochondrial dysfunctions and microRNAs (miRNA29a/b and miRNA-9). Overall, the collective listing of pathway-specific targets would help in establishing novel connections between NDs and D2M to explore better therapeutic interventions.

  17. Metabolic drift in the aging brain.

    Science.gov (United States)

    Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

    2016-05-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

  18. Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

    Science.gov (United States)

    Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

    2018-03-12

    Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

  19. Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans

    DEFF Research Database (Denmark)

    Lerche, Susanne; Brock, Birgitte; Rungby, Jørgen

    2008-01-01

    OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested......-independent effect of GLP-1 on unidirectional glucose transport into the brain during a pituitary-pancreatic normoglycemic (plasma glucose approximately 4.5 mmol/l) clamp with 18-fluoro-deoxy-glucose as tracer. RESULTS: On average, GLP-1 reduced cerebral glucose transport by 27% in total cerebral gray matter (P = 0...... that a hormone involved in postprandial glucose regulation also limits glucose delivery to brain tissue and hence provides a possible regulatory mechanism for the link between plasma glucose and brain glucose. Because GLP-1 reduces glucose uptake across the intact blood-brain barrier at normal glycemia, GLP-1...

  20. Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

    Science.gov (United States)

    Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

    2016-04-01

    We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Effects of intermittent fasting on glucose and lipid metabolism.

    Science.gov (United States)

    Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

    2017-08-01

    Two intermittent fasting variants, intermittent energy restriction (IER) and time-restricted feeding (TRF), have received considerable interest as strategies for weight-management and/or improving metabolic health. With these strategies, the pattern of energy restriction and/or timing of food intake are altered so that individuals undergo frequently repeated periods of fasting. This review provides a commentary on the rodent and human literature, specifically focusing on the effects of IER and TRF on glucose and lipid metabolism. For IER, there is a growing evidence demonstrating its benefits on glucose and lipid homeostasis in the short-to-medium term; however, more long-term safety studies are required. Whilst the metabolic benefits of TRF appear quite profound in rodents, findings from the few human studies have been mixed. There is some suggestion that the metabolic changes elicited by these approaches can occur in the absence of energy restriction, and in the context of IER, may be distinct from those observed following similar weight-loss achieved via modest continuous energy restriction. Mechanistically, the frequently repeated prolonged fasting intervals may favour preferential reduction of ectopic fat, beneficially modulate aspects of adipose tissue physiology/morphology, and may also impinge on circadian clock regulation. However, mechanistic evidence is largely limited to findings from rodent studies, thus necessitating focused human studies, which also incorporate more dynamic assessments of glucose and lipid metabolism. Ultimately, much remains to be learned about intermittent fasting (in its various forms); however, the findings to date serve to highlight promising avenues for future research.

  2. The action of piracetam on 14C-glucose metabolism in normal and posthypoxic rat cerebral cortex slices

    International Nuclear Information System (INIS)

    Domanska-Janik, K.; Zaleska, M.

    1977-01-01

    The stimulating effect of piracetam on the respiration and glycolysis was observed in rat brain cortex slices incubated under oxygen atmosphere. After preincubation of the slices under pure nitrogen atmosphere, piracetam influenced also decarboxylation of the C 1 -glucose carbon, indicating stimulation of the pentose cycle. Any significant effect of piracetam on the lowered by anoxia incorporation of 14 C from U- 14 C-glucose into macromolecular fractions was not observed. The results have supported a protective effect of piracetam against oxygen deficiency, caused mainly by stimulation of metabolic glucose pathways, connected with energy production in CNS. (author)

  3. Brain lactate metabolism in humans with subarachnoid hemorrhage.

    Science.gov (United States)

    Oddo, Mauro; Levine, Joshua M; Frangos, Suzanne; Maloney-Wilensky, Eileen; Carrera, Emmanuel; Daniel, Roy T; Levivier, Marc; Magistretti, Pierre J; LeRoux, Peter D

    2012-05-01

    Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) 119 μmol/L) versus nonhyperglycolytic. Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

  4. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    Science.gov (United States)

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.; Fidler, Isaiah J.; Cantley, Lewis C.; Locasale, Jason W.; Weihua, Zhang

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the non-oxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBPs) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis, and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. PMID:25511375

  5. Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

    Science.gov (United States)

    Selwyn, Reed; Hockenbury, Nicole; Jaiswal, Shalini; Mathur, Sanjeev; Armstrong, Regina C; Byrnes, Kimberly R

    2013-12-01

    Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

  6. Relation of periodontitis and metabolic syndrome with gestational glucose metabolism disorder.

    Science.gov (United States)

    Bullon, Pedro; Jaramillo, Reyes; Santos-Garcia, Rocio; Rios-Santos, Vicente; Ramirez, Maria; Fernandez-Palacin, Ana; Fernandez-Riejos, Patricia

    2014-02-01

    Gestational diabetes mellitus (GDM) and metabolic syndrome have been related to periodontitis. This study's objective is to establish the relationship between them in pregnant women affected by gestational glucose metabolism disorder. In 188 pregnant women with positive O'Sullivan test (POT) results, an oral glucose tolerance test (OGTT) was performed to diagnose GDM. The mother's periodontal parameters, age, prepregnancy weight and height and body mass index (BMI), blood pressure, gestational age, and birth weight were recorded at 24 to 28 weeks of pregnancy, as well as levels of glucose, C-reactive protein, triglycerides, glycated hemoglobin (HbA1c), and total, low-density lipoprotein, high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL) cholesterol levels. Prepregnancy weight, prepregnancy BMI, systolic and diastolic blood pressure, VLDL cholesterol, and glucose parameters were higher in GDM compared with POT (P periodontitis than in patients without periodontitis (P c, triglycerides, and 1- and 2-hour OGTT were positively related with probing depth and clinical attachment level; blood glucose was related only to bleeding on probing (P c, basal OGTT, and 1- and 2-hour OGTT were positively related to prepregnancy BMI and blood pressure; HDL cholesterol was negatively related to prepregnancy BMI; C-reactive protein was positively related to prepregnancy BMI and diastolic blood pressure (P periodontal disease and some biochemical parameters such as lipid and glucose data in pregnancy, and also among metabolic syndrome and biochemical parameters.

  7. Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and motor function.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available SIRT1 plays crucial roles in glucose and lipid metabolism, and has various functions in different tissues including brain. The brain-specific SIRT1 knockout mice display defects in somatotropic signaling, memory and synaptic plasticity. And the female mice without SIRT1 in POMC neuron are more sensitive to diet-induced obesity. Here we created transgenic mice overexpressing SIRT1 in striatum and hippocampus under the control of CaMKIIα promoter. These mice, especially females, exhibited increased fat accumulation accompanied by significant upregulation of adipogenic genes in white adipose tissue. Glucose tolerance of the mice was also impaired with decreased Glut4 mRNA levels in muscle. Moreover, the SIRT1 overexpressing mice showed decreased energy expenditure, and concomitantly mitochondria-related genes were decreased in muscle. In addition, these mice showed unusual spontaneous physical activity pattern, decreased activity in open field and rotarod performance. Further studies demonstrated that SIRT1 deacetylated IRS-2, and upregulated phosphorylation level of IRS-2 and ERK1/2 in striatum. Meanwhile, the neurotransmitter signaling in striatum and the expression of endocrine hormones in hypothalamus and serum T3, T4 levels were altered. Taken together, our findings demonstrate that SIRT1 in forebrain regulates lipid/glucose metabolism and motor function.

  8. Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization

    International Nuclear Information System (INIS)

    Blomqvist, G.; Widen, L.; Hellstrand, E.; Gutniak, M.; Grill, V.

    1991-01-01

    The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using D-glucose 11 C(ul) as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62±19 (mean±SEM) μmol hg -1 min -1 , and the half-saturation constant was found to be 4.1±3.2 mM. (orig.)

  9. Trajectories of BMI change impact glucose and insulin metabolism.

    Science.gov (United States)

    Walsh, E I; Shaw, J; Cherbuin, N

    2018-03-01

    The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m 2 ) trajectory over twelve years with plasma insulin (μlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier

  10. Metabolic changes in the brain

    International Nuclear Information System (INIS)

    Meermann, H.

    1982-01-01

    A positron emission tomograph (PET) is described for displaying the flow pattern of radioactive isotope-labelled substances injected into the human brain. This is claimed to assist in diagnosis of circulation disturbances and to show sugar and oxygen uptake. Emitted gamma rays are detected by rings of 96 detectors whose outputs are used to produce a computer-generated reproduction of the brain, with different colours or densities on a cathode ray tube representing concentration of the labelled substance. Epileptic spasms, Huntington's chorea and drug uptake, as well as albumen content variations due to tumours, are stated to be capable of display. Future uses of the ''PET'' tomograph are discussed. (G.M.E.)

  11. Microbial Regulation of Glucose Metabolism and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Silke Crommen

    2017-12-01

    Full Text Available Type 2 diabetes is a combined disease, resulting from a hyperglycemia and peripheral and hepatic insulin resistance. Recent data suggest that the gut microbiota is involved in diabetes development, altering metabolic processes including glucose and fatty acid metabolism. Thus, type 2 diabetes patients show a microbial dysbiosis, with reduced butyrate-producing bacteria and elevated potential pathogens compared to metabolically healthy individuals. Furthermore, probiotics are a known tool to modulate the microbiota, having a therapeutic potential. Current literature will be discussed to elucidate the complex interaction of gut microbiota, intestinal permeability and inflammation leading to peripheral and hepatic insulin resistance. Therefore, this review aims to generate a deeper understanding of the underlying mechanism of potential microbial strains, which can be used as probiotics.

  12. [Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

    Science.gov (United States)

    Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

    To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

  13. The Role of Circulating Amino Acids in the Hypothalamic Regulation of Liver Glucose Metabolism.

    Science.gov (United States)

    Arrieta-Cruz, Isabel; Gutiérrez-Juárez, Roger

    2016-07-01

    A pandemic of diabetes and obesity has been developing worldwide in close association with excessive nutrient intake and a sedentary lifestyle. Variations in the protein content of the diet have a direct impact on glucose homeostasis because amino acids (AAs) are powerful modulators of insulin action. In this work we review our recent findings on how elevations in the concentration of the circulating AAs leucine and proline activate a metabolic mechanism located in the mediobasal hypothalamus of the brain that sends a signal to the liver via the vagus nerve, which curtails glucose output. This neurogenic signal is strictly dependent on the metabolism of leucine and proline to acetyl-coenzyme A (CoA) and the subsequent production of malonyl-CoA; the signal also requires functional neuronal ATP-sensitive potassium channels. The liver then responds by lowering the rate of gluconeogenesis and glycogenolysis, ultimately leading to a net decrease in glucose production and in concentrations of circulating glucose. Furthermore, we review here how our work with proline suggests a new role of astrocytes in the central regulation of glycemia. Last, we outline how factors such as the consumption of fat-rich diets can interfere with glucoregulatory mechanisms and, in the long term, may contribute to the development of hyperglycemia, a hallmark of type 2 diabetes. © 2016 American Society for Nutrition.

  14. The Role of Circulating Amino Acids in the Hypothalamic Regulation of Liver Glucose Metabolism123

    Science.gov (United States)

    Arrieta-Cruz, Isabel; Gutiérrez-Juárez, Roger

    2016-01-01

    A pandemic of diabetes and obesity has been developing worldwide in close association with excessive nutrient intake and a sedentary lifestyle. Variations in the protein content of the diet have a direct impact on glucose homeostasis because amino acids (AAs) are powerful modulators of insulin action. In this work we review our recent findings on how elevations in the concentration of the circulating AAs leucine and proline activate a metabolic mechanism located in the mediobasal hypothalamus of the brain that sends a signal to the liver via the vagus nerve, which curtails glucose output. This neurogenic signal is strictly dependent on the metabolism of leucine and proline to acetyl-coenzyme A (CoA) and the subsequent production of malonyl-CoA; the signal also requires functional neuronal ATP-sensitive potassium channels. The liver then responds by lowering the rate of gluconeogenesis and glycogenolysis, ultimately leading to a net decrease in glucose production and in concentrations of circulating glucose. Furthermore, we review here how our work with proline suggests a new role of astrocytes in the central regulation of glycemia. Last, we outline how factors such as the consumption of fat-rich diets can interfere with glucoregulatory mechanisms and, in the long term, may contribute to the development of hyperglycemia, a hallmark of type 2 diabetes. PMID:27422516

  15. Non-invasive measurement of brain glycogen by NMR spectroscopy and its application to the study of brain metabolism

    Science.gov (United States)

    Tesfaye, Nolawit; Seaquist, Elizabeth R.; Öz, Gülin

    2011-01-01

    Glycogen is the reservoir for glucose in the brain. Beyond the general agreement that glycogen serves as an energy source in the central nervous system, its exact role in brain energy metabolism has yet to be elucidated. Experiments performed in cell and tissue culture and animals have shown that glycogen content is affected by several factors including glucose, insulin, neurotransmitters, and neuronal activation. The study of in vivo glycogen metabolism has been hindered by the inability to measure glycogen non-invasively, but in the past several years, the development of a non-invasive localized 13C nuclear magnetic resonance (NMR) spectroscopy method has enabled the study of glycogen metabolism in the conscious human. With this technique, 13C-glucose is administered intravenously and its incorporation into and wash-out from brain glycogen is tracked. One application of this method has been to the study of brain glycogen metabolism in humans during hypoglycemia: data have shown that mobilization of brain glycogen is augmented during hypoglycemia and, after a single episode of hypoglycemia, glycogen synthesis rate is increased, suggesting that glycogen stores rebound to levels greater than baseline. Such studies suggest glycogen may serve as a potential energy reservoir in hypoglycemia and may participate in the brain's adaptation to recurrent hypoglycemia and eventual development of hypoglycemia unawareness. Beyond this focused area of study, 13C NMR spectroscopy has a broad potential for application in the study of brain glycogen metabolism and carries the promise of a better understanding of the role of brain glycogen in diabetes and other conditions. PMID:21732401

  16. Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucos Metabolism

    International Nuclear Information System (INIS)

    Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Vaska, P.; Fowler, J.S.; Telang, F.; Alexoff, D.; Logan, J.; Wong, C.

    2011-01-01

    The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with ( 18 F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes ('on' condition) and once with both cell phones deactivated ('off' condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm 3 ) and P < .05 (corrected for multiple comparisons) were considered significant. Brain glucose metabolism computed as absolute metabolism ((micro)mol/100 g per minute) and as normalized metabolism (region/whole brain). Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 (micro)mol/100 g per minute; mean difference, 2.4 (95% confidence interval, 0.67-4.2); P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001). In healthy participants and compared with no exposure, 50-minute cell phone

  17. Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae*

    Science.gov (United States)

    Medeiros, Rychelle Clayde Affonso; Girardi, Karina do Carmo de Vasconcelos; Cardoso, Fernanda Karlla Luz; Mietto, Bruno de Siqueira; Pinto, Thiago Gomes de Toledo; Gomez, Lilian Sales; Rodrigues, Luciana Silva; Gandini, Mariana; Amaral, Julio Jablonski; Antunes, Sérgio Luiz Gomes; Corte-Real, Suzana; Rosa, Patricia Sammarco; Pessolani, Maria Cristina Vidal; Nery, José Augusto da Costa; Sarno, Euzenir Nunes; Batista-Silva, Leonardo Ribeiro; Sola-Penna, Mauro; Oliveira, Marcus Fernandes; Moraes, Milton Ozório; Lara, Flavio Alves

    2016-01-01

    Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed. PMID:27555322

  18. Selective reductions in prefrontal glucose metabolism in murderers.

    Science.gov (United States)

    Raine, A; Buchsbaum, M S; Stanley, J; Lottenberg, S; Abel, L; Stoddard, J

    1994-09-15

    This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.

  19. Disruption of behavior and brain metabolism in artificially reared rats.

    Science.gov (United States)

    Aguirre-Benítez, Elsa L; Porras, Mercedes G; Parra, Leticia; González-Ríos, Jacquelina; Garduño-Torres, Dafne F; Albores-García, Damaris; Avendaño, Arturo; Ávila-Rodríguez, Miguel A; Melo, Angel I; Jiménez-Estrada, Ismael; Mendoza-Garrido, Ma Eugenia; Toriz, César; Diaz, Daniel; Ibarra-Coronado, Elizabeth; Mendoza-Ángeles, Karina; Hernández-Falcón, Jesús

    2017-12-01

    Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[ 18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017. © 2017 Wiley Periodicals, Inc.

  20. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease. Copyright © 2017 Endocrine Society

  1. Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Masayuki; Ichiya, Yuichi; Hosokawa, Shinichi; Otsuka, Makoto; Kuwabara, Yasuo; Fukumura, Toshimitsu; Kato, Motohiro; Goto, Ikuo; Masuda, Kouji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1992-11-01

    By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia. (author).

  2. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Morphological and glucose metabolism abnormalities in alcoholic Korsakoff's syndrome: group comparisons and individual analyses.

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    Anne-Lise Pitel

    Full Text Available BACKGROUND: Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS. Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. METHODOLOGY/PRINCIPAL FINDINGS: Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and (18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. CONCLUSIONS/SIGNIFICANCE: These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker.

  4. Dietary carbohydrates and glucose metabolism in diabetic patients.

    Science.gov (United States)

    Parillo, M; Riccardi, G

    1995-12-01

    Dietary carbohydrates represent one of the major sources of energy for the human body. However, the main (if not the only) therapy for diabetes since ancient times has been based on reducing dietary carbohydrates drastically because of their effects on blood glucose levels. The introduction of insulin in the 1920s and then of oral hypoglycaemic drugs led to various studies evaluating the biochemical characteristics of carbohydrates and their effects on glucose metabolism in diabetic patients. This review considers the role of dietary carbohydrates in the diet of diabetic patients in the light of the most recent studies and provides a short summary of the biochemistry of carbohydrates and the physiology of carbohydrate digestion.

  5. Effect of abomasal glucose infusion on splanchnic and whole-body glucose metabolism in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism.......Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism....

  6. Regional cerebral glucose metabolism in frontotemporal lobar degeneration

    International Nuclear Information System (INIS)

    Park, J.M.; Cho, S.S.; Lee, K.-H.; Choi, Y.; Choe, Y.S.; Kim, B.-T.; Kim, S.E.; Kwon, J.C.; Na, D.L.

    2002-01-01

    Purpose: Frontotemporal lobar degeneration (FTLD) is the third most common cause of dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neuro behavioral syndromes can be produced by FTLD: frontotemporal dementia (FTD), frontotemporal dementia with motor neuron disease (MND), semantic dementia (SD), and progressive aphasia (PA). We investigated patterns of metabolic impairment in patients with FTLD presented with four different clinical syndromes. Methods: We analyzed glucose metabolic patterns on FDG PET images obtained from 34 patients with a clinical diagnosis of FTLD (19 FTD, 6 MND, 6 SD, and 3 PA, according to a consensus criteria for clinical syndromes associated with FTLD) and 7 age-matched healthy controls using SPM99. Results: Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral pre-motor area was shown in patients with MND. Patients with SD had metabolic deficit in the left posterior temporal cortex including Wernicke's area, while hypometabolism in the bilateral inferior frontal gyrus including Broca's area and left angular gyrus was seen in patients with PA. These metabolic patterns were well correlated with clinical and neuropsychological features of FTLD syndromes. Conclusion: These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD

  7. Glucose metabolism regulates T cell activation, differentiation and functions

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    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  8. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

    NARCIS (Netherlands)

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose

  9. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

    Science.gov (United States)

    Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

    2008-11-01

    Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

  10. Metabolic profile of normal glucose-tolerant subjects with elevated 1-h plasma glucose values

    Directory of Open Access Journals (Sweden)

    Thyparambil Aravindakshan Pramodkumar

    2016-01-01

    Full Text Available Aim: The aim of this study was to compare the metabolic profiles of subjects with normal glucose tolerance (NGT with and without elevated 1-h postglucose (1HrPG values during an oral glucose tolerance test (OGTT. Methodology: The study group comprised 996 subjects without known diabetes seen at tertiary diabetes center between 2010 and 2014. NGT was defined as fasting plasma glucose <100 mg/dl (5.5 mmol/L and 2-h plasma glucose <140 mg/dl (7.8 mmol/L after an 82.5 g oral glucose (equivalent to 75 g of anhydrous glucose OGTT. Anthropometric measurements and biochemical investigations were done using standardized methods. The prevalence rate of generalized and central obesity, hypertension, dyslipidemia, and metabolic syndrome (MS was determined among the NGT subjects stratified based on their 1HrPG values as <143 mg/dl, ≥143-<155 mg/dl, and ≥155 mg/dl, after adjusting for age, sex, body mass index (BMI, waist circumference, alcohol consumption, smoking, and family history of diabetes. Results: The mean age of the 996 NGT subjects was 48 ± 12 years and 53.5% were male. The mean glycated hemoglobin for subjects with 1HrPG <143 mg/dl was 5.5%, for those with 1HrPG ≥143-<155 mg/dl, 5.6% and for those with 1HrPG ≥155 mg/dl, 5.7%. NGT subjects with 1HrPG ≥143-<155 mg/dl and ≥155 mg/dl had significantly higher BMI, waist circumference, systolic and diastolic blood pressure, triglyceride, total cholesterol/high-density lipoprotein (HDL ratio, triglyceride/HDL ratio, leukocyte count, and gamma glutamyl aminotransferase (P < 0.05 compared to subjects with 1HrPG <143 mg/dl. The odds ratio for MS for subjects with 1HrPG ≥143 mg/dl was 1.84 times higher compared to subjects with 1HrPG <143 mg/dl taken as the reference. Conclusion: NGT subjects with elevated 1HrPG values have a worse metabolic profile than those with normal 1HrPG during an OGTT.

  11. Astrocyte oxidative metabolism and metabolite trafficking after fluid percussion brain injury in adult rats.

    Science.gov (United States)

    Bartnik-Olson, Brenda L; Oyoyo, Udochukwu; Hovda, David A; Sutton, Richard L

    2010-12-01

    Despite various lines of evidence pointing to the compartmentation of metabolism within the brain, few studies have reported the effect of a traumatic brain injury (TBI) on neuronal and astrocyte compartments and/or metabolic trafficking between these cells. In this study we used ex vivo ¹³C NMR spectroscopy following an infusion of [1-¹³C] glucose and [1,2-¹³C₂] acetate to study oxidative metabolism in neurons and astrocytes of sham-operated and fluid percussion brain injured (FPI) rats at 1, 5, and 14 days post-surgery. FPI resulted in a decrease in the ¹³C glucose enrichment of glutamate in neurons in the injured hemisphere at day 1. In contrast, enrichment of glutamine in astrocytes from acetate was not significantly decreased at day 1. At day 5 the ¹³C enrichment of glutamate and glutamine from glucose in the injured hemisphere of FPI rats did not differ from sham levels, but glutamine derived from acetate metabolism in astrocytes was significantly increased. The ¹³C glucose enrichment of the C3 position of glutamate (C3) in neurons was significantly decreased ipsilateral to FPI at day 14, whereas the enrichment of glutamine in astrocytes had returned to sham levels at this time point. These findings indicate that the oxidative metabolism of glucose is reduced to a greater extent in neurons compared to astrocytes following a FPI. The increased utilization of acetate to synthesize glutamine, and the acetate enrichment of glutamate via the glutamate-glutamine cycle, suggests an integral protective role for astrocytes in maintaining metabolic function following TBI-induced impairments in glucose metabolism.

  12. Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

    Science.gov (United States)

    Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

    2015-03-01

    The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

  13. DLK1 Regulates Whole-Body Glucose Metabolism

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge

    2015-01-01

    due to impaired insulin signaling in OB and lowered Glu-OCN serum levels. Furthermore, Dlk1(-/-) mice treated with Glu-OC experienced significantly lower blood glucose levels than Glu-OCN-treated wild-type mice. The data suggest that Glu-OCN-controlled production of DLK1 by pancreatic β-cells acts...... metabolism. We show that Glu-OCN specifically stimulates Dlk1 expression by the pancreas. Conversely, Dlk1-deficient (Dlk1(-/-) ) mice exhibited increased circulating Glu-OCN levels and increased insulin sensitivity, whereas mice overexpressing Dlk1 in OB displayed reduced insulin secretion and sensitivity...

  14. Elevated glucose metabolism in the amygdala during an inhibitory avoidance task.

    Science.gov (United States)

    Sandusky, Leslie A; Flint, Robert W; McNay, Ewan C

    2013-05-15

    There is a long-standing debate as to whether the memory process of consolidation is neurochemically similar to or the same as the set of processes involved in retrieval and reconsolidation of that memory. In addition, although we have previously shown that initial memory processing in the hippocampus causes a drainage of hippocampal glucose because of increased local metabolic demand, it is unknown what metabolic changes occur elsewhere in the brain or during subsequent processing of a previously consolidated memory. Male Sprague Dawley rats (3 months old) were implanted with unilateral microdialysis cannulae and in vivo microdialysis of amygdala extracellular fluid (ECF) was performed during both (i) initial learning and (ii) retrieval 24 h later of an aversively motivated avoidance memory task. ECF samples were analyzed for glucose, lactate, pyruvate and glutamate. Results showed close similarity between increases in local glycolysis seen during both consolidation and retrieval, but also suggested that there may perhaps be a difference in amygdalar oxidative phosphorylation stimulated by the two processes. Hence, our data suggest that memory formation places similar metabolic demands across neural systems, and that consolidation may be metabolically different from retrieval. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Effect of glucose level on brain FDG-PET images

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Young; Lee, Yong Ki; Ahn, Sung Min [Dept. of Radiological Science, Gachon University, Seongnam (Korea, Republic of)

    2017-06-15

    In addition to tumors, normal tissues, such as the brain and myocardium can intake {sup 18}F-FDG, and the amount of {sup 18}F-FDG intake by normal tissues can be altered by the surrounding environment. Therefore, a process is necessary during which the contrasts of the tumor and normal tissues can be enhanced. Thus, this study examines the effects of glucose levels on FDG PET images of brain tissues, which features high glucose activity at all times, in small animals. Micro PET scan was performed on fourteen mice after injecting {sup 18}F-FDG. The images were compared in relation to fasting. The findings showed that the mean SUV value w as 0 .84 higher in fasted mice than in non-fasted mice. During observation, the images from non-fasted mice showed high accumulation in organs other than the brain with increased surrounding noise. In addition, compared to the non-fasted mice, the fasted mice showed higher early intake and curve increase. The findings of this study suggest that fasting is important in assessing brain functions in brain PET using {sup 18}F-FDG. Additional studies to investigate whether caffeine levels and other preprocessing items have an impact on the acquired images would contribute to reducing radiation exposure in patients.

  16. Effect of glucose level on brain FDG-PET images

    International Nuclear Information System (INIS)

    Kim, In Young; Lee, Yong Ki; Ahn, Sung Min

    2017-01-01

    In addition to tumors, normal tissues, such as the brain and myocardium can intake 18 F-FDG, and the amount of 18 F-FDG intake by normal tissues can be altered by the surrounding environment. Therefore, a process is necessary during which the contrasts of the tumor and normal tissues can be enhanced. Thus, this study examines the effects of glucose levels on FDG PET images of brain tissues, which features high glucose activity at all times, in small animals. Micro PET scan was performed on fourteen mice after injecting 18 F-FDG. The images were compared in relation to fasting. The findings showed that the mean SUV value w as 0 .84 higher in fasted mice than in non-fasted mice. During observation, the images from non-fasted mice showed high accumulation in organs other than the brain with increased surrounding noise. In addition, compared to the non-fasted mice, the fasted mice showed higher early intake and curve increase. The findings of this study suggest that fasting is important in assessing brain functions in brain PET using 18 F-FDG. Additional studies to investigate whether caffeine levels and other preprocessing items have an impact on the acquired images would contribute to reducing radiation exposure in patients

  17. Consumption of Alcopops During Brain Maturation Period: Higher Impact of Fructose Than Ethanol on Brain Metabolism

    Directory of Open Access Journals (Sweden)

    Dounia El Hamrani

    2018-05-01

    Full Text Available Alcopops are flavored alcoholic beverages sweetened by sodas, known to contain fructose. These drinks have the goal of democratizing alcohol among young consumers (12–17 years old and in the past few years have been considered as fashionable amongst teenagers. Adolescence, however, is a key period for brain maturation, occurring in the prefrontal cortex and limbic system until 21 years old. Therefore, this drinking behavior has become a public health concern. Despite the extensive literature concerning the respective impacts of either fructose or ethanol on brain, the effects following joint consumption of these substrates remains unknown. Our objective was to study the early brain modifications induced by a combined diet of high fructose (20% and moderate amount of alcohol in young rats by 13C Nuclear Magnetic Resonance (NMR spectroscopy. Wistar rats had isocaloric pair-fed diets containing fructose (HF, 20%, ethanol (Et, 0.5 g/day/kg or both substrates at the same time (HFEt. After 6 weeks of diet, the rats were infused with 13C-glucose and brain perchloric acid extracts were analyzed by NMR spectroscopy (1H and 13C. Surprisingly, the most important modifications of brain metabolism were observed under fructose diet. Alterations, observed after only 6 weeks of diet, show that the brain is vulnerable at the metabolic level to fructose consumption during late-adolescence throughout adulthood in rats. The main result was an increase in oxidative metabolism compared to glycolysis, which may impact lactate levels in the brain and may, at least partially, explain memory impairment in teenagers consuming alcopops.

  18. Effect of CoO nanoparticles on the carbohydrate metabolism of the brain of

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    Shamshad M. Shaikh

    2016-10-01

    Full Text Available The effect of CoO nanoparticles (NPs on the brain of mice administered through gastrointestinal tract for a period of 30 days was studied. AAS analysis revealed that NPs administered orally were retained by cerebellum, cerebral cortex, medulla oblongata and olfactory bulb. This retention of nanoparticles by the brain promoted a significant increase in glucose, pyruvate, lactate and glycogen levels along with the concomitant increase in hexokinase, glucose 6 phosphatase, and lactate dehydrogense activities. However, a decrease in glucose 6 phosphate dehydrogenase activity was observed in the brain regions indicating a deterioration of the pentose phosphate pathway. Thus, the present study suggests that the CoO NPs affect the carbohydrate metabolism of the brain.

  19. Regulation of Lipid and Glucose Metabolism by Phosphatidylcholine Transfer Protein

    Science.gov (United States)

    Kang, Hye Won; Wei, Jie; Cohen, David E.

    2010-01-01

    Phosphatidylcholine transfer protein (PC-TP, a.k.a. StARD2) binds phosphatidylcholines and catalyzes their intermembrane transfer and exchange in vitro. The structure of PC-TP comprises a hydrophobic pocket and a well-defined head-group binding site, and its gene expression is regulated by peroxisome proliferator activated receptor α. Recent studies have revealed key regulatory roles for PC-TP in lipid and glucose metabolism. Notably, Pctp−/− mice are sensitized to insulin action and exhibit more efficient brown fat-mediated thermogenesis. PC-TP appears to limit access of fatty acids to mitochondria by stimulating the activity of thioesterase superfamily member 2, a newly characterized long-chain fatty acyl-CoA thioesterase. Because PC-TP discriminates among phosphatidylcholines within lipid bilayers, it may function as a sensor that links metabolic regulation to membrane composition. PMID:20338778

  20. Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

    Science.gov (United States)

    Besson, Marie Thérèse; Alegría, Karin; Garrido-Gerter, Pamela; Barros, Luis Felipe; Liévens, Jean-Charles

    2015-01-01

    Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to mediate the hGluT3

  1. Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model.

    Directory of Open Access Journals (Sweden)

    Marie Thérèse Besson

    Full Text Available Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93. We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD, the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to

  2. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

    Science.gov (United States)

    Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

    2014-04-01

    Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are

  3. The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

    Science.gov (United States)

    Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

    2015-01-01

    Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

  4. Carbon balance studies of glucose metabolism in rat cerebral cortical synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, U; Brand, K

    1982-07-01

    Synaptosomes were isolated from rat cerebral cortex and incubated with (U-/sup 14/C)-, (1-/sup 14/C)- or (6-/sup 14/C)glucose. Glucose utilization and the metabolic partitioning of glucose carbon in products were determined by isotopic methods. From the data obtained a carbon balance was constructed, showing lactate to be the main product of glucose metabolism, followed by CO/sup 2/, amino acids and pyruvate. Measuring the release of /sup 14/CO/sup 2/ from glucose labelled in three different positions allowed the construction of a flow diagram of glucose carbon atoms in synaptosomes, which provides information about the contribution of the various pathways of glucose metabolism. Some 2% of glucose utilized was calculated to be degraded via the pentose phosphate pathway. Addition of chlorpromazine, imipramine or haloperidol at concentrations of 10(-5) M reduced glucose utilisation by 30% without changing the distribution pattern of radioactivity in the various products.

  5. The effect of insulin resistance on amygdale glucose metabolism alterations in experimental Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ya. V. Gorina

    2017-01-01

    Full Text Available Purpose. Glucose metabolism is tightly regulated in the brain. Aberrant glucose metabolism is an important feature of neurodegenerative diseases, as inAlzheimer’s disease. The transport of glucose to the cell membrane is realized through the activity of insulin-regulated aminopeptidase (IRAP which controls transfer of glucose transporter to the plasma membrane. IRAP is considered as one of the key markers of insulin resistance in Alzheimer’s disease. However, the question of the mechanism of the action of the IRAP remains open. The aim of the study was to study the effect of IRAP expression on cells of the neuronal and glial lineage, glucose transporter (GLUT4 expression in the brain amygdala on emotional memory in animals with experimental Alzheimer’s disease.Materials and methods. The study was performed with two experimental models of Alzheimer’s disease in mice. The experimental group was mice of the CD1 line, males aged 4 months (Alzheimer’s disease model with the intra-hippocampal administration of beta-amyloid 1-42 (1 µl bilaterally in the CA1 area. The control group was mice of the CD1 line, males aged 4 months (sham-operated animals with the intrahippocampal administration of Phosphate buffered salin (1 µl bilaterally in the CA1. The genetic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon, PSEN1*M146L*L286V 6799Vas, males aged 4 months. The control group consisted of C57BL/6xSJL mice, males aged 4 months. Evaluation of emotional memory was carried out using “Fear conditioning” protocol. Expression of molecule-markers of insulin-resistance in the amygdala was studied by immunohistochemistry followed by confocal microscopy.Results. Aberrant associative learning and emotional memory was revealed in animals with an experimental model of Alzheimer’s disease. A decrease (p ≤ 0,05 of IRAP expression on cells of neuronal and glial nature, associated with GLUT4 down-regulation was detected in amygdala of

  6. Regional cerebral glucose metabolic changes in oculopalatal myoclonus: implication for neural pathways, underlying the disorder

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Moon, So Young; Kim, Ji Soo; Kim, Sang Eun

    2004-01-01

    Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat. When associated with eye movements, it is called oculopalatal myoclonus (OPM). Ordinary PM is characterized by hypertrophic olivary degeneration, a trans-synaptic degeneration following loss of neuronal input to the inferior olivary nucleus due to an interruption of the Guillain-Mollaret triangle usually by a hemorrhage. However, the neural pathways underlying the disorder are uncertain. In an attempt to understand the pathologic neural pathways, we examined the metabolic correlates of this tremulous condition. Brain FDG PET scans were acquired in 8 patients with OPM (age, 49.9±4.6 y: all males: 7 with pontine hemorrhage, 1 with diffuse brainstem infarction) and age-matched 50 healthy males (age, 50.7± 9.0) and the regional glucose metabolism compared using SPM99. For group analysis, the hemispheres containing lesions were assigned to the right side of the brain. Patients with OPM had significant hypometabolism in the ipsilateral (to the lesion) brainstem and superior temporal and parahippocampal gyri (P < 0.05 corrected, k = 100). By contrast, there was significant hypermetabolism in the contralateral middle and inferior temporal gyri, thalamus, middle frontal gyrus and precuneus (P < 0.05 corrected, k=l00). Our data demonstrate the distinct metabolic changes between several ipsilateral and contralateral brain regions (hypometabolism vs. hypermetabolism) in patients with OPM. This may provide clues for understanding the neural pathways underlying the disorder

  7. Regional cerebral glucose metabolic changes in oculopalatal myoclonus: implication for neural pathways, underlying the disorder

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Moon, So Young; Kim, Ji Soo; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat. When associated with eye movements, it is called oculopalatal myoclonus (OPM). Ordinary PM is characterized by hypertrophic olivary degeneration, a trans-synaptic degeneration following loss of neuronal input to the inferior olivary nucleus due to an interruption of the Guillain-Mollaret triangle usually by a hemorrhage. However, the neural pathways underlying the disorder are uncertain. In an attempt to understand the pathologic neural pathways, we examined the metabolic correlates of this tremulous condition. Brain FDG PET scans were acquired in 8 patients with OPM (age, 49.9{+-}4.6 y: all males: 7 with pontine hemorrhage, 1 with diffuse brainstem infarction) and age-matched 50 healthy males (age, 50.7{+-} 9.0) and the regional glucose metabolism compared using SPM99. For group analysis, the hemispheres containing lesions were assigned to the right side of the brain. Patients with OPM had significant hypometabolism in the ipsilateral (to the lesion) brainstem and superior temporal and parahippocampal gyri (P < 0.05 corrected, k = 100). By contrast, there was significant hypermetabolism in the contralateral middle and inferior temporal gyri, thalamus, middle frontal gyrus and precuneus (P < 0.05 corrected, k=l00). Our data demonstrate the distinct metabolic changes between several ipsilateral and contralateral brain regions (hypometabolism vs. hypermetabolism) in patients with OPM. This may provide clues for understanding the neural pathways underlying the disorder.

  8. Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Jeffrey Thomas Cole

    2012-04-01

    Full Text Available Brain cells expend large amounts of energy sequestering calcium (Ca2+, while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P, a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA. Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, 45Ca2+ accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi coupled with Ca2+ accumulation was quantified. Addition of G6P significantly and decreased Ca2+ accumulation in a dose-dependent fashion (1-10 mM. The reduction in Ca2+ accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca2+ accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca2+ uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca2+ dystasis caused by altered G6P regulation of SERCA activity

  9. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

    Directory of Open Access Journals (Sweden)

    Laura ePaixão

    2015-10-01

    Full Text Available Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal, N-acetylglucosamine (GlcNAc and mannose (Man affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome. In central carbon metabolism (most represented category, Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

  10. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

    Science.gov (United States)

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

  11. Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.

    Science.gov (United States)

    Linder, Katarzyna; Schleger, Franziska; Ketterer, Caroline; Fritsche, Louise; Kiefer-Schmidt, Isabelle; Hennige, Anita; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas

    2014-06-01

    Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03). Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.

  12. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

    Science.gov (United States)

    Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

    2016-10-01

    Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

  14. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    KAUST Repository

    Baud, Maxime O.

    2016-05-03

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.

  15. Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

    Science.gov (United States)

    Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

    2017-08-01

    Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro

  16. Energetics of glucose metabolism: a phenomenological approach to metabolic network modeling.

    Science.gov (United States)

    Diederichs, Frank

    2010-08-12

    A new formalism to describe metabolic fluxes as well as membrane transport processes was developed. The new flux equations are comparable to other phenomenological laws. Michaelis-Menten like expressions, as well as flux equations of nonequilibrium thermodynamics, can be regarded as special cases of these new equations. For metabolic network modeling, variable conductances and driving forces are required to enable pathway control and to allow a rapid response to perturbations. When applied to oxidative phosphorylation, results of simulations show that whole oxidative phosphorylation cannot be described as a two-flux-system according to nonequilibrium thermodynamics, although all coupled reactions per se fulfill the equations of this theory. Simulations show that activation of ATP-coupled load reactions plus glucose oxidation is brought about by an increase of only two different conductances: a [Ca(2+)] dependent increase of cytosolic load conductances, and an increase of phosphofructokinase conductance by [AMP], which in turn becomes increased through [ADP] generation by those load reactions. In ventricular myocytes, this feedback mechanism is sufficient to increase cellular power output and O(2) consumption several fold, without any appreciable impairment of energetic parameters. Glucose oxidation proceeds near maximal power output, since transformed input and output conductances are nearly equal, yielding an efficiency of about 0.5. This conductance matching is fulfilled also by glucose oxidation of β-cells. But, as a price for the metabolic mechanism of glucose recognition, β-cells have only a limited capability to increase their power output.

  17. Predicting glucose intolerance with normal fasting plasma glucose by the components of the metabolic syndrome

    International Nuclear Information System (INIS)

    Pei, D.; Lin, J.; Kuo, S.; Wu, D.; Li, J.; Hsieh, C.; Wu, C.; Hung, Y.; Kuo, K.

    2007-01-01

    Surprisingly it is estimated that about half of type 2 diabetics remain undetected. The possible causes may be partly attributable to people with normal fasting plasma glucose (FPG) but abnormal postprandial hyperglycemia. We attempted to develop an effective predictive model by using the metabolic syndrome (MeS) components as parameters to identify such persons. All participants received a standard 75 gm oral glucose tolerance test which showed that 106 had normal glucose tolerance, 61 had impaired glucose tolerance and 6 had diabetes on isolated postchallenge hyperglycemia. We tested five models which included various MeS components. Model 0: FPG; Model 1 (Clinical history model): family history (FH), FPG, age and sex; Model 2 (MeS model): Model 1 plus triglycerides, high-density lipoprotein cholesterol, body mass index, systolic blood pressure and diastolic blood pressure; Model 3: Model 2 plus fasting plasma insulin (FPI); Model 4: Model 3 plus homeostasis model assessment of insulin resistance. A receiver-operating characteristic (ROC) curve was used to determine the predictive discrimination of these models. The area under the ROC curve of the Model 0 was significantly larger than the area under the diagonal reference line. All the other 4 models had a larger area under the ROC curve than Model 0. Considering the simplicity and lower cost of Model 2, it would be the best model to use. Nevertheless, Model 3 had the largest area under the ROC curve. We demonstrated that Model 2 and 3 have a significantly better predictive discrimination to identify persons with normal FPG at high risk for glucose intolerance. (author)

  18. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

    Science.gov (United States)

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2016-01-01

    Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

  19. Investigation of (/sup 18/F)2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-12-01

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man.

  20. Investigation of [18F]2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    International Nuclear Information System (INIS)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-01-01

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man

  1. Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Murrin L Charles

    2011-03-01

    Full Text Available Abstract Background Methamphetamine (METH, an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB to date. Results In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM increased the expression of glucose transporter protein-1 (GLUT1 in primary human brain endothelial cell (hBEC, main component of BBB without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function. Conclusion Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

  2. Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") administration in awake rats

    DEFF Research Database (Denmark)

    Gramsbergen, Jan Bert; Cumming, Paul

    2007-01-01

     The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose...... was monitored by telemetry. A single dose of MDMA (2-10-20 mg/kg i.v.) evoked a transient increase of interstitial glucose concentrations in striatum (139-223%) with rapid onset and of less than 2h duration, a concomitant but more prolonged lactate increase (>187%) at the highest MDMA dose and no significant...... depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1...

  3. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults.

    Science.gov (United States)

    Witte, A Veronica; Kerti, Lucia; Margulies, Daniel S; Flöel, Agnes

    2014-06-04

    Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanisms underlying this effect. Twenty-three healthy overweight older individuals that successfully completed 26 weeks of resveratrol intake (200 mg/d) were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50-75 years). Before and after the intervention/control period, subjects underwent memory tasks and neuroimaging to assess volume, microstructure, and functional connectivity (FC) of the hippocampus, a key region implicated in memory functions. In addition, anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors, and vascular parameters were assayed. We observed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038). In addition, resveratrol led to significant increases in hippocampal FC, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p memory performance in association with improved glucose metabolism and increased hippocampal FC in older adults. Our findings offer the basis for novel strategies to maintain brain health during aging. Copyright © 2014 the authors 0270-6474/14/347862-09$15.00/0.

  4. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    Science.gov (United States)

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge. © 2014 The Authors. The Journal of Physiology © 2014

  5. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    International Nuclear Information System (INIS)

    Meguro, K.; Doi, C.; Yamaguchi, T.; Sasaki, H.; Matsui, H.; Yamada, K.; Kinomura, S.; Tohoku Univ.; Itoh, M.

    1991-01-01

    Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the 18 -F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolsim in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. (orig.)

  6. Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Fellgiebel, Andreas; Siessmeier, Thomas; Winterer, Georg; Lüddens, Hartmut; Mann, Klaus; Schmidt, Lutz G; Bartenstein, Peter

    2004-01-01

    To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff syndrome. Two cases of alcoholic Wernicke-Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.

  7. Kisspeptin and Metabolism: The Brain and Beyond

    Directory of Open Access Journals (Sweden)

    Monika Dudek

    2018-04-01

    Full Text Available Apart from the well-established role of kisspeptin (Kp in the regulation of reproductive functions, recent data described its action in the control of metabolism. Of particular interest for the review is the population of Kp neurons localized in the arcuate nucleus (ARC of the hypothalamus, the site of the brain where reproductive and metabolic cross talk occurs. However, within the hypothalamus Kp does not work alone, but rather interacts with other neuropeptides, e.g., neurokinin B, dynorphin A, proopiomelanocortin, the cocaine- and amphetamine-regulated transcript, agouti-related peptide, and neuropeptide Y. Beyond the brain, Kp is expressed in peripheral tissues involved in metabolic functions. In this review, we will mainly focus on the local action of this peptide in peripheral organs such as the pancreas, liver, and the adipose tissue. We will concentrate on dysregulation of the Kp system in cases of metabolic imbalance, e.g., obesity and diabetes. Importantly, these patients besides metabolic health problems often suffer from disruptions of the reproductive system, manifested by abnormalities in menstrual cycles, premature child birth, miscarriages in women, decreased testosterone levels and spermatogenesis in men, hypogonadism, and infertility. We will review the evidence from animal models and clinical data indicating that Kp could serve as a promising agent with clinical applications in regulation of reproductive problems in individuals with obesity and diabetes. Finally, emerging data indicate a role of Kp in regulation of insulin secretion, potentially leading to development of further therapeutic uses of this peptide to treat metabolic problems in patients with these lifestyle diseases.

  8. Kisspeptin and Metabolism: The Brain and Beyond.

    Science.gov (United States)

    Dudek, Monika; Ziarniak, Kamil; Sliwowska, Joanna H

    2018-01-01

    Apart from the well-established role of kisspeptin (Kp) in the regulation of reproductive functions, recent data described its action in the control of metabolism. Of particular interest for the review is the population of Kp neurons localized in the arcuate nucleus (ARC) of the hypothalamus, the site of the brain where reproductive and metabolic cross talk occurs. However, within the hypothalamus Kp does not work alone, but rather interacts with other neuropeptides, e.g., neurokinin B, dynorphin A, proopiomelanocortin, the cocaine- and amphetamine-regulated transcript, agouti-related peptide, and neuropeptide Y. Beyond the brain, Kp is expressed in peripheral tissues involved in metabolic functions. In this review, we will mainly focus on the local action of this peptide in peripheral organs such as the pancreas, liver, and the adipose tissue. We will concentrate on dysregulation of the Kp system in cases of metabolic imbalance, e.g., obesity and diabetes. Importantly, these patients besides metabolic health problems often suffer from disruptions of the reproductive system, manifested by abnormalities in menstrual cycles, premature child birth, miscarriages in women, decreased testosterone levels and spermatogenesis in men, hypogonadism, and infertility. We will review the evidence from animal models and clinical data indicating that Kp could serve as a promising agent with clinical applications in regulation of reproductive problems in individuals with obesity and diabetes. Finally, emerging data indicate a role of Kp in regulation of insulin secretion, potentially leading to development of further therapeutic uses of this peptide to treat metabolic problems in patients with these lifestyle diseases.

  9. GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, M.; Brock, B.; Egefjord, L.

    2017-01-01

    transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P cerebral cortex as a whole compared...... and degeneration. Hypothesis: The incretin hormone GLP-1 prevents the decline of the cerebral metabolic rate of glucose that signifies cognitive impairment, synaptic dysfunction, and disease evolution in AD, and GLP-1 may directly activate GLUT1 transport in brain capillary endothelium. For this reason, we here...

  10. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD.

  11. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    International Nuclear Information System (INIS)

    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E.

    2002-01-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD

  12. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain

    Science.gov (United States)

    Marin-Valencia, Isaac; Good, Levi B; Ma, Qian; Malloy, Craig R; Pascual, Juan M

    2013-01-01

    It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-13C3]heptanoate was examined in the normal mouse brain and in G1D by 13C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in 13C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and 13C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism. PMID:23072752

  13. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

    International Nuclear Information System (INIS)

    Kwak, Young Bin; Cho, Sang Soo; Lee, Sung Ha; Chey, Jean Yung; Kim, Sang Eun

    2004-01-01

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.1±4.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.69±0.09 μ g/dL), while 14 (mean age, 67.2±4.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.27±0.03 μ g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted

  14. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Young Bin; Cho, Sang Soo; Lee, Sung Ha; Chey, Jean Yung; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2004-07-01

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.1{+-}4.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.69{+-}0.09 {mu} g/dL), while 14 (mean age, 67.2{+-}4.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.27{+-}0.03 {mu} g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted.

  15. Investigations on the effects of ''Ecstasy'' on cerebral glucose metabolism: an 18-FDG PET study

    International Nuclear Information System (INIS)

    Schreckenberger, M.; Sabri, O.; Arning, C.; Tuttass, T.; Schulz, G.; Kaiser, H.J.; Wagenknecht, G.; Buell, U.; Gouzoulis-Mayfrank, E.; Sass, H.

    1998-01-01

    Purpose: The aim of the present study was to determine the acute effects of the 'Ecstasy' analogue MDE (3,4-methylendioxyethamphetamine) on the cerebral glucose metabolism (rMRGlu) of healthy volunteers. Method: In a randomised double-blind trial, 16 healthy volunteers without a history of drug abuse were examined with 18-FDG PET 110-120 minutes after oral administration of 2 mg/kg MDE (n=8) or placebo (n=8). Beginning two minutes prior to radiotracer injection, a constant cognitive stimulation was maintained for 32 minutes using a word repetition paradigm in order to ensure constant and comparable mental conditions during cerebral 18-FDG uptake. Individual brain anatomy was represented using T1-weighted 3D flash MRI, followed by manual regionalisation into 108 regions-of-interest and PET/MRI overlay. Absolute quantification of rMRGlu and comparison of glucose metabolism under MDE versus placebo were performed using Mann-Whitney U-test. Results: Absolute global MRGlu was not significantly changed under MDE versus placebo (MDE: 41,8±11,1 μmol/min/100 g, placebo: 50,1±18,1 μmol/min/100 g, p=0,298). The normalised regional metabolic data showed a significantly decreased rMRGlu in the bilateral frontal cortex: Left frontal posterior (-7.1%, p [de

  16. Impaired insulin action in the human brain: causes and metabolic consequences.

    Science.gov (United States)

    Heni, Martin; Kullmann, Stephanie; Preissl, Hubert; Fritsche, Andreas; Häring, Hans-Ulrich

    2015-12-01

    Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.

  17. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

    Science.gov (United States)

    Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

    2002-03-01

    Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

  18. Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers

    OpenAIRE

    Louis, Mariam; Punjabi, Naresh M.

    2009-01-01

    Accumulating evidence suggests that obstructive sleep apnea is associated with alterations in glucose metabolism. Although the pathophysiology of metabolic dysfunction in obstructive sleep apnea is not well understood, studies of murine models indicate that intermittent hypoxemia has an important contribution. However, corroborating data on the metabolic effects of intermittent hypoxia on glucose metabolism in humans are not available. Thus the primary aim of this study was to characterize th...

  19. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

    Directory of Open Access Journals (Sweden)

    Seyfried B

    2009-09-01

    Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  20. Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

    Science.gov (United States)

    Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

    2015-08-01

    Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  1. Physical Activity Dimensions Associated with Impaired Glucose Metabolism

    DEFF Research Database (Denmark)

    Amadid, Hanan; Johansen, Nanna B.; Bjerregaard, Anne-Louise

    2017-01-01

    Purpose Physical activity (PA) is important in the prevention of Type 2 diabetes, yet little is known about the role of specific dimensions of PA, including sedentary time in subgroups at risk for impaired glucose metabolism (IGM). We applied a data-driven decision tool to identify dimensions of PA...... identified subgroups in which different activity dimensions were associated with IGM. Methodology and results from this study may suggest a preliminary step toward the goal of tailoring and targeting PA interventions aimed at Type 2 diabetes prevention....... associated with IGM across age, sex, and body mass index (BMI) groups. Methods This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8) yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured by an individually calibrated combined accelerometer and heart rate...

  2. The estrogen hypothesis of schizophrenia implicates glucose metabolism

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D

    2008-01-01

    expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task....... We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks...... implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia...

  3. Investigation of 18F-2-deoxyglucose for the measure of myocardial glucose metabolism

    International Nuclear Information System (INIS)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.R.; Kuhl, D.E.

    1977-01-01

    18 F labeled 2-deoxyglucose ( 18 FDG) was studied as a glucose analog. Myocardial uptake and retention, blood clearance, species (dog, monkey, man) dependence and effect of diet on uptake were investigated. Normal myocardial uptake of 18 FDG was 3 to 4% in dog and monkey and 1 to 4% of injected dose in man compared to brain uptake of 2% in dog, 5 to 6% in monkey and 4 to 8% in man. The metabolic rate (MR) for glucose in non-fasting (glycolytic state) was 2.8 times greater than in fasting (ketogenic state). Human subjects showed higher myocardial uptake after a normal meal than after meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t 1 / 2 of 0.2 to 0.3 min followed by a t 1 / 2 of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had a t 1 / 2 of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. High image contrast ratios between heart and blood (dog 3.5/1; man 14/1), heart and lung (dog 9/1; man 20/1), heart and liver (dog 15/1; man 10/1) were found with the ECAT positron tomograph. 18 FDG was found to be rapidly taken up by the myocardium without any significant tissue clearance over a 4 hour period. 18 FDG is transported, phosphorylated to 18 FDG-6-PO 4 and trapped in myocardial cells in the same manner as has been found for brain and exhibits excellent imaging properties. Determination of glucose and FFA MR in vivo with ECT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man

  4. Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

    International Nuclear Information System (INIS)

    Beck, T.; Krieglstein, J.

    1987-01-01

    The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O 2 . Hypoxia affected a marked hypotension, hypocapnia and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40-70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU and were detectable in cortical gray matter. Color-coded [ 14 C]2-deoxy-D-glucose autoradiograms of rat brain are shown. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggests a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur

  5. Comparison of cerebral metabolism of glucose in normal human and cancer patients

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: Objective: To determine whether the cerebral metabolism in various regions of the normal human brain differs from those of cancer patients in aging by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples so called 'normal group' (ranging 21 to 88; mean age+/-SD: 50+/-14) and 290 cancer patients called 'cancer group' (ranging 21 to 85; mean age+/-SD: 54+/-14) who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They were selected with: (i) absence of clear focal brain lesions (epilepsy, cerebrovascular diseases etc.); (ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes; (iii) absence of psychiatric disorders and abuse of drugs and alcohol;( iiii) cancer patients were diagnosed definitely of variable cancers except brain cancer or brain metastasis. Both groups were sub grouped into six with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose are matched. All 12 subgroups were compared to the subgroup of normal 31-40 years old called 'control subgroup' (84 samples; mean age+/-SD: 37.15+/- 2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later; their brains were scanned for 10 minutes. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2). The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three dimensional localized by MNI Space utility (MSU) software. Results:1.With increasing of age interval, similar hypometabolic brain areas are detected in both 'normal group' and 'cancer group', they are mainly in the cortical structures such as bilateral prefrontal cortex (BA9), superior temporal gyrus (BA22), parietal cortex (inferior parietal lobule and precuneus(BA40), insula (BA13

  6. Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2005-04-01

    Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

  7. Impaired Glucose Metabolism Despite Decreased Insulin Resistance After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Manfred Hecking

    2012-06-01

    Full Text Available The pathophysiology underlying new-onset diabetes after transplantation (NODAT is unresolved. We obtained demographics and laboratory data from all 1064 renal transplant recipients followed at our outpatient clinic in 2009/2010, randomly assigned 307 patients without previously diagnosed diabetes to a routine 2-hour oral glucose tolerance test (OGTT, and compared the metabolic results to a large, unrelated cross-sectional cohort of non-transplanted subjects. Among renal transplant recipients, 11% had a history of NODAT, and 12% had type 1 and type 2 diabetes. 42% of all OGTTs were abnormal (9% diabetic, predominantly in older patients who received tacrolimus. Compared to non-transplanted subjects, basal glucose was lower and HbA1c higher in renal transplant patients. Compared to non-transplanted subjects, insulin secretion was inferior, and insulin sensitivity improved at ≥6 months, as well as 3 months post-transplantation:(The Figure shows linear spline interpolation; all p for overall difference between non-Tx and Tx patients <0.02, using likelihood ratio testing. Our results indicate that impaired insulin secretion is the predominant problem after renal transplantation, suggesting benefit for therapeutic regimens that preserve beta cell function after renal transplantation. The mechanism of increased insulin sensitivity might be pathophysiologically similar to pancreatogenic diabetes.fx1

  8. A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Quistorff, Bjørn; Danielsen, Else R

    2003-01-01

    During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differe......During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio......-venous differences (AV) for O(2), glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy.......0 to 0.9 +/- 0.1 mM (P ratio from 6.0 +/- 0.3 to 2.8 +/- 0.2 (P

  9. Analysis of metabolism of 6FDG: a PET glucose transport tracer

    Energy Technology Data Exchange (ETDEWEB)

    Muzic, Raymond F., E-mail: raymond.muzic@case.edu [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Chandramouli, Visvanathan [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Huang, Hsuan-Ming [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Wu Chunying; Wang Yanming [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Ismail-Beigi, Faramarz [Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2011-07-15

    Introduction: We are developing {sup 18}F-labeled 6-fluoro-6-deoxy-D-glucose ([{sup 18}F]6FDG) as a tracer of glucose transport. As part of this process it is important to characterize and quantify putative metabolites. In contrast to the ubiquitous positron emission tomography (PET) tracer {sup 18}F-labeled 2-fluoro-2-deoxy-D-glucose ([{sup 18}F]2FDG) which is phosphorylated and trapped intracellularly, the substitution of fluorine for a hydroxyl group at carbon-6 in [{sup 18}F]6FDG should prevent its phosphorylation. Consequently, [{sup 18}F]6FDG has the potential to trace the transport step of glucose metabolism without the confounding effects of phosphorylation and subsequent steps of metabolism. Herein the focus is to determine whether, and the degree to which, [{sup 18}F]6FDG remains unchanged following intravenous injection. Methods: Biodistribution studies were performed using 6FDG labeled with {sup 18}F or with the longer-lived radionuclides {sup 3}H and {sup 14}C. Tissues were harvested at 1, 6, and 24 h following intravenous administration and radioactivity was extracted from the tissues and analyzed using a combination of ion exchange columns, high-performance liquid chromatography, and chemical reactivity. Results: At the 1 h time-point, the vast majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood was identified as 6FDG. At the 6-h and 24-h time points, there was evidence of a minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D-sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. Conclusion: On the time scale typical of PET imaging studies radioactive metabolites of [{sup 18}F]6FDG are negligible.

  10. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-02-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled (/sup 14/C)glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-(1,2-/sup 14/C)choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis.

  11. Effects of CDP-choline on neurologic deficits and cerebral glucose metabolism in a rat model of cerebral ischemia

    International Nuclear Information System (INIS)

    Kakihana, M.; Fukuda, N.; Suno, M.; Nagaoka, A.

    1988-01-01

    The effects of cytidine 5'-diphosphocholine (CDP-choline) on neurologic deficits and cerebral glucose metabolism were studied in a rat model of transient cerebral ischemia. Cerebral ischemia was induced by occluding both common carotid arteries for 20 or 30 minutes 24 hours after the vertebral arteries were permanently occluded by electrocautery. CDP-choline was administered intraperitoneally twice daily for 4 days after reestablishing carotid blood flow. CDP-choline at two dosages (50 and 250 mg/kg) shortened the time required for recovery of spontaneous motor activity in a dose-related manner; recovery time was measured early after reperfusion. Neurologic signs were observed for 10 days. High-dose CDP-choline improved neurologic signs in the rats within 20-30 minutes of ischemia. When cerebral glucose metabolism was assessed on Day 4, increases in the levels of glucose and pyruvate were accompanied by decreases in the synthesis of labeled acetylcholine from uniformly labeled [ 14 C]glucose measured in the cerebral cortex of rats with 30 minutes of ischemia. High-dose CDP-choline also attenuated changes in these variables. CDP-[1,2- 14 C]choline injected intravenously 10 minutes after reperfusion was used for membrane lipid biosynthesis. These results indicate that CDP-choline has beneficial effects on brain dysfunction induced by cerebral ischemia, which may be due in part to the restorative effects of CDP-choline on disturbed cerebral glucose metabolism, probably by stimulating phospholipid biosynthesis

  12. Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

    Science.gov (United States)

    Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki; Cook, Michelle; Law, Mona J; Kaufman, Elaine; Sokoloff, Louis

    2003-04-15

    Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

  13. Effect of supplemental protein source during the winter on pre- and postpartum glucose metabolism

    Science.gov (United States)

    Circulating serum glucose concentrations as well as glucose utilization have been shown to be affected by forage quality. Supplemental protein provided to grazing range cows while consuming low quality forage may improve glucose metabolism. The objective of our study was to determine the effects of ...

  14. Energy metabolism and memory processing: role of glucose transport and glycogen in responses to adrenoceptor activation in the chicken.

    Science.gov (United States)

    Hutchinson, Dana S; Summers, Roger J; Gibbs, Marie E

    2008-06-15

    From experiments using a discriminated bead task in young chicks, we have defined when and where adrenoceptors (ARs) are involved in memory modulation. All three ARs subtypes (alpha(1)-, alpha(2)- and beta-ARs) are found in the chick brain and in regions associated with memory. Glucose and glycogen are important in the role of memory consolidation in the chick since increasing glucose levels improves memory consolidation while inhibiting glucose transporters (GLUTs) or glycogen breakdown inhibits memory consolidation. The selective beta(3)-AR agonist CL316243 enhances memory consolidation by a glucose-dependent mechanism and the administration of the non-metabolized glucose analogue 2-deoxyglucose reduces the ability of CL316243 to enhance memory. Agents that reduce glucose uptake by GLUTs and its incorporation into the glycolytic pathway also reduce the effectiveness of CL316243, but do not alter the dose-response relationship to the beta(2)-AR agonist zinterol. However, beta(2)-ARs do have a role in memory related to glycogen breakdown and inhibition of glycogenolysis reduces the ability of zinterol to enhance memory. Both beta(2)- and beta(3)-ARs are found on astrocytes from chick forebrain, and the actions of beta(3)-ARs on glucose uptake, and beta(2)-ARs on the breakdown of glycogen is consistent with an effect on astrocytic metabolism at the time of memory consolidation 30 min after training. We have shown that both beta(2)- and beta(3)-ARs can increase glucose uptake in chick astrocytes but do so by different mechanisms. This review will focus on the role of ARs on memory consolidation and specifically the role of energy metabolism on AR modulation of memory.

  15. Impaired glucose metabolism in HIV-infected pregnant women: a retrospective analysis.

    LENUS (Irish Health Repository)

    Moore, Rebecca

    2015-05-20

    Metabolic complications including diabetes mellitus have been increasingly recognised in HIV-infected individuals since the introduction of antiretroviral therapy, particularly protease inhibitors (PIs). Pregnancy is also a risk factor for impaired glucose metabolism, and previous studies have given conflicting results regarding the contribution of PIs to impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) in pregnant HIV-infected women.

  16. The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1992-12-01

    The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The [sup 18]F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal [sup 18]F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The [sup 18]F-Dopa uptake in the striatum increased and th