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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. 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...... different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging....... 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...

  3. 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.)

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

    OpenAIRE

    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 enc...

  5. 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

    2016-01-01

    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. PMID:26964832

  6. 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 exa

  7. Weight Loss After Bariatric Surgery Reverses Insulin-Induced Increases in Brain Glucose Metabolism of the Morbidly Obese

    OpenAIRE

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

    2013-01-01

    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 dif...

  8. Relationship of impaired brain glucose metabolism to learning deficit in the senescence-accelerated mouse.

    Science.gov (United States)

    Ohta, H; Nishikawa, H; Hirai, K; Kato, K; Miyamoto, M

    1996-10-11

    The relationship between brain glucose metabolism and learning deficit was examined in the senescence-accelerated-prone mouse (SAMP) 8, which has been proven to be a useful murine model of age-related behavioral disorders. SAMP8, 7 months old, exhibited marked learning impairment in the passive avoidance task, as compared with the control strain, senescence-accelerated-resistant mice (SAMR) 1. SAMP8 also exhibited a reduction in brain glucose metabolism, as indicated by a reduction in [14C]2-deoxyglucose accumulation in the brain following the intravenous injection impaired glucose metabolism correlated significantly with the learning impairment in all brain regions in SAMR1 and SAMP8. In the SAMP8, a significant correlation was observed in the posterior half of the cerebral cortex. These results suggest that the SAMP8 strain is a useful model of not only age-related behavioral disorders, but also glucose hypometabolism observed in aging and dementias. PMID:8905734

  9. 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.

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

    International Nuclear Information System (INIS)

    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

  11. Acute Alcohol Intoxication Decreases Glucose Metabolism but Increases Acetate Uptake in the Human Brain

    Science.gov (United States)

    Volkow, Nora D.; Kim, Sung Won; Wang, Gene-Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S.; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

    2012-01-01

    Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in thalamus. In contrast, alcohol intoxication caused a significant increase in [1-11C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in cerebellum and the smallest in thalamus. In heavy alcohol drinkers [1-11C]acetate brain uptake during alcohol challenge trended to be higher than in occasional drinkers (p <0.06) and the increases in [1-11C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-11C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (ie ketogenic diets) may have in alcoholics undergoing alcohol detoxification. PMID:22947541

  12. 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)

  13. Comparison of clinical types of Wilson's disease and glucose metabolism in extrapyramidal motor brain regions.

    Science.gov (United States)

    Hermann, W; Barthel, H; Hesse, S; Grahmann, F; Kühn, H-J; Wagner, A; Villmann, T

    2002-07-01

    In Wilson's disease a disturbed glucose metabolism especially in striatal and cerebellar areas has been reported. This is correlated with the severity of extrapyramidal motor symptoms (EPS). These findings are only based on a small number of patients. Up to now it is unknown whether EPS are caused by various patterns of disturbed basal ganglia glucose metabolism. We investigated 37 patients and 9 normal volunteers to characterize the disturbed glucose metabolism in Wilson's disease more precisely. The glucose metabolism was determined in 5 cerebellar and cerebral areas (putamen, caput nuclei caudati, cerebellum, midbrain and thalamic area) by using (18)F-Fluorodesoxyglucose-Positron-Emission-Tomography ( [(18)F]FDG-PET). The database was evaluated by a cluster analysis. Additionally, the severity extrapyramidal motor symptoms were judged by a clinical score system. Three characteristic patterns of glucose metabolism in basal ganglia were obtained. Two of them may be assigned to patients with neurological symptoms whereas the third cluster corresponds to most patients without EPS or normal volunteers. The clusters can be identified by characteristic consumption rates in this 5 brain areas. The severity of EPS can not clearly be assigned to one of the clusters with disturbed glucose metabolism. However, the most severe cases are characterized by the lowest consumption in the striatal area. When there is marked improvement of EPS impaired glucose consumption reveals a persistent brain lesion. Finally, the neurological symptoms in Wilson's disease are caused by (at least) two different patterns of disturbed glucose metabolism in basal ganglia and cerebellum. The severity of EPS seems to be determined by a disturbed consumption in the striatal area. PMID:12140675

  14. Cellular pathways of energy metabolism in the brain: is glucose used by neurons or astrocytes?

    Science.gov (United States)

    Nehlig, Astrid; Coles, Jonathan A

    2007-09-01

    Most techniques presently available to measure cerebral activity in humans and animals, i.e. positron emission tomography (PET), autoradiography, and functional magnetic resonance imaging, do not record the activity of neurons directly. Furthermore, they do not allow the investigator to discriminate which cell type is using glucose, the predominant fuel provided to the brain by the blood. Here, we review the experimental approaches aimed at determining the percentage of glucose that is taken up by neurons and by astrocytes. This review is integrated in an overview of the current concepts on compartmentation and substrate trafficking between astrocytes and neurons. In the brain in vivo, about half of the glucose leaving the capillaries crosses the extracellular space and directly enters neurons. The other half is taken up by astrocytes. Calculations suggest that neurons consume more energy than do astrocytes, implying that astrocytes transfer an intermediate substrate to neurons. Experimental approaches in vitro on the honeybee drone retina and on the isolated vagus nerve also point to a continuous transfer of intermediate metabolites from glial cells to neurons in these tissues. Solid direct evidence of such transfer in the mammalian brain in vivo is still lacking. PET using [(18)F]fluorodeoxyglucose reflects in part glucose uptake by astrocytes but does not indicate to which step the glucose taken up is metabolized within this cell type. Finally, the sequence of metabolic changes occurring during a transient increase of electrical activity in specific regions of the brain remains to be clarified. PMID:17659529

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

    International Nuclear Information System (INIS)

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U-14C]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

  16. 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.)

  17. 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.

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

    International Nuclear Information System (INIS)

    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 μmol hg-1 min-1. (author)

  19. 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...

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

    International Nuclear Information System (INIS)

    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

  1. 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.

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

    International Nuclear Information System (INIS)

    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 82Rb 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

  3. Formaldehyde Metabolism and Formaldehyde-induced Alterations in Glucose and Glutathione Metabolism of Cultured Brain Cells

    OpenAIRE

    Tulpule, Ketki

    2013-01-01

    Formaldehyde is an environmental pollutant that is also generated in the body during normal metabolic processes. Interestingly, several pathological conditions are associated with an increase in formaldehyde-generating enzymes in the body. The level of formaldehyde in the brain is elevated with increasing age and in neurodegenerative conditions which may contribute to lowered cognitive functions. Although the neurotoxic potential of formaldehyde is well established, the molecular mechanisms i...

  4. Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury

    Institute of Scientific and Technical Information of China (English)

    Yong Wook Kim; Hyoung Seop Kim; Young-Sil An; Sang Hee Im

    2010-01-01

    Background Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non-traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury.Methods We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scare. Statistical analysis was performed using statistical parametric mapping.Results Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule (Pcorrected <0.001), and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices (Pcorrected <0.001). In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices (Puncorrected <0.005).Conclusion Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism

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

    OpenAIRE

    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

    2015-01-01

    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 mo...

  6. 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)

    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-18FDG 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

  7. 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)

    Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S.; 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 (0.75 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-18FDG 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. PMID:25698759

  8. 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

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

    International Nuclear Information System (INIS)

    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

  10. D-(U-11C)glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V. (Karolinska Hospital and Institute, Stockholm (Sweden))

    1990-05-01

    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.

  11. Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain

    OpenAIRE

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

    2015-01-01

    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 durin...

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

    OpenAIRE

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

    2013-01-01

    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’ remains 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 ...

  13. Brain glucose metabolism and neuropsychological test in patients with mild cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    曹秋云; 江开达; 张明园; 刘永昌; 肖世富; 左传涛; 黄红芳

    2003-01-01

    Objective To investigate the features of regional cerebral metabolic rate of glucose (rCMRglc) in patients with mild cognitive impairment(MCI) by positron emission-tomography and its relationship with neuropsychological test.Methods Positron emission tomography, mini-mental state examination and Wechsler memory scale were applied in 10 patients with MCI and 10 healthy volunteers as the control group.Results Scores of mini-mental state examination and Wechsler memory scale in MCI patients were lower than those in the control group (P<0.01). rCMRglc of the left orbital gyrus, right middle temporal gyrus and right putamen was lower in the MCI group than in the control group (P<0.05). Correlation analysis in the MCI group indicated that rCMRglc of many brain regions such as the orbital gyrus, putamen, left hippocampus and parahippocampal gyrus, cingulate gyrus, left amygdaloid body, precentral gyrus, postcentral gyrus, and medial occipitotemporal gyrus in MCI patients, were correlated negatively with age; while the rCMRglc of many parts of the brain such as the left putamen, temporal lobe, anterior cingulate gyrus, left insular lobe, amygdaloid body, precentral gyrus, postcentral gyrus and medial occipitotemporal gyrus were correlated positively with mini-mental state examination; and rCMRglc of the left putamen, temporal lobe, left insular lobe, precentral gyrus and postcentral gyrus were correlated positively with Wechsler memory scale. The right putamen, the right inferior temporal gyrus, precentral gyrus, and left postcentral gyrus were correlated positively with the length of education. However, only rCMRglc of the left amygdaloid body were correlated positively with gender. Conclusion The rCMRglc was lower in the orbital gyrus and putamen of MCI patients. Their rCMRglc were correlated with their cognitive impairment severity, age, length of education and sex.

  14. 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 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.

  15. The Effects of Cocaine on Regional Brain Glucose Metabolism Is Attenuated in Dopamine Transporter Knockout Mice

    OpenAIRE

    Thanos, Panayotis K.; MICHAELIDES, MICHAEL; Benveniste, Helene; WANG, GENE JACK; Volkow, Nora D.

    2008-01-01

    Cocaine’s ability to block the dopamine transporter (DAT) is crucial for its reinforcing effects. However the brain functional consequences of DAT blockade by cocaine are less clear since they are confounded by its concomitant blockade of norepinephrine and serotonin transporters. To separate the dopaminergic from the non-dopaminergic effects of cocaine on brain function we compared the regional brain metabolic responses to cocaine between dopamine transporter deficient (DAT−/−) mice with tha...

  16. 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. PMID:26364049

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

    International Nuclear Information System (INIS)

    It could be shown using 14C-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 14C section thickness and exposure time could be established by means of densitometric measurement of brain sections of various thicknesses, by applying various 14C-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 14C-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 14C-deposition is in no way indicative of an increased metabolic activity, the possibility of quantifying 14C-tissue content provides a basis for estimating therapeutic effects e.g. in the treatment of trauma-caused brain edema. (orig.)

  18. 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

    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...... 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...

  19. Lactography as an approach to monitor glucose metabolism on-line in brain and muscle.

    Science.gov (United States)

    Korf, J; de Boer, J

    1990-01-01

    1. Thus far metabolic processes in the intact animal (or man) have been studied either by the analysis of body fluids, of biopsies, of tissue obtained post mortem or by techniques, requiring dedicated and expensive equipment (such as positron emission tomography or magnetic resonance spectroscopy). 2. Here we describe a relatively simple and inexpensive technique, that can be applied in vivo to study metabolism in brain regions and muscle in the freely moving rat and in human peripheral tissue. 3. The method is based on microdialysis allowing continuous sampling from the extracellular space, the enzymatic conversion of lactate and the on-line detection of fluorescent NADH. 4. Examples of the application of our technique include the monitoring of lactate efflux from various brain regions of behaving animals under a variety of stress exposures, during ischemia or hypoxia and drug treatments. 5. The results indicate that in brain lactate is not exclusively formed under hypoxia and that neuronal activation leads also to lactate formation, possibly due to the compartmentation of both the involved enzymes and the energy metabolism. 6. The increase of lactate formation in contracting or ischemic muscle or during exercise could also be followed on-line in the rat, suggesting that our approach allows the continuous monitoring of anaerobic metabolism in man e.g. during traumatic or arteriosclerotic limb ischemia or lactic acidosis in shock states. 7. The principle of our approach can easily be adapted to other metabolites, thus enabling to monitor other metabolic pathways in vivo as well. PMID:2276411

  20. 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.

  1. Age-related changes of glutathione content, glucose transport and metabolism, and mitochondrial electron transfer function in mouse brain

    International Nuclear Information System (INIS)

    To evaluate the oxidative stress-related parameters and to determine their order of appearance in the brain aging process, radionuclide experiments were carried out on male DBF1 mice at 3, 12, 24 and 30 months of age. The content of nonprotein sulfhydryl compounds, mainly glutathione, was estimated with technetium-99m meso-hexamethyl propyleneamine oxime ([99mTc]meso-HMPAO) tissue sampling. Glucose transport and metabolism was examined with [1-14C]2-deoxy-D-glucose (2-DG) tissue sampling. Mitochondrial electron transport function was estimated with [15O]O2 gas-tissue ARG. [99mTc]Meso-HMPAO uptake in brain expressed as standardized uptake value (SUV), (radioactivity in brain tissue/tissue weight)/(total administered radioactivity/body weight), reached maximum at 12 months of age and decreased at 24 and 30 months of age in every region examined. The pattern of 2-DG, expressed as SUV, showed a tendency to increase rather than decrease with aging. [15O]O2 fixation in brain slices remained constant until 24 months, while it decreased significantly at 30 months of age. The results suggested the possibility of using imaging techniques in vivo for longitudinal evaluation of the aging process and indicated reduction of nonprotein sulfhydryl compounds including GSH at the early stages of aging may also accelerate the dysfunction of mitochondrial electron transport and neurodegeneration

  2. Glucose Metabolic Brain Networks in Early-Onset vs. Late-Onset Alzheimer's Disease

    Science.gov (United States)

    Chung, Jinyong; Yoo, Kwangsun; Kim, Eunjoo; Na, Duk L.; Jeong, Yong

    2016-01-01

    Objective: Early-onset Alzheimer's disease (EAD) shows distinct features from late-onset Alzheimer's disease (LAD). To explore the characteristics of EAD, clinical, neuropsychological, and functional imaging studies have been conducted. However, differences between EAD and LAD are not clear, especially in terms of brain connectivity and networks. In this study, we investigated the differences in metabolic connectivity between EAD and LAD by adopting graph theory measures. Methods: We analyzed 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images to investigate the distinct features of metabolic connectivity between EAD and LAD. Using metabolic connectivity and graph theory analysis, metabolic network differences between LAD and EAD were explored. Results: Results showed the decreased connectivity centered in the cingulate gyri and occipital regions in EAD, whereas decreased connectivity in the occipital and temporal regions as well as increased connectivity in the supplementary motor area were observed in LAD when compared with age-matched control groups. Global efficiency and clustering coefficients were decreased in EAD but not in LAD. EAD showed progressive network deterioration as a function of disease severity and clinical dementia rating (CDR) scores, mainly in terms of connectivity between the cingulate gyri and occipital regions. Global efficiency and clustering coefficients were also decreased along with disease severity. Conclusion: These results indicate that EAD and LAD have distinguished features in terms of metabolic connectivity, with EAD demonstrating more extensive and progressive deterioration. PMID:27445800

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

    OpenAIRE

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

    2013-01-01

    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 aim at synthesiz...

  4. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease

    International Nuclear Information System (INIS)

    We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration. Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 ± 5 years, received FDG-PET examinations over 7 ± 2 years, and autopsy 6 ± 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 ± 3 years, received FDG-PET examinations over 3 ± 2 years, and autopsy 7 ± 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia. The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism. Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis. (orig.)

  5. Design of a sup 13 C (1H) RF probe for monitoring the in vivo metabolism of (1- sup 13 C)glucose in primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, B.E.; Sacks, W.; Bigler, R.E.; Hennessy, M.J.; Sacks, S.; Fleischer, A.; Zanzonico, P.B. (Intermagnetics General Corporation, Guilderland, NY (USA))

    1990-01-01

    The design of an RF probe suitable for obtaining proton-decoupled {sup 13}C spectra from a subhuman primate brain is described. Two orthogonal saddle coils, one tuned to the resonant frequency of {sup 13}C and the other to the resonant frequency of 1H, were used to monitor the in vivo metabolism of (1-{sup 13}C)glucose in rhesus monkey brain at 2.1 T. Difference spectra showed the appearance of {sup 13}C-enriched glutamate and glutamine 30 to 40 min after a bolus injection of (1-{sup 13}C)glucose.

  6. Brain glucose metabolic changes associated with chronic spontaneous Pain due to brachial plexus avulsion:a preliminary positron emission tomography study

    Institute of Scientific and Technical Information of China (English)

    CHEN Fu-yong; TAO Wei; CHENG Xin; WANG Hong-yan; HU Yong-sheng; ZHANG Xiao-hua; LI Yong-jie

    2008-01-01

    Background Previous brain imaging studies suggested that the brain activity underlying the perception of chronic pain maV differ from that underlying acute pain.To investigate the brain regions involved in chronic spontaneous pain due to brachial plexus avulsion(BPA),fluorine-18fluorodeoxygIucose (19F-FDG) positron emission tomography (PET) scanning was applied to determine the glucose metabolic changes in patients with pain due to BPA.Methods Six right-handed patients with chronic spontaneous pain due to left-BPA and twelve right-handed age-and sex-matched healthy control subjects participated in the 18F-FDG PET study.The patients were rated by visual analog scale (VAS) during scanning and Hamilton depression scale and Hamilton anxiety scale after scanning.Statistical parametric mapping 2 (SPM2) was applied for data analysis.Results Compared with healthy subjects,the patients had significant glucose metabolism decreases in the right thalamus and S I(P<0.001,uncorrected),and significant glucose metabolism increases in the right orbitofrontaI cortex (OFC) (BA11),left rostral insula cortex and left dorsolateral prefrontal codex (DLPFC) (BA10/46) (P<0.001,uncorrected).Conclusion These findings suggest that the brain areas involved in emotion.aRention and internal modulation of pain may be related to the chronic spontaneous pain due to BPA.

  7. Comparing brain amyloid deposition, glucose metabolism, and atrophy in mild cognitive impairment with and without a family history of dementia.

    Science.gov (United States)

    Mosconi, Lisa; Andrews, Randolph D; Matthews, Dawn C

    2013-01-01

    This study compares the degree of brain amyloid-β (Aβ) deposition, glucose metabolism, and grey matter volume (GMV) reductions in mild cognitive impairment (MCI) patients overall and as a function of their parental history of dementia. Ten MCI with maternal history (MH), 8 with paternal history (PH), and 24 with negative family history (NH) received 11C-PiB and 18F-FDG PET and T1-MRI as part of the Alzheimer's Disease Neuroimaging Initiative. Statistical parametric mapping, voxel based morphometry, and Z-score mapping were used to compare biomarkers across MCI groups, and relative to 12 normal controls. MCI had higher PiB retention, hypometabolism, and GMV reductions in Alzheimer-vulnerable regions compared to controls. Biomarker abnormalities were more pronounced in MCI with MH than those with PH and NH. After partial volume correction of PET, Aβ load exceeded hypometabolism and atrophy with regard to the number of regions affected and magnitude of impairment in those regions. Hypometabolism exceeded atrophy in all MCI groups and exceeded Aβ load in medial temporal and posterior cingulate regions of MCI MH. While all three biomarkers were abnormal in MCI compared to controls, Aβ deposition was the most prominent abnormality, with MCI MH having the greatest degree of co-occurring hypometabolism.

  8. 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

  9. Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography

    International Nuclear Information System (INIS)

    Cerebral glucose utilization (LCMRGI) was measured using the [18F]fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values normalized by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical abnormal values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant

  10. 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

  11. 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)

    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

  12. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia

    OpenAIRE

    Jingshu Xu; Paul Begley; Stephanie J. Church; Stefano Patassini; Selina McHarg; Nina Kureishy; Hollywood, Katherine A; Waldvogel, Henry J; Hong Liu; Shaoping Zhang; Wanchang Lin; Karl Herholz; Clinton Turner; Synek, Beth J.; Curtis, Maurice A.

    2016-01-01

    Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer’s disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem cas...

  13. 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)

    To study the effect of lipid depressing drugs on 18FDG myocardial concentration. The changes of 18FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18FDG 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 18FDG 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 18FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18FDG). The animals were killed 45 minutes following 18FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18FDG 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)

  14. Antihypertensive drugs and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Christos; V; Rizos; Moses; S; Elisaf

    2014-01-01

    Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

  15. 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)

    Fresh rat brain slices were incubated with 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degree C, and serial two-dimensional time-resolved images of [18F]FDG uptake were obtained from these specimens on imaging plates. The fractional rate constant (= k3*) of [18F]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)

  16. Parkinson's disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging

    Directory of Open Access Journals (Sweden)

    Laura K. Teune, MD, PhD

    2014-01-01

    Conclusion: We identified PD-related perfusion and metabolic brain patterns using PCASL and FDG-PET in the same patients which were comparable with results of existing research. In this respect, PCASL appears to be a promising addition in the early diagnosis of individual parkinsonian patients.

  17. 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

    Delayed structural cerebral sequelae has been reported following cranial radiation therapy (CRT) to children with primary brain tumors, but little is known about potential functional changes. Twenty-four patients were included, diagnosed and treated at a median age of 11 years, and examined after...... that there is a general reduction in rCMRglc in long-term recurrence free survivors of childhood primary brain tumors treated with CRT in high doses (44-56 Gy)......Delayed structural cerebral sequelae has been reported following cranial radiation therapy (CRT) to children with primary brain tumors, but little is known about potential functional changes. Twenty-four patients were included, diagnosed and treated at a median age of 11 years, and examined after...... 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...

  18. Correlation of brain cell glucose metabolism and patient's condition in children with epileptic encephalopathy An assessment using fluorine-18-fluoro-2-deoxy-D-glucose positron emission computed tomography

    Institute of Scientific and Technical Information of China (English)

    Qiongxiang Zhai; Yuxiong Guo; Yuxin Zhang; Zhihong Chen; Jian Ding; Juan Gui; Ying Hao

    2011-01-01

    We examined a total of 16 children with epileptic encephalopathy using fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission computed tomography (PET), magnetic resonance imaging (MRI) and electroencephalography.Children with infantile spasms showed significant mental retardation, severely abnormal electroencephalogram recordings, and bilateral diffuse cerebral cortex hypometabolism with 18F-FDG PET imaging.MRI in these cases showed brain atrophy, multi-micropolygyria, macrogyria, and porencephalia.In cases with Lennox-Gastaut syndrome, 18F-FDG PET showed bilateral diffuse glucose hypometabolism, while MRI showed cortical atrophy, heterotopic gray matter and tuberous sclerosis.MRI in cases with myoclonic encephalopathy demonstrated bilateral frontal and temporal cortical and white matter atrophy and 18F-FDG PET imaging showed bilateral frontal lobe atrophy with reduced bilateral frontal cortex, occipital cortex, temporal cortex and cerebellar glucose uptake.In children who could not be clearly classified, MRI demonstrated cerebral cortical atrophy and 18F-FDG PET exhibited multifocal glucose hypometabolism.Overall, this study demonstrated that the degree of brain metabolic abnormality was consistent with clinical seizure severity.In addition, 18F-FDG PET imaging after treatment was consistent with clinical outcomes.These findings indicate that 18F-FDG PET can be used to assess the severity of brain injury and prognosis in children with epileptic encephalopathy.

  19. Brain glucose metabolism is associated with hormone level in Cushing's disease: A voxel-based study using FDG-PET.

    Science.gov (United States)

    Liu, Shuai; Wang, Yinyan; Xu, Kaibin; Ping, Fan; Wang, Renzhi; Li, Fang; Cheng, Xin

    2016-01-01

    Chronic exposure to elevated levels of glucocorticoids can exert a neurotoxic effect in patients, possibly manifesting as molecular imaging alterations in patients. The aim of this study was to investigate the potential association between brain metabolism and elevated hormone level using (18)F-fluorodeoxyglucose positron emission tomography. We retrospectively enrolled 92 consecutive patients with confirmed diagnosis of Cushing's disease. A voxel-based analysis was performed to investigate the association between cerebral (18)F-fluorodeoxyglucose uptake and serum cortisol level. Relatively impaired metabolism of specific brain regions correlated with serum cortisol level was found. Specifically, notable correlations were found in the hippocampus, amygdala, and cerebellum, regions considered to be involved in the regulation and central action of glucocorticoids. Moreover, some hormone-associated regions were found in the frontal and occipital cortex, possibly mediating the cognitive changes seen in Cushing's disease. Our findings link patterns of perturbed brain metabolism relates to individual hormone level, thus presenting a substrate for cognitive disturbances seen in Cushing's disease patients, as well as in other conditions with abnormal cortisol levels.

  20. Brain glucose metabolism is associated with hormone level in Cushing's disease: A voxel-based study using FDG-PET.

    Science.gov (United States)

    Liu, Shuai; Wang, Yinyan; Xu, Kaibin; Ping, Fan; Wang, Renzhi; Li, Fang; Cheng, Xin

    2016-01-01

    Chronic exposure to elevated levels of glucocorticoids can exert a neurotoxic effect in patients, possibly manifesting as molecular imaging alterations in patients. The aim of this study was to investigate the potential association between brain metabolism and elevated hormone level using (18)F-fluorodeoxyglucose positron emission tomography. We retrospectively enrolled 92 consecutive patients with confirmed diagnosis of Cushing's disease. A voxel-based analysis was performed to investigate the association between cerebral (18)F-fluorodeoxyglucose uptake and serum cortisol level. Relatively impaired metabolism of specific brain regions correlated with serum cortisol level was found. Specifically, notable correlations were found in the hippocampus, amygdala, and cerebellum, regions considered to be involved in the regulation and central action of glucocorticoids. Moreover, some hormone-associated regions were found in the frontal and occipital cortex, possibly mediating the cognitive changes seen in Cushing's disease. Our findings link patterns of perturbed brain metabolism relates to individual hormone level, thus presenting a substrate for cognitive disturbances seen in Cushing's disease patients, as well as in other conditions with abnormal cortisol levels. PMID:27622138

  1. A proposed method for the determination of cerebral regional intermediary glucose metabolism in humans in vivo using specifically labeled 11C-glucose and positron emission transverse tomography (PETT). I. An animal model with 14C-glucose and rat brain autoradiography

    International Nuclear Information System (INIS)

    Based upon data obtained with our arterio-venous technique for the determination of cerebral metabolism in humans in vivo we have proposed a method for the determination of cerebral regional intermediary glucose metabolism in humans in vivo using specifically labeled 11C-glucose and positron emission transverse tomography (PETT). In it we would give the subject successive intravenous injections of [3,4-11C] glucose, [2,5-11C] glucose and [1-11C] glucose. There would be a 30 min period of continuous PETT measurements following each injection and a 2 hr interval after the first and second injections. The data would be used with suitable equations and algorithms to estimate for each specific region of the subject's brain the dynamics of the Embden-Meyerhof-Parnas (EMP) and the tricarboxylic acid cycle (TCA) metabolic pathways and the incorporation of glucose carbons into lactate, and the extent of dilution of glucose carbons into lactate, and the extent of dilution of glucose carbons in traversing the TCA with their subsequent incorporation into other carbon pools of the brain (ie, glutamate, glutamine, GABA, alanine). Using 14C as a model for 11C and autoradiographs made with rat brain slices, we have produced an animal model to demonstrate the feasibility of our proposed method. The resulting autoradiographs have provided evidence of the validity of the predictions made from our arterio-venous data. The model was employed to show the selective reductions in the rates of incorporation of specific carbon atoms of glucose into regions of the rat brain and evidence of altered metabolic pathways following a single electroconvulsive shock (ECS) and after a series of nine ECS

  2. In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography.

    Science.gov (United States)

    Rojas, Santiago; Herance, José Raúl; Gispert, Juan Domingo; Abad, Sergio; Torrent, Elia; Jiménez, Xavier; Pareto, Deborah; Perpiña, Unai; Sarroca, Sara; Rodríguez, Elisenda; Ortega-Aznar, Arantxa; Sanfeliu, Coral

    2013-07-01

    Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [(18)F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [(11)C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [(18)F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [(11)C]-PIB, and [(18)F]-Florbetapir could quantify the amyloid deposition in vivo and if [(18)F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [(18)F]-Florbetapir, [(11)C]-PIB, and [(18)F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [(18)F]-FDG is a consequence of glial activation that occurs in 5XFAD mice.

  3. A comparison between the impact of two types of dietary protein on brain glucose concentrations and oxidative stress in high fructose-induced metabolic syndrome rats

    OpenAIRE

    MADANI, ZOHRA; Malaisse, Willy J.; AIT-YAHIA, DALILA

    2015-01-01

    The present study explored the potential of fish proteins to counteract high glucose levels and oxidative stress induced by fructose in the brain. A total of 24 male Wistar rats consumed sardine protein or casein with or without high fructose (64%). After 2 months, brain tissue was used for analyses. The fructose rats exhibited an increase in body mass index (BMI), body weight, absolute and relative brain weights and brain glucose; however, there was a decrease in food and water intake. Fruct...

  4. Osteocalcin as a hormone regulating glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The number of patients with osteoporosis and diabetesis rapidly increasing all over the world. Bone is recentlyrecognized as an endocrine organ. Accumulatingevidence has shown that osteocalcin, which is specificallyexpressed in osteoblasts and secreted into the circulation,regulates glucose homeostasis by stimulating insulinexpression in pancreas and adiponectin expression inadipocytes, resulting in improving glucose intolerance.On the other hand, insulin and adiponectin stimulateosteocalcin expression in osteoblasts, suggesting thatpositive feedforward loops exist among bone, pancreas,and adipose tissue. In addition, recent studies haveshown that osteocalcin enhances insulin sensitivity andthe differentiation in muscle, while secreted factors frommuscle, myokines, regulate bone metabolism. Thesefindings suggest that bone metabolism and glucosemetabolism are associated with each other through theaction of osteocalcin. In this review, I describe the roleof osteocalcin in the interaction among bone, pancreas,brain, adipose tissue, and muscle.

  5. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Mosconi, Lisa [New York University School of Medicine, Department of Psychiatry, New York (United States); New York University School of Medicine, Center for Brain Health, MHL 400, New York, NY (United States); Mistur, Rachel; Switalski, Remigiusz; Glodzik, Lidia; Li, Yi; Pirraglia, Elizabeth; De Santi, Susan; Reisberg, Barry [New York University School of Medicine, Department of Psychiatry, New York (United States); Tsui, Wai Hon; De Leon, Mony J. [New York University School of Medicine, Department of Psychiatry, New York (United States); Nathan Kline Institute, Orangeburg, NY (United States); Wisniewski, Thomas [New York University School of Medicine, Department of Psychiatry, New York (United States); New York University School of Medicine, Department of Neurology, New York (United States); New York University School of Medicine, Department of Pathology, New York (United States)

    2009-05-15

    We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration. Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 {+-} 5 years, received FDG-PET examinations over 7 {+-} 2 years, and autopsy 6 {+-} 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 {+-} 3 years, received FDG-PET examinations over 3 {+-} 2 years, and autopsy 7 {+-} 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia. The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism. Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis. (orig.)

  6. 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...

  7. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    Science.gov (United States)

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

  8. 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.

  9. 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

    2016-01-01

    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. PMID:27763550

  10. Glucose metabolism in ischemic myocardium

    International Nuclear Information System (INIS)

    We determined the myocardial metabolic rate for glucose (MMRGlc) in the ischemic or infarcted myocardium using 18-F-fluorodeoxyglucose (18-FDG) with positron emission tomography (PET), and studied energy metabolism in the ischemic myocardium. In some cases, we compared glucose metabolism images by 18-FDG with myocardial blood flow images using 15-oxygen water. Two normal subjects, seven patients with myocardial infarction and four patients with angina pectoris were studied. Coronary angiography was performed within two weeks before or after the PET study to detect ischemic areas. PET studies were performed for patients who did not eat for 5 to 6 hours after breakfast. Cannulation was performed in the pedal artery to measure free fatty acid, blood sugar, and insulin. After recording the transmission scan for subsequent correction of photon attenuation, blood pool images were recorded for two min. after the inhalation of carbon monoxide (oxygen-15) which labeled the red blood cells in vivo. After 20 min., oxygen-15 water (15 to 20 mCi) was injected for dynamic scans, and flow images were obtained. Thirty min. after this procedure, 18-FDG (5 to 6 mCi) was injected, and 60 min later, a static scan was performed and glucose metabolism images were obtained. Arterial blood sampling for the time activity curve of the tracer was performed at the same time. According to the method of Phelps et al, MMRGlc was calculated in each of the region of interest (ROI) which was located in the left ventricular wall. MMRGlc obtained from each ROI was 0 to 17 mg/100 ml/min. In normal subjects MMRGlc was 0.4 to 7.3 mg/100 ml/min. In patients with myocardial infarction, it ranged from 3 to 5 mg/100 ml/min in the infarcted lesion. In patients with angina pectoris and subendocardial infarction, MMRGlc was 7 to 17 mg/100 ml/min in the ischemic lesion. In this lesion, myocardial blood flow was relatively low by oxygen-15 imagings (so-called mismatch). (J.P.N.)

  11. Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD

    Energy Technology Data Exchange (ETDEWEB)

    Mosconi, Lisa [University of Florence, Department of Clinical Pathophysiology, Nuclear Medicine Unit (Italy); University School of Medicine, Center for Brain Health, MHL400, Department of Psychiatry New York, New York, NY (United States)

    2005-04-01

    The demographics of aging suggest a great need for the early diagnosis of dementia and the development of preventive strategies. Neuropathology and structural MRI studies have pointed to the medial temporal lobe (MTL) as the brain region earliest affected in Alzheimer's disease (AD). MRI findings provide strong evidence that in mild cognitive impairments (MCI), AD-related volume losses can be reproducibly detected in the hippocampus, the entorhinal cortex (EC) and, to a lesser extent, the parahippocampal gyrus; they also indicate that lateral temporal lobe changes are becoming increasingly useful in predicting the transition to dementia. Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging has revealed glucose metabolic reductions in the parieto-temporal, frontal and posterior cingulate cortices to be the hallmark of AD. Overall, the pattern of cortical metabolic changes has been useful for the prediction of future AD as well as in distinguishing AD from other neurodegenerative diseases. FDG-PET on average achieves 90% sensitivity in identifying AD, although specificity in differentiating AD from other dementias is lower. Moreover, recent MRI-guided FDG-PET studies have shown that MTL hypometabolism is the most specific and sensitive measure for the identification of MCI, while the utility of cortical deficits is controversial. This review highlights cross-sectional, prediction and longitudinal FDG-PET studies and attempts to put into perspective the value of FDG-PET in diagnosing AD-like changes, particularly at an early stage, and in providing diagnostic specificity. The examination of MTL structures, which has so far been exclusive to MRI protocols, is then examined as a possible strategy to improve diagnostic specificity. All told, there is considerable promise that early and specific diagnosis is feasible through a combination of imaging modalities. (orig.)

  12. Impaired glucose metabolism treatment and carcinogenesis

    OpenAIRE

    MATYSZEWSKI, ARTUR; Czarnecka, Anna; Kawecki, Maciej; KORZEŃ, PIOTR; SAFIR, ILAN J.; Kukwa, Wojciech; SZCZYLIK, CEZARY

    2015-01-01

    Carbohydrate metabolism disorders increase the risk of carcinogenesis. Diabetes mellitus alters numerous physiological processes that may encourage cancer growth. However, treating impaired glucose homeostasis may actually promote neoplasia; maintaining proper glucose plasma concentrations reduces metabolic stresses, however, certain medications may themselves result in oncogenic effects. A number of previous studies have demonstrated that metformin reduces the cancer risk. However, the use o...

  13. 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.)

  14. 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...... of glucose uptake as visualized by functional brain imaging....

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

    Directory of Open Access Journals (Sweden)

    Thomas Abbruscato

    2012-10-01

    Full Text Available 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.

  16. Brain energy metabolism: development and application of novel live methodologies

    OpenAIRE

    Bennett, Rachel

    2012-01-01

    This thesis investigates methods of studying brain energy metabolism with a specific focus on the substrates oxygen and glucose. It details the in vitro development and in vivo characterisation of microelectrochemical sensors for the detection of brain tissue oxygen, and the in vivo characterisation of oxygen and glucose electrodes in the hippocampus utilising the technique of long-term in vivo electrochemistry (LIVE). Chapter 1 introduces the brain, energy metabolism and neurochemical ana...

  17. 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)

    Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [18F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB1) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D2 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 [18F]MK-9470, [18F]FDG and [11C]raclopride. Relative glucose metabolism and parametric CB1 receptor and D2 binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2). In the QA model, [18F]MK-9470 uptake, glucose metabolism and D2 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). [18F]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 CB1 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 CB1 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, D2 and CB1 neurotransmission in the contralateral hemisphere. (orig.)

  18. Glucose metabolism of lactobacillus divergens

    International Nuclear Information System (INIS)

    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 25oC 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-14C]-glucose was included to correct for endogenous product dilution

  19. Glucose Metabolism in Mentally Retarded Children

    International Nuclear Information System (INIS)

    Glucose metabolism has been studied in normal, mentally retarded and hypothyroid children who exhibited subnormal I.Q. in spite of an adequate thyroxine dose. Two parameters, the breath and the blood, were examined. Continuous breath analysis following intravenous glucose-U-14C was carried out to examine its end product 14CO2. Blood was analysed half-hourly for the specific activity of glucose in this pool. Data are presented in terms of stable carbon dioxide expiration rate, the maximum specific activity of carbon dioxide attained, the glucose pool of the body and its turnover rate. (author)

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

    International Nuclear Information System (INIS)

    We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered [18F]fluorodeoxyglucose (FDG) and [14C]-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 14C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the 14C 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

  1. Effect of latent asymptomatic toxoplasmosis on glucose metabolism in brain of mice%弓形虫慢性感染对小鼠脑内葡萄糖代谢影响的研究

    Institute of Scientific and Technical Information of China (English)

    周永华; 黄洪波; 陶永辉; 俞惠新; 许永良; 张英; 高琪

    2011-01-01

    Objective To explore the effect of latent asymptomatic Toxoplasma gondii infection on glucose metabolism in brain of mice. Methods Twenty mice were randomly divided into two groups: a Toxoplasma infected group and normal control group. The mice in the Toxoplasma infected group were inoculated with 0.3 ml of brain suspension in saline containing ten Toxoplasma gondii tissue cysts, avirulent Toxoplasma gondii Prugniaud (PRU, a Type II strain). The mice in the control group received 0.3 ml of saline orally. Six monthes after the infection, the glucose metabolism changes in the mouse brain were evaluated by Mi-croPET, then all the mice were sacrificed and the brain tissues were observed histopathologically. Results Compared with the normal controls, the infected mice demonstrated profound and widespread brain pathology, and MicroPET indicated a significant glucose metabolism reduction in the brain of asymptomatic Toxoplasma gondii infected mice. Conclusion Chronic Toxoplasma gondii infection maybe results in the glucose metabolism reduction in the brain of mice.%目的 探讨弓形虫慢性感染对小鼠脑内葡萄糖代谢的影响.方法 将30只SPF级ICR小鼠随机分成弓形虫感染组和正常对照组,感染组每只小鼠口服感染弓形虫PRU株包囊悬液0.3 ml(含包囊10个),对照组口服0.3 ml生理盐水.小鼠感染弓形虫6个月后,应用MicroPET扫描脑内葡萄糖代谢,结束后解剖小鼠进行脑组织病理学观察.结果 与正常对照组小鼠相比,弓形虫慢性感染6个月后,“无症状”的感染小鼠脑内葡萄糖代谢均显著下降,脑组织中可见大小不一、数量不等的包囊,脑膜下有大量淋巴细胞浸润、血管充血、小血管淋巴细胞袖管形成.结论 弓形虫慢性感染可造成宿主脑内葡萄糖代谢下降,神经元变性或细胞丢失.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Lee, Dong Soo; Kang, Eun Joo; Seo, Jeong Kee; Yeo, Jeong Seok; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2001-06-01

    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.

  3. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

    OpenAIRE

    Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 ...

  4. 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. PMID:27461005

  5. In Alzheimer’s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial

    Science.gov (United States)

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke; Møller, Arne; Hansen, Søren B.; Vang, Kim; Rodell, Anders; Brændgaard, Hans; Gottrup, Hanne; Schacht, Anna; Møller, Niels; Brock, Birgitte; Rungby, Jørgen

    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 in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means in precuneus (P = 0.009, 3.2 μmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (P = 0.04, 2.1 μmol/hg/min, 95% CI: 4.21; 0.081), temporal (P = 0.046, 1.54 μmol/hg/min, 95% CI: 3.05; 0.030), and occipital (P = 0.009, 2.10 μmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (P = 0.04, 1.54 μmol/hg/min, 95% CI: 3.01; 0.064). In contrast, the GLP-1 analog treatment caused a numerical but insignificant increase of CMRglc after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMRglc that signifies cognitive impairment, synaptic dysfunction, and disease evolution. We draw no firm conclusions from the Aβ load or cognition measures, for which the study was underpowered. PMID:27252647

  6. The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism.

    Science.gov (United States)

    Thompson, Garth J; Riedl, Valentin; Grimmer, Timo; Drzezga, Alexander; Herman, Peter; Hyder, Fahmeed

    2016-07-01

    The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI "nuisance signals" were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a "nuisance signal," also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states. PMID:27029438

  7. 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...... be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better...

  8. Metabolic costs and evolutionary implications of human brain development.

    Science.gov (United States)

    Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas

    2014-09-01

    The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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 ...

  14. Metabolic pathways for glucose in astrocytes.

    Science.gov (United States)

    Wiesinger, H; Hamprecht, B; Dringen, R

    1997-09-01

    Cultured astroglial cells are able to utilize the monosaccharides glucose, mannose, or fructose as well as the sugar alcohol sorbitol as energy fuel. Astroglial uptake of the aldoses is carrier-mediated, whereas a non-saturable transport mechanism is operating for fructose and sorbitol. The first metabolic step for all sugars, including fructose being generated by enzymatic oxidation of sorbitol, is phosphorylation by hexokinase. Besides glucose only mannose may serve as substrate for build-up of astroglial glycogen. Whereas glycogen synthase appears to be present in astrocytes as well as neurons, the exclusive localization of glycogen phosphorylase in astrocytes and ependymal cells of central nervous tissue correlates well with the occurrence of glycogen in these cells. The identification of lactic acid rather than glucose as degradation product of astroglial glycogen appears to render the presence of glucose-6-phosphatase in cultured astrocytes an enigma. The colocalization of pyruvate carboxylase, phosphenolpyruvate carboxykinase and fructose-1,6-bisphosphatase points to astrocytes as being the gluconeogenic cell type of the CNS. PMID:9298844

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

    Science.gov (United States)

    Zhang, Rong; Zhang, Tong; Ali, Ali Muhsen; Al Washih, Mohammed; Pickard, Benjamin; Watson, David G

    2016-01-01

    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. PMID:27076878

  16. BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

    OpenAIRE

    Cunnane, SC; NUGENT, S; Roy, M.; Courchesne-Loyer, A; Croteau, E; Tremblay, S.; Castellano, A.; Pifferi, F.; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; M. Allard; Barberger-Gateau, P

    2010-01-01

    Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may in...

  17. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

    Science.gov (United States)

    Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

  18. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia***

    Institute of Scientific and Technical Information of China (English)

    Xiaoliang Shu; Yongsheng Zhang; Han Xu; Kai Kang; Donglian Cai

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance fol owing ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions fol owing cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de-crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy-ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor fol owing cerebral ischemia may be involved in the development of glucose intolerance.

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

    Energy Technology Data Exchange (ETDEWEB)

    Schroeck, H.K.; Kuschinsky, W. (Univ. of Bonn (Germany, F.R.))

    1989-10-01

    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.

  20. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

    OpenAIRE

    Ma, Ya-Hong; Yu, Caiguo; Kayoumu, Abudurexiti; Guo, Xin; Ji, Zhili; Liu, George

    2015-01-01

    Abstract Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia...

  1. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study

    OpenAIRE

    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; Julian N Trollor; Perminder S Sachdev

    2014-01-01

    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 volum...

  2. Longitudinal Studies of Cerebral Glucose Metabolism in Late-Life Depression and Normal Aging

    Science.gov (United States)

    Marano, Christopher M.; Workman, Clifford I.; Kramer, Elisse; Hermann, Carol R.; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David; Smith, Gwenn S.

    2014-01-01

    Objective Late-life depression (LLD) has a substantial public health impact and is both a risk factor for and prodrome of dementia. Positron Emission Tomography (PET) studies of cerebral glucose metabolism have demonstrated sensitivity in evaluating neural circuitry involved in depression, aging, incipient cognitive decline and dementia. The present study evaluated the long term effects of a course of antidepressant treatment on glucose metabolism in LLD patients. Methods Nine LLD patients and 7 non-depressed control subjects underwent clinical and cognitive evaluations as well as brain magnetic resonance imaging and PET studies of cerebral glucose metabolism at baseline, after 8 weeks of treatment with citalopram for a major depressive episode (patients only), and at an approximately 2 year follow-up. Results The majority of LLD patients were remitted at follow-up (7/9). Neither patients nor controls showed significant cognitive decline. The patients showed greater increases in glucose metabolism than the controls in regions associated with mood symptoms (anterior cingulate and insula). Both groups showed decreases in metabolism in posterior association cortices implicated in dementia. Conclusions Longitudinal changes in cerebral glucose metabolism are observed in controls and LLD patients without significant cognitive decline that are more extensive than the decreases in brain volume. Longer duration follow-up studies and the integration of other molecular imaging methods will have implications for understanding the clinical and neurobiological significance of these metabolic changes. PMID:22740289

  3. Metabolic therapy: a new paradigm for managing malignant brain cancer.

    Science.gov (United States)

    Seyfried, Thomas N; Flores, Roberto; Poff, Angela M; D'Agostino, Dominic P; Mukherjee, Purna

    2015-01-28

    Little progress has been made in the long-term management of glioblastoma multiforme (GBM), considered among the most lethal of brain cancers. Cytotoxic chemotherapy, steroids, and high-dose radiation are generally used as the standard of care for GBM. These procedures can create a tumor microenvironment rich in glucose and glutamine. Glucose and glutamine are suggested to facilitate tumor progression. Recent evidence suggests that many GBMs are infected with cytomegalovirus, which could further enhance glucose and glutamine metabolism in the tumor cells. Emerging evidence also suggests that neoplastic macrophages/microglia, arising through possible fusion hybridization, can comprise an invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells, as well as for the more rapidly proliferating cancer stem cells. Therapies that increase inflammation and energy metabolites in the GBM microenvironment can enhance tumor progression. In contrast to current GBM therapies, metabolic therapy is designed to target the metabolic malady common to all tumor cells (aerobic fermentation), while enhancing the health and vitality of normal brain cells and the entire body. The calorie restricted ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic metabolic therapy that also reduces fermentable fuels in the tumor microenvironment. Metabolic therapy, as an alternative to the standard of care, has the potential to improve outcome for patients with GBM and other malignant brain cancers. PMID:25069036

  4. 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.

  5. 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

    2016-05-01

    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. PMID:27133169

  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

    OpenAIRE

    Jing Jiang; Kai Gao; Yuan Zhou; Anping Xu; Suhua Shi; Gang Liu; Zhigang Li

    2015-01-01

    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 ...

  7. Lactate as a cerebral metabolic fuel for glucose-6-phosphatase deficient children.

    Science.gov (United States)

    Fernandes, J; Berger, R; Smit, G P

    1984-04-01

    The main substrates for brain energy metabolism were measured in blood samples taken from the carotid artery and the internal jugular bulb of four children with glycogen storage disease caused by deficiency of glucose-6-phosphatase. Multiple paired arterial and venous blood samples were analyzed for glucose, lactate, pyruvate, D-beta-hydroxybutyrate, acetoacetate, glycerol and O2, and the arteriovenous differences of the concentrations were calculated. In the first three patients the substrates were measured in two successive conditions with lower and higher glucose-intake, respectively, inducing reciprocally higher and lower concentrations of blood lactate. In the fourth patient medium chain triglycerides were administered simultaneously with the glucose-containing gastric drip feeding. Lactate appeared to be taken up significantly. It consumed, if completely oxidized, between 40-50% of the total O2 uptake in most cases. Only once in one patient the uptake of lactate switched to its release, when the blood lactate level decreased to normal. D-beta-hydroxybutyrate and acetoacetate arteriovenous (A-V) differences were small to negligible and these ketone bodies, therefore, did not contribute substantially to the brain's energy expenditure. Glycerol was not metabolized by the brain. Lactate thus appeared to be the second brain fuel next to glucose. It may protect the brain against fuel depletion in case of hypoglycemia.

  8. 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...... and metabolism was originally performed using the Kety-Schmidt method and this method still represent the gold standard by which subsequent methods have been evaluated. However, in its classical setting, the method overestimates cerebral blood flow. Studies of metabolic changes during activation must take...... difficulties due to limitation in resolution and partial volume effects. In contrast to the tight coupling between regional glucose metabolism and cerebral blood flow, there is an uncoupling between flow and oxygen consumption as the latter only increases to a limited extend. The excess glucose uptake is thus...

  9. A comparative study in Alzheimer's and normal brains of trace element distribution using PIXE and INA analyses and glucose metabolism by positron emission tomography

    NARCIS (Netherlands)

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

    1999-01-01

    The onset of Alzheimer's disease has been shown to affect trace element concentrations in the brain when compared to "normal" subjects in ex vivo samples. The techniques used to determine trace element concentrations were proton-induced X-ray emission and instrumental neutron activation analysis. Wi

  10. 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.

  11. Elevated glucose metabolism in the amygdala during an inhibitory avoidance task

    OpenAIRE

    Sandusky, Leslie A.; Flint, Robert W.; McNay, Ewan C.

    2013-01-01

    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 previ...

  12. 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.

  13. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults.

    Directory of Open Access Journals (Sweden)

    Emmanuel Maganga

    Full Text Available Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART, yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7% vs.11/153 (7.2%, p<0.001 and frank diabetes mellitus (27/150 (18.0% vs. 8/153 (5.2%, p = 0.001 than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78-11.77, p<0.001. Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.

  14. 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.

  15. 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....

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

    International Nuclear Information System (INIS)

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

  17. 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. PMID:26908609

  18. 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

    mellitus. GLP-1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging preclinical findings indicate a potential neuroprotective role of the peptide, e.g., in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis......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 diabetes...

  19. Intra- and intercellular mechanisms regulating glucose metabolism in the liver.

    NARCIS (Netherlands)

    E. Casteleijn (Eric)

    1988-01-01

    textabstractThe regulation of glucose metabolism in the liver by intraand intercellular mechanisms was studied. Fructose-1,6-bisphosphatase, an enzyme involved in de novo synthesis of glucose was found to be stimulated by glucagon in isolated parenchym~l liver cells. Glucagon increased the Vmax of f

  20. 2维和3维采集对脑葡萄糖代谢半定量指标的影响%Effect on Semiquantitive Analysis for Brain Glucose Metabolism with 2 or 3 Dimensional PET Scan Respectively

    Institute of Scientific and Technical Information of China (English)

    苏玉盛; 马云川; 李德鹏; 张琳瑛; 尚建文

    2001-01-01

    目的研究2维(2D)和3维(3D)采集对脑葡萄糖代谢半定量指标有无明显影响,在实际工作中可否灵活采用.方法 36例无神经疾病病史、症状和体征;脑磁共振成像无异常的受检者分为2组,其中2D组15例,3D组21例.静脉注射18F-FDG后行PET脑断层显像,经计算机滤波反投影重建获得横断面、冠状面、矢状面断层影像.横断面影像经处理层厚为0.5cm,按常规分别选取代表双侧额叶、顶叶、颞叶、枕叶、小脑皮质的三层影像,勾画出各结构的边界,依据体重和注射剂量等参数求出平均SUV值.将上述各部位的平均SUV值进行左右比较,计算出比值,称R(L/R).将各脑叶的平均SUV值与小脑平均SUV值进行比较,计算出比值,称R(C/Cb).上述数据进行统计学处理.结果 2D和3D两组双侧额叶、顶叶、颞叶、枕叶、小脑皮质的平均SUV值,R(L/R)和R(C/Cb)皆差异无显著性.结论 2D和3D采集各有优缺点,当采用SUV作为半定量指标对脑葡萄糖代谢状况进行评价时,两种采集方式对结果无明显影响,故可根据实际情况,灵活选择不同的采集方式.%objective To explore the effect on semiquantitive analysis for brain glucose metabolism with 2 or 3 dimensional PET scan respectively.Methods 36 normal persons were divided into two group,15 for 2D,21 for 3D.PET scans were done after 40 minutes of injection of FDG .The transaxial,the coronal,the saggital were gotten through computer reconstruction. The transaxial slice density was 0.5cm. The borders ofbilateral frontal lobes , bilateral parietal lobes , bilateral tempt lobes ,bilateral occipital lobes and bilateral cerebellum were drawn. According to ROI, weight and injection dose of FDG,mean SUVs in all above lobes were gotten. R(L/R)s from Mean SUVs in the left lobes via those in the right were caculated. R(C/CB)s from mean SUVs in different brain lobes via those different

  1. Glucose and galactose metabolism in Gluconabacter liquefaciens

    NARCIS (Netherlands)

    Stouthamer, A.H.

    1961-01-01

    Glucose-grown cells of Gluconobacter liquefaciens oxidize glucose, gluconate and 2-ketogluconate practically completely to 2,5-diketogluconate by particulate enzymes, localized in the protoplasmic membrane. The bulk of the 2,5-diketgluconate (and 5-ketogluconate) enters the cytoplasm and is metaboli

  2. Evaluation of glucose metabolism in women with multiple ovarian follicles

    Institute of Scientific and Technical Information of China (English)

    Shulan Lü; Xiaoyan Guo; Zuansun Cao; Wenjun Mao

    2007-01-01

    Objective:To investigate glucose metabolism in women with multiple ovarian follicles (MOF) and explore the relationship between glucose metabolism, insulin resistance and body weight. Methods:We evaluated 46 women with MFO and 30 nor mal women as controls. All the subjects were given 75g of glucose orally in order to perform the oral glucose tolerance test(OGTT) and insulin releasing test(IRT), and they were also evaluated for insulin resistance using the insulin resistance index with homeostatic model assessment (HOMA). Results:The occurrence of impaired glucose tolerance in women with MOF was 10.87%, which was significantly higher than that in the control group (3.33% ,P < 0.05). The rate of insulin resistance was 30.43% in the study group as compared to 10.00% in the control group. The results showed that there was significant difference between the two groups(P < 0.05). The levels of FSH,LH,PRL,E2,T and P between the two groups had no significant difference (P > 0.05). BMI in women with impaired glucose tolerance was correlated positively to insulin resistance (r =0.567, P < 0.05). Conclusion :Abnormal glucose metabolism was observed in women with unitary multiple ovarian follicles,and this could be attributed to obesity and insulin resistance. Women with MOF and associated obesity should be subjected to OGTT so that their glucose levels can be monitored as a preventive measure.

  3. Peripheral glucose metabolism and insulin sensitivity in Alzheimer's disease.

    Science.gov (United States)

    Kilander, L; Boberg, M; Lithell, H

    1993-04-01

    Twenty-four patients with Alzheimer's disease and matched controls were examined with reference to metabolic parameters such as peripheral insulin and glucose metabolism, serum lipid concentrations and blood pressure levels. Blood glucose levels and insulin response were measured during an intravenous glucose tolerance test and peripheral insulin sensitivity was estimated with the hyperinsulinemic euglycemic clamp technique. There were no differences recorded between the two groups in glucose metabolism, triglyceride, cholesterol or HDL-cholesterol levels. The patients with Alzheimer's disease had significantly lower blood pressure levels, which partly could be explained by ongoing treatment with neuroleptics and antidepressives. Previous findings of higher insulin levels in Alzheimer's disease could not be verified. PMID:8503259

  4. 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

  5. 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; Francesco, Ursini; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Torniolo, 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. PMID:27631200

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr. (Univ. of California, Irvine (USA)); Gillin, J.C. (Univ. of California, San Diego (USA))

    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.

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

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    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

  9. Effects of nicotine on regional cerebral glucose metabolism in awake resting tobacco smokers.

    Science.gov (United States)

    Domino, E F; Minoshima, S; Guthrie, S K; Ohl, L; Ni, L; Koeppe, R A; Cross, D J; Zubieta, J

    2000-01-01

    Eleven healthy tobacco smoking adult male volunteers of mixed race were tobacco abstinent overnight for this study. In each subject, positron emission tomographic images of regional cerebral metabolism of glucose with [18F]fluorodeoxyglucose were obtained in two conditions in the morning on different days: about 3min after approximately 1-2mg of nasal nicotine spray and after an equivalent volume of an active placebo spray of oleoresin of pepper in a random counterbalanced design. A Siemens/CTI 931/08-12 scanner with the capability of 15 horizontal brain slices was used. The images were further converted into a standard uniform brain format in which the mean data of all 11 subjects were obtained. Images were analysed in stereotactic coordinates using pixel-wise t statistics and a smoothed Gaussian model. Peak plasma nicotine levels varied three-fold and the areas under the curve(0-30min) varied seven-fold among the individual subjects. Nicotine caused a small overall reduction in global cerebral metabolism of glucose but, when the data were normalized, several brain regions showed relative increases in activity. Cerebral structures specifically activated by nicotine (nicotine minus pepper, Z score >4.0) included: left inferior frontal gyrus, left posterior cingulate gyrus and right thalamus. The visual cortex, including the right and left cuneus and left lateral occipito-temporal gyrus fusiformis, also showed an increase in regional cerebral metabolism of glucose with Z scores >3. 6. Structures with a decrease in regional cerebral metabolism of glucose (pepper minus nicotine) were the left insula and right inferior occipital gyrus, with Z scores >3.5. Especially important is the fact that the thalamus is activated by nicotine. This is consistent with the high density of nicotinic cholinoceptors in that brain region. However, not all brain regions affected by nicotine are known to have many nicotinic cholinoceptors. The results are discussed in relation to the

  10. 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.

  11. Glucose metabolism in cultured trophoblasts from human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H. (Washington Univ., St. Louis, MO (United States))

    1990-02-26

    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 {sup 14}C-labeled glucose and reactions were stopped by addition of perchloric acid. {sup 14}CO{sub 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 {sup 14}C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO{sub 2} by the phosphogluconate (PG) pathway was estimated from specific yields of {sup 14}CO{sub 2} from (1-{sup 14}C)-D-glucose and (6-{sup 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.

  12. 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...

  13. 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

    2016-01-01

    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 18F-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. PMID:27574485

  14. Serum Visfatin Levels, Adiposity and Glucose Metabolism in Obese Adolescents

    OpenAIRE

    Taşkesen, Derya; Kirel, Birgül; Us, Tercan

    2012-01-01

    Objective: Visfatin, an adipokine, has insulin-mimetic effects. The main determinants of both the production and the physiologic role of visfatin are still unclear. The aim of this study is to determine the relation of serum visfatin to adiposity and glucose metabolism. Methods: 40 pubertal adolescents (20 females, 20 males; age range: 9-17 years) with exogenous obesity and 20 age- and sex-matched healthy adolescents (10 females, 10 males) were enrolled in the study. Oral glucose tolerance te...

  15. The metabolism of malate by cultured rat brain astrocytes

    International Nuclear Information System (INIS)

    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

  16. Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism.

    Science.gov (United States)

    Murai, Hideki; Suzuki, Yukihisa; Kiyosawa, Motohiro; Wakakura, Masato; Mochizuki, Manabu; Ishiwata, Kiichi; Ishii, Kenji

    2011-01-01

    A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides. The severity of the blepharospasm was evaluated by PET scanning using the Wakakura classification. Sixteen women (mean age 42.4 ± 11.7 years) were examined as normal controls. The thalamic glucose metabolism in our patient was significantly increased on days 149, 212, and 688. The severity of the blepharospasm was positively correlated with the thalamic glucose metabolism, suggesting that the severity of blepharospasms reflects thalamic activity. PMID:22110436

  17. 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 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....

  18. Glucose metabolism in rats submitted to skeletal muscle denervation

    OpenAIRE

    Wilton Marlindo Santana Nunes; Maria Alice Rostom de Mello

    2005-01-01

    This study analyzed the local and systemic effects of immobilization by denervation of the skeletal muscle on glucose metabolism. The rats were submitted to section of the right paw sciatic nerve. A reduction was observed in glucose uptake by the isolated soleus muscle of the denervated paw after 3 and 7 days, but not after 28 days in relation to the control animals. There was no difference after 3 and 7 days in glucose uptake by the soleus muscle of the opposite intact paw in relation to the...

  19. Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study

    International Nuclear Information System (INIS)

    Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and glucose metabolism (CMRGlc) were measured using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO2 was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is impaired and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy. (orig.). With 1 fig., 4 tabs

  20. Effects of hyperammonemia on brain energy metabolism

    DEFF Research Database (Denmark)

    Schousboe, Arne; Waagepetersen, Helle S.; Leke, Renata;

    2014-01-01

    The literature related to the effects of elevated plasma ammonia levels on brain energy metabolism is abundant, but heterogeneous in terms of the conclusions. Thus, some studies claim that ammonia has a direct, inhibitory effect on energy metabolism whereas others find no such correlation...... but related to the fact that hepatic encephalopathy is always associated with reduced brain activity, a condition clearly characterized by a decreased CMRO2. Whether this may be related to changes in GABAergic function remains to be elucidated....

  1. Glucose regulates lipid metabolism in fasting king penguins.

    Science.gov (United States)

    Bernard, Servane F; Orvoine, Jord; Groscolas, René

    2003-08-01

    This study aims to determine whether glucose intervenes in the regulation of lipid metabolism in long-term fasting birds, using the king penguin as an animal model. Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo before, during, and after a 2-h glucose infusion under field conditions. All the birds were in the phase II fasting status (large fat stores, protein sparing) but differed by their metabolic and hormonal statuses, being either nonstressed (NSB; n = 5) or stressed (SB; n = 5). In both groups, glucose infusion at 5 mg.kg-1.min-1 induced a twofold increase in glycemia. In NSB, glucose had no effect on lipolysis (maintenance of plasma concentrations and rates of appearance of glycerol and nonesterified fatty acids) and no effect on the plasma concentrations of triacylglycerols (TAG), glucagon, insulin, or corticosterone. However, it limited fatty acid (FA) oxidation, as indicated by a 25% decrease in the plasma level of beta-hydroxybutyrate (beta-OHB). In SB, glucose infusion induced an approximately 2.5-fold decrease in lipolytic fluxes and a large decrease in FA oxidation, as reflected by a 64% decrease in the plasma concentration of beta-OHB. There were also a 35% decrease in plasma TAG, a 6.5- and 2.8-fold decrease in plasma glucagon and corticosterone, respectively, and a threefold increase in insulinemia. These data show that in fasting king penguins, glucose regulates lipid metabolism (inhibition of lipolysis and/or of FA oxidation) and affects hormonal status differently in stressed vs. nonstressed individuals. The results also suggest that in birds, as in humans, the availability of glucose, not of FA, is an important determinant of the substrate mix (glucose vs. FA) that is oxidized for energy production. PMID:12738609

  2. Metabolic Brain-Computer Interfaces

    OpenAIRE

    Sitaram, Ranganatha

    2010-01-01

    Brain-Computer Interfaces (BCI) utilise neurophysiological signals originating in the brain to activate or deactivate external devices or computers (Donoghue 2002; Wolpaw, Birbaumer et al. 2002; Nicolelis 2003; Birbaumer and Cohen 2007). The neuronal signals can be recorded from inside the brain (invasive BCIs) or outside (non-invasive BCIs) of the brain. Most BCIs developed so far have used operant training of direct neuroelectric responses, Electroencephalography (EEG) waves, event-related ...

  3. Over-estimation of glucose-6-phosphatase activity in brain in vivo. Apparent difference in rates of [2-3H]glucose and [U-14C]glucose utilization is due to contamination of precursor pool with 14C-labeled products and incomplete recovery of 14C-labeled metabolites

    International Nuclear Information System (INIS)

    Significant dephosphorylation of glucose 6-phosphate due to glucose-6-phosphatase activity in rat brain in vivo was recently reported. The evidence was an apparent more rapid 3H than 14C loss from the glucose pool and faster [2-3H]glucose than [U-14C]glucose utilization following pulse labeling of the brain with [2-3H,U-14C]glucose. Radiochemical purity of the glucose and quantitative recovery of the labeled products of glucose metabolism isolated from the brain were obviously essential requirements of their study, but no evidence for purity and recovery was provided. When we repeated these experiments with the described isolation procedures, we replicated the results, but found that: 1) the precursor glucose pool contained detritiated, 14C-labeled contaminants arising from glucose metabolism, particularly 2-pyrrolidone-5-carboxylic acid derived from [14C]glutamine; 2) [14C]glucose metabolite were not quantitatively recovered; 3) the procedure used to isolate the glucose itself produced detritiated, 14C-labeled derivatives of [2-3H,U-14C]glucose. These deficiencies in the isolation procedures could fully account for the observations that were interpreted as evidence of significant glucose 6-phosphate dephosphorylation by glucose-6-phosphatase activity. When glucose was isolated by more rigorous procedures and its purity verified in the present studies, no evidence for such activity in rat brain was found

  4. Glucose metabolism and effect of acetate in ovine adipocytes.

    Science.gov (United States)

    Yang, Y T; White, L S; Muir, L A

    1982-08-01

    Isolated ovine adipocytes were incubated in vitro with specifically labeled 14C-glucose in the presence or absence of acetate. The flux patterns of glucose carbon through major metabolic pathways were estimated. When glucose was added as the sole substrate, approximately equal portions of glucose carbon (10%) were oxidized to CO2 in the pentose phosphate pathway, in the pyruvate dehydrogenase reaction and in the citrate cycle. Fifteen percent of the glucose carbon was incorporated into fatty acids and 43% was released as lactate and pyruvate. Addition of acetate to the medium increased glucose carbon uptake by 1.5-fold. Most of this increase was accounted for by a sevenfold increase in the activity of the pentose phosphate pathway. Acetate increased glucose carbon fluxes via pentose phosphate pathway to triose phosphates, from triose phosphate to pyruvate, into glyceride glycerol, into lactate and pyruvate and into pyruvate dehydrogenase and citrate cycle CO2. Glucose carbon incorporated into fatty acids was decreased 50% by acetate while, carbon fluxes through the phosphofructokinase-aldolase reactions were not significantly increased. Results of this study suggest that, when glucose is the sole substrate, the conversion of glucose to fatty acids in ovine adipocytes may not be limited by the maximum capacity of hexokinase, the pentose phosphate pathway or enzymes involved in the conversion of triose phosphates to pyruvate and of pyruvate to fatty acid. Acetate increased glucose utilization apparently by increasing activity of the pentose phosphate pathway as a result of enhanced NADPH utilization for fatty acid synthesis. PMID:7142048

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-07-01

    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-(/sup 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.

  6. Effect of intracarotid injection of iopamidol on local cerebral glucose utilization in rat brain.

    Science.gov (United States)

    d'Avella, D; Cicciarello, R; Albiero, F; Piscitelli, G; Fiori, M G; Mesiti, M; Princi, P; d'Aquino, S

    1989-01-01

    We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of intracarotid injection of a nonionic, low-osmolar contrast medium (iopamidol) on local cerebral glucose utilization in the rat brain. Contrast medium was injected at 20 degrees C and at 37 degrees C, and the relative changes in local cerebral glucose utilization were measured. At 20 degrees C the viscosity of the contrast agent was about twice that of the same solution at 37 degrees C, and resulted in a statistically significant increase in local cerebral glucose utilization in the hemisphere ipsilateral to the side of intracarotid infusion. Saline control studies showed that the metabolic change was not related to either the solution temperature or the osmolality. These findings suggest that increased viscosity of a contrast medium may contribute to its neurotoxic effects during cerebral angiography, hence emphasizing the importance of preheating contrast material to avoid adverse reactions.

  7. Acute effects of ghrelin administration on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Djurhuus, Christian Born; Gjedsted, Jakob;

    2007-01-01

    CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single-blind, p...

  8. Fluorine-18-fluorodeoxyglucose assessment of glucose metabolism in bone tumors

    NARCIS (Netherlands)

    Kole, AC; Nieweg, OE; Hoekstra, HJ; van Horn, [No Value; Hoops, HS; Vaalburg, W

    1998-01-01

    In our study, we investigate the glucose metabolism of various types of bone lesions with F-18-fluorodeoxyglucose (FDG) PET. Methods: Twenty-six patients showing clinical and radiographic symptoms of a malignant bone tumor were included. Histological examination after the PET study revealed 19 malig

  9. The impact of Vitamin D Replacement on Glucose Metabolism

    OpenAIRE

    H, Parildar; O, Cigerli; DA, Unal; O, Gulmez; NG, Demirag

    2013-01-01

    Objective: We investigated the impact of vitamin D supplementation on glucose metabolism in Vitamin D-deficient patients with prediabetes. Methods: A total of 66 subjects with the mean ages 52.2±9.9 years were included in this prospective and a 6-month follow-up study between 2008-2010. Vitamin D deficient patients (

  10. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

    Directory of Open Access Journals (Sweden)

    Suzan Wopereis

    Full Text Available BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. METHODOLOGY: To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. CONCLUSIONS: Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.

  11. CMPF does not associate with impaired glucose metabolism in individuals with features of metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Maria A Lankinen

    Full Text Available 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF is a metabolite produced endogenously from dietary sources of furan fatty acids. The richest source of furan fatty acids in human diet is fish. CMPF was recently shown to be elevated in fasting plasma in individuals with gestational diabetes and type 2 diabetes, and mechanistically high level of CMPF was linked to β cell dysfunction. Here we aimed to study the association between plasma CMPF level and glucose metabolism in persons with impaired glucose metabolism.Plasma CMPF concentration was measured from plasma samples of the study participants in an earlier controlled dietary intervention. All of them had impaired glucose metabolism and two other characteristics of the metabolic syndrome. Altogether 106 men and women were randomized into three groups for 12 weeks with different fish consumption (either three fatty fish meals per week, habitual fish consumption or maximum of one fish meal per week. Associations between concentration of CMPF and various glucose metabolism parameters at an oral glucose tolerance test at baseline and at the end of the study were studied.Fasting plasma CMPF concentration was significantly increased after a 12-week consumption of fatty fish three times per week, but the concentration remained much lower compared to concentrations reported in diabetic patients. Increases of plasma CMPF concentrations mostly due to increased fish consumption were not associated with impaired glucose metabolism in this study. Instead, elevated plasma CMPF concentration was associated with decreased 2-hour insulin concentration in OGTT.Moderately elevated concentration of CMPF in plasma resulting from increased intake of fish is not harmful to glucose metabolism. Further studies are needed to fully explore the role of CMPF in the pathogenesis of impaired glucose metabolism.ClinicalTrials.gov NCT00573781.

  12. 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.

  13. Glucose metabolism in sheep fed grass supplemented with gliricidia sepium

    International Nuclear Information System (INIS)

    The limiting factor on improving ruminant production for most of the available feed in developing countries are low in quality. Therefore high fibre diet must be supplemented by high nutritive feed such as leguminous trees that much available in those regions. Gliricidia sepium was one of very potential candidates. Glucose as a major energy source in fed animals required precursor in form of propionate and amino acids from diet. Those precursors might be supplied by these legume leaves. The aim of this research was to investigate the glucose metabolism in the sheep fed grass supplemented by Gliricidia sepium. Fifteens sheep (18 months old) were used in the experiment. These are were divided into three groups that fed by experimental diet of Mitchell grass (MG group), Gliricidia (GS group), and MG supplemented with GS (MGGS group). D-[U-14C]glucose infusate was infused continuously through the left jugular venous catheter of each animal to measure glucose metabolism in those sheeps measurements were done on feed utilisation and glucose metabolism. The results indicated that there was an improvement in efficiency of feed utilisation in the MGGS group as reflected by lower feed conversion ratio by the group. Plasma glucose concentration profile per unit of OM intake were similar for GS and MGGS groups, but higher than that in the MG group (P<0.01). Glucose entry rate (GER) increased in MG group through GS to the MGGS group, while N retention accordingly was increased. It can be concluded that the utilisation of GS by the ruminant animal could be improved by feeding it with a low quality feed at a ratio of 40:60 (GS:Low quality feed) to achieve an NI:DOMI ratio of 0.03 - 0.04. This improvement would be manifested in increasing DOMI, with subsequent increase in GER or net protein deposition as might be expressed in positive N retention. (author)

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

    International Nuclear Information System (INIS)

    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

  15. Evidence that brain glucose availability influences exercise-enhanced extracellular 5-HT level in hippocampus: a microdialysis study in exercising rats.

    Science.gov (United States)

    Béquet, F; Gomez-Merino, D; Berthelot, M; Guezennec, C Y

    2002-09-01

    The relationship between brain glucose and serotonin is still unclear and no direct evidence of an action of brain glucose on serotonergic metabolism in central fatigue phenomena has been shown yet. In order to determine whether or not brain glucose could influence the brain 5-hydroxytryptamine (5-HT) system, we have monitored in microdialysis the effects of a direct injection of glucose in rat brain hippocampus on serotonergic metabolism [i.e. 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan (TRP)], during high intensive treadmill running. The injection was performed just before and after exercise. We have shown that glucose induced a decrease of brain 5-HT levels to a minimum of 73.0 +/- 3.5% of baseline after the first injection (P exercise-induced 5-HT enhanced levels. We have observed the same phenomenon concerning the 5-HIAA, but brain TRP levels were not decreased by the injections. In conclusion, this study demonstrates that brain glucose can act on serotonergic metabolism and thus can prevent exercise-induced increase of 5-HT levels. The results also suggest that extracellular brain glucose does not act on the synthesis way of 5-HT, but probably on the release/reuptake system. PMID:12193220

  16. Metabolic correlates of hominid brain evolution.

    Science.gov (United States)

    Leonard, William R; Robertson, Marcia L; Snodgrass, J Josh; Kuzawa, Christopher W

    2003-09-01

    Large brain sizes in humans have important metabolic consequences as humans expend a relatively larger proportion of their resting energy budget on brain metabolism than other primates or non-primate mammals. The high costs of large human brains are supported, in part, by diets that are relatively rich in energy and other nutrients. Among living primates, the relative proportion of metabolic energy allocated to the brain is positively correlated with dietary quality. Humans fall at the positive end of this relationship, having both a very high quality diet and a large brain size. Greater encephalization also appears to have consequences for aspects of body composition. Comparative primate data indicate that humans are 'under-muscled', having relatively lower levels of skeletal muscle than other primate species of similar size. Conversely, levels of body fatness are relatively high in humans, particularly in infancy. These greater levels of body fatness and reduced levels of muscle mass allow human infants to accommodate the growth of their large brains in two important ways: (1) by having a ready supply of stored energy to 'feed the brain', when intake is limited and (2) by reducing the total energy costs of the rest of the body. Paleontological evidence indicates that the rapid brain evolution observed with the emergence of Homo erectus at approximately 1.8 million years ago was likely associated with important changes in diet and body composition. PMID:14527625

  17. Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

    OpenAIRE

    Mark Lambie; James Chess; Jun-Young Do; Hyunjin Noh; Hi-Bahl Lee; Yong-Lim Kim; Angela Summers; Paul Ford Williams; Sara Davison; Marc Dorval; Nick Topley; Simon John Davies

    2016-01-01

    Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a ...

  18. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

    Institute of Scientific and Technical Information of China (English)

    Ya-Hong Ma; Caiguo Yu; Abudurexiti Kayoumu; Xin Guo; Zhili Ji; George Liu

    2015-01-01

    Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH.However,it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance.In this study,we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice.ApoCⅢ transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring:maternal non-transgenic control and maternal transgenic offspring,and paternal control and paternal transgenic offspring.Plasma triglycerides (TG),total cholesterol (TC),fasting plasma glucose (FPG) and fasting insulin (FINS) were measured.ApoCⅢ overexpression caused severe hypertriglyceridemia,but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups.The 4 groups of offspring had similar birth weight and growth rate.The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice,but there was no difference in plasma TG between maternal and paternal transgenic offspring.Although the FPG of the 4 groups of animals had no difference,the maternal transgenic mice showed impaired glucose tolerance,increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups.In conclusion,maternally inherited hypertriglyceridemia in ApoCⅢ transgenic mice displayed impaired glucose tolerance,hyperinsulinemia and increased HOMA-R,while paternally inherited hypertriglyceridemia did not have such impacts.

  19. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning

    OpenAIRE

    Linnman, Clas; Zeidan, Mohamed A.; Pitman, Roger K.; Milad, Mohammed R.

    2011-01-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differ...

  20. In vivo Dynamic Studies of Brain Metabolism

    Institute of Scientific and Technical Information of China (English)

    LUO Xuechun; JIANG Yufeng; ZHANG Riqing

    2005-01-01

    Nuclear magnetic resonance (NMR) can noninvasively monitor intracellular concentrations and kinetic properties of numerous inorganic and organic compounds. A 31P NMR surface coil was used in vivo to dynamically measure phosphocreatine (PCr), adenosine triphosphate (ATP), and intracellular inorganic phosphate (Pi) levels in mouse brain during ischemia-reperfusion to study the damage of cerebral tissues caused by ischemia and effects of herbs on cerebral energy metabolism during ischemia-reperfusion. The study provides dynamic brain energy metabolism data during different periods. The data show that some herbs more rapidly increase the PCr level during the recovery phase than in the control group.

  1. Regional differences of relationships between atrophy and glucose metabolism of cerebral cortex in patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    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

  2. 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. PMID:27182841

  3. Cerebral metabolism of glucose in benign hereditary chorea

    International Nuclear Information System (INIS)

    Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by chorea of early onset with little or no progression. There is marked clinical variability in this disease with some subjects having onset in infancy and others with onset in early adulthood. In contrast to Huntington's disease (HD), there is no dementia. Computed tomography is normal in all subjects with no evidence of caudate nucleus atrophy. We present the results of positron emission tomography using 18F-2-fluorodeoxyglucose on three patients with this disorder from two families. Cerebral glucose metabolism in one patient was decreased in the caudate nucleus, as previously reported in HD. The other two persons from a second family showed a relative decrease in metabolic rates of glucose in the caudate when compared with the thalamus. It appears that caudate hypometabolism is not specific for HD. These findings suggest that the caudate nucleus may play a significant role in the pathophysiology of some persons with BHC

  4. Exploring Temporospatial Changes in Glucose Metabolic Disorder, Learning, and Memory Dysfunction in a Rat Model of Diffuse Axonal Injury

    OpenAIRE

    Jia LI; Gu, Lei; FENG, DONG-FU; Ding, Fang; Zhu, Guangyao; Rong, Jiandong

    2012-01-01

    Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and contributes significantly to cognitive deficits. The mechanisms underlying these cognitive deficits are often associated with complex metabolic alterations. However, the relationships between temporospatial alterations in cerebral glucose metabolism and the pathophysiology of DAI-related learning and memory dysfunction are not yet completely understood. We used a small animal positron emission tomograph...

  5. 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....

  6. Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism

    OpenAIRE

    Murai, Hideki; Suzuki, Yukihisa; Kiyosawa, Motohiro; Wakakura, Masato; Mochizuki, Manabu; Ishiwata, Kiichi; Ishii, Kenji

    2011-01-01

    A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides. The severity of the blepharospasm was evaluated by PET scanning using the Waka...

  7. Skeleton and Glucose Metabolism: A Bone-Pancreas Loop

    OpenAIRE

    2015-01-01

    Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteopr...

  8. Glucose challenge test (50-g GCT) in detection of glucose metabolism disorders in peritoneal dialysis patients: preliminary study

    OpenAIRE

    Madziarska, Katarzyna; Zmonarski, Slawomir; Penar, Jozef; Krajewska, Magdalena; Mazanowska, Oktawia; Augustyniak-Bartosik, Hanna; Gołebiowski, Tomasz; Klak, Renata; Weyde, Waclaw; Klinger, Marian

    2014-01-01

    Background The aim was to evaluate the clinical utility of the oral glucose tolerance screening test (50-g GCT—glucose challenge test) for the detection of glucose metabolism disorders (GMD) in peritoneal dialysis (PD) patients with normal fasting glucose levels. Methods The 50-g GCT was performed in 20 prevalent patients without history of diabetes before PD treatment onset, who had been on dialysis for a median time of 15.34 months. In addition, other indicators of glucose metabolism were m...

  9. A glucose fuel cell for implantable brain-machine interfaces.

    Directory of Open Access Journals (Sweden)

    Benjamin I Rapoport

    Full Text Available We have developed an implantable fuel cell that generates power through glucose oxidation, producing 3.4 μW cm(-2 steady-state power and up to 180 μW cm(-2 peak power. The fuel cell is manufactured using a novel approach, employing semiconductor fabrication techniques, and is therefore well suited for manufacture together with integrated circuits on a single silicon wafer. Thus, it can help enable implantable microelectronic systems with long-lifetime power sources that harvest energy from their surrounds. The fuel reactions are mediated by robust, solid state catalysts. Glucose is oxidized at the nanostructured surface of an activated platinum anode. Oxygen is reduced to water at the surface of a self-assembled network of single-walled carbon nanotubes, embedded in a Nafion film that forms the cathode and is exposed to the biological environment. The catalytic electrodes are separated by a Nafion membrane. The availability of fuel cell reactants, oxygen and glucose, only as a mixture in the physiologic environment, has traditionally posed a design challenge: Net current production requires oxidation and reduction to occur separately and selectively at the anode and cathode, respectively, to prevent electrochemical short circuits. Our fuel cell is configured in a half-open geometry that shields the anode while exposing the cathode, resulting in an oxygen gradient that strongly favors oxygen reduction at the cathode. Glucose reaches the shielded anode by diffusing through the nanotube mesh, which does not catalyze glucose oxidation, and the Nafion layers, which are permeable to small neutral and cationic species. We demonstrate computationally that the natural recirculation of cerebrospinal fluid around the human brain theoretically permits glucose energy harvesting at a rate on the order of at least 1 mW with no adverse physiologic effects. Low-power brain-machine interfaces can thus potentially benefit from having their implanted units

  10. Metabolism Kinetics of Glucose in Anchorage-dependent Cell Cultures

    Institute of Scientific and Technical Information of China (English)

    孙祥明; 张元兴

    2001-01-01

    The kinetic model of glucose metabolism was established and successfully applied to batchcultures of rCHO and rBHK cells. It was found that a large amount of glucose was utilized for cellmaintenance, and the overwhelming majority of maintenance energy from glucose was by its anaerobicmetabolism in both rBHK and rCHO cell cultures. The overall maintenance coefficients from aerobicmetabolism were 1.9×10-13 mmol/(cell.h) for rCHO cells and 7×10-13 mmol/(cell.h) for rBHK cells. Inaddition, all Go/T and Eo/T gradually increased with the same trend as the cell growth in the culture ofboth rCHO and rBHK cells. The overall molecule yield coefficients of lactate to glucose were 1.61 for rCHO cells and 1.38 for rBHK cells. The yield coefficients of cell to glucose were 4.5×108 cells/mmol for rCHO cells and 1.9 × 108 cells/mmol for rBHK cells, respectively.

  11. EXPLORING THE MECHANISM OF ACUPUNCTURE IN THE TREATMENT OF STROKE FROM CHANGES OF GLUCOSE METABOLISM IN THE CEREBRAL MOTOR CENTER

    Institute of Scientific and Technical Information of China (English)

    石现; 左芳; 关玲

    2004-01-01

    Objective:To observe the effect of acupuncture on cerebral glucose metabolism in stroke patients.Methods:Changes of cerebral glucose metabolism before and after acupuncture stimulation were observed in six cases of stroke patients by using positron emission tomography (PET) scanner. Electroacupuncture (EA,4 Hz, continuous waves and duration of 20 min) was applied to Baihui (百会GV 20) and right Qubin (曲鬓GB 7). 18 Fluorine deoxyglucose (18FDG), a developer (radioactive form of glucose) for showing the levels of the brain functional activity was given to the patients intravenously. SPM software was used to deal with the data of each pixel point by unilateral t-test (Ts: P=0.05), then, the regions showing increase/decrease of the glucose metabolism were obtained.Results:After acupuncture stimulation, significant increase of glucose metabolism was found to be in the first somatic motor cortical region (MI), supplementary motor area (SMA), premotor area (PMC), and the superior parietal lobule (LPs) on the healthy side of the brain; while the decrease of glucose metabolism found in MI, PMC and LPs on the focus side. In addition to the cerebral regions related to the motor function, changes of glucose metabolism were also found in the parietal lobule and basal ganglion area, central parietal gyrus, superior parietal gyrus, putamen, cerebellum, etc..Conclusion:Acupuncture of Qubin (GB 7) and Baihui (GV 20) can activate motor-related cerebral structures in the bilateral cerebral hemisphere and induce excitement reaction of the potentially correlative motor area so as to compensate or assist the injured motor area to play a role in improving motor function in stroke patients.

  12. Angiotensin Receptor Blockade Increases Pancreatic Insulin Secretion and Decreases Glucose Intolerance during Glucose Supplementation in a Model of Metabolic Syndrome

    OpenAIRE

    Rodriguez, Ruben; Viscarra, Jose A.; Minas, Jacqueline N.; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M.

    2012-01-01

    Renin-angiotensin system blockade improves glucose intolerance and insulin resistance, which contribute to the development of metabolic syndrome. However, the contribution of impaired insulin secretion to the pathogenesis of metabolic syndrome is not well defined. To assess the contributions of angiotensin receptor type 1 (AT1) activation and high glucose intake on pancreatic function and their effects on insulin signaling in skeletal muscle and adipose tissue, an oral glucose tolerance test ...

  13. Metabolic changes in the brain

    International Nuclear Information System (INIS)

    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.)

  14. 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. PMID:27001278

  15. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    Directory of Open Access Journals (Sweden)

    Jin Shao

    2015-01-01

    Full Text Available Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG, sclerostin (SOST, and Dickopf (DKK which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, such as osteocalcin (OCN, which promotes proliferation of β cells, insulin secretion, and insulin sensitivity. Additionally OCN can also regulate the fat cells and male gonad endocrine activity and be regulated by insulin and the neural system. In summary, skeleton has endocrine function via OCN and plays an important role in energy metabolism, especially in glucose metabolism.

  16. Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans

    DEFF Research Database (Denmark)

    Lerche, Susanne; Brock, Birgitte; Rungby, Jørgen;

    2008-01-01

    demonstrated 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 may also protect the brain by limiting intracerebral glucose fluctuation when plasma glucose is increased.......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...

  17. Seasonal Temperature Changes Do Not Affect Cardiac Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Jukka Schildt

    2015-01-01

    Full Text Available FDG-PET/CT is widely used to diagnose cardiac inflammation such as cardiac sarcoidosis. Physiological myocardial FDG uptake often creates a problem when assessing the possible pathological glucose metabolism of the heart. Several factors, such as fasting, blood glucose, and hormone levels, influence normal myocardial glucose metabolism. The effect of outdoor temperature on myocardial FDG uptake has not been reported before. We retrospectively reviewed 29 cancer patients who underwent PET scans in warm summer months and again in cold winter months. We obtained myocardial, liver, and mediastinal standardized uptake values (SUVs as well as quantitative cardiac heterogeneity and the myocardial FDG uptake pattern. We also compared age and body mass index to other variables. The mean myocardial FDG uptake showed no significant difference between summer and winter months. Average outdoor temperature did not correlate significantly with myocardial SUVmax in either summer or winter. The heterogeneity of myocardial FDG uptake did not differ significantly between seasons. Outdoor temperature seems to have no significant effect on myocardial FDG uptake or heterogeneity. Therefore, warming the patients prior to attending cardiac PET studies in order to reduce physiological myocardial FDG uptake seems to be unnecessary.

  18. Morphological and glucose metabolism abnormalities in alcoholic Korsakoff's syndrome: group comparisons and individual analyses.

    Directory of Open Access Journals (Sweden)

    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.

  19. Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia

    International Nuclear Information System (INIS)

    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)

  20. Walking speed and brain glucose uptake are uncoupled in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    John H. Kindred

    2015-02-01

    Full Text Available Motor impairments of the upper and lower extremities are common symptoms of multiple sclerosis (MS. While some peripheral effects like muscle weakness and loss of balance have been shown to influence these symptoms, central nervous system activity has not been fully elucidated. The purpose of this study was to determine if alterations in glucose uptake were associated with motor impairments in patients with multiple sclerosis. Eight patients with multiple sclerosis (4 men and 8 sex matched healthy controls performed 15 minutes of treadmill walking at a self-selected pace, during which ≈ 322 MBq of the positron emission tomography glucose analogue [18F]-Fluorodeoxyglucose was injected. Immediately after the cessation of walking, participants underwent positron emission tomography imaging. Patients with MS had lower FDG uptake in ≈ 40% of the brain compared to the healthy controls (pFWE-corr -0.75, P < 0.032. Within patients with MS only 3 of the 15 regions showed significant correlations: insula (r = -0.74, P = 0.036, hippocampus (r = -0.72, P = 0.045, and calcarine sulcus (r = -0.77, P = 0.026. This data suggests that walking impairments in patients with MS may be due to network wide alterations in glucose metabolism. Understanding how brain activity and metabolism are altered in patients with MS may allow for better measures of disability and disease status within this clinical population.

  1. A comprehensive metabolic profile of cultured astrocytes using isotopic transient metabolic flux analysis and 13C-labeled glucose

    Directory of Open Access Journals (Sweden)

    Ana I Amaral

    2011-09-01

    Full Text Available Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA to estimate intracellular fluxes of cultured astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time-points were then analyzed by mass spectrometry and/or HPLC. Metabolic fluxes were estimated by fitting a carbon labeling network model to isotopomer profiles experimentally determined. Both the fast isotopic equilibrium of glycolytic metabolite pools and the slow labeling dynamics of TCA cycle intermediates are described well by the model. The large pools of glutamate and aspartate which are linked to the TCA cycle via reversible aminotransferase reactions are likely to be responsible for the observed delay in equilibration of TCA cycle intermediates. Furthermore, it was estimated that 11% of the glucose taken up by astrocytes was diverted to the pentose phosphate pathway. In addition, considerable fluxes through pyruvate carboxylase (PC (PC/pyruvate dehydrogenase (PDH ratio = 0.5, malic enzyme (5% of the total pyruvate production and catabolism of branched-chained amino acids (contributing with ~40% to total acetyl-CoA produced confirmed the significance of these pathways to astrocytic metabolism. Consistent with the need of maintaining cytosolic redox potential, the fluxes through the malate-aspartate shuttle and the PDH pathway were comparable. Finally, the estimated glutamate/α-ketoglutarate exchange rate (~0.7 µmol.mg prot-1.h-1 was similar to the TCA cycle flux. In conclusion, this work demonstrates the potential of isotopic transient MFA for a comprehensive analysis of

  2. 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....

  3. Metabolic profile of normal glucose-tolerant subjects with elevated 1-h plasma glucose values

    Science.gov (United States)

    Pramodkumar, Thyparambil Aravindakshan; Priya, Miranda; Jebarani, Saravanan; Anjana, Ranjit Mohan; Mohan, Viswanathan; Pradeepa, Rajendra

    2016-01-01

    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. PMID:27730069

  4. Glucose metabolism alterations in patients with bipolar disorder.

    Science.gov (United States)

    Rosso, Gianluca; Cattaneo, Annamaria; Zanardini, Roberta; Gennarelli, Massimo; Maina, Giuseppe; Bocchio-Chiavetto, Luisella

    2015-09-15

    Patients with bipolar disorder (BD) are more frequently affected by metabolic syndrome (MetS) than the general population, but the neurobiological correlates underlying such association are still not clarified and few studies in BD have evaluated the role of regulators of lipid and glucose metabolism. The present study was aimed to investigate putative alterations in markers linked to metabolic dysfunctions as C-peptide, Ghrelin, GIP, GLP-1, Glucagon, Insulin, Leptin, PAI-1 (total), Resistin and Visfatin in a sample of BD patients compared to controls. Furthermore, associations between changes of metabolic markers and relevant clinical features, such as severity of symptomatology, number and type of past mood episodes, drug treatments and presence/absence of metabolic alterations (MetS, diabetes and cardiovascular disease) were analyzed. A total of 57 patients with BD and 49 healthy controls were recruited. The main results showed lower serum levels of Glucagon, GLP-1, Ghrelin, and higher levels of GIP in BD patients as compared to controls (p = 0.018 for Ghrelin; p < 0.0001 for Glucagon; p < 0.0001 for GLP-1; p < 0.0001 for GIP). Further, Glucagon and GLP-1 levels were significantly associated with the number of past mood episodes. These findings support the hypothesis that alterations in Glucagon, GLP-1, GIP and Ghrelin might be involved in BD pathogenesis and might represent useful biomarkers for the development of preventive and personalized therapies in this disorder. PMID:26120808

  5. Regional cerebral glucose metabolism in frontotemporal lobar degeneration

    International Nuclear Information System (INIS)

    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

  6. 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

  7. 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.

  8. Glucose metabolism in rats submitted to skeletal muscle denervation

    Directory of Open Access Journals (Sweden)

    Wilton Marlindo Santana Nunes

    2005-07-01

    Full Text Available This study analyzed the local and systemic effects of immobilization by denervation of the skeletal muscle on glucose metabolism. The rats were submitted to section of the right paw sciatic nerve. A reduction was observed in glucose uptake by the isolated soleus muscle of the denervated paw after 3 and 7 days, but not after 28 days in relation to the control animals. There was no difference after 3 and 7 days in glucose uptake by the soleus muscle of the opposite intact paw in relation to the control. There was increased glucose uptake in the same paw 28 days after denervation. The rate of glucose removal in response to exogenous insulin after 28 days of denervation was significantly higher than in control animals and those observed after 3 and 7 days of denervation. These results suggest that immobilization by denervation interfered not only in glucose metabolism in the skeletal muscle involved but also in other tissues.O estudo analisou os efeitos locais e sistêmicos da imobilização por desnervação do músculo esquelético sobre o metabolismo glicidico. Ratos foram submetidos à secção do nervo ciático da pata direita. Observou-se redução da captação de glicose pelo músculo sóleo isolado da pata desnervada após 3 e 7 mas não após 28 dias em relação a animais controle. Não houve diferença após 3 e 7 dias na captação de glicose pelo músculo sóleo da pata contralateral intacta em relação ao controle. Houve aumento da captação de glicose nesta mesma pata 28 dias após a desnervação. A taxa de remoção da glicose em resposta à insulina exógena após 28 dias de desnervação foi significantemente superior à do controle e àquelas observadas após 3 e 7 dias da desnervação. Esses resultados sugerem que a imobilização por desnervação interfere não só no metabolismo da glicose no músculo esquelético envolvido como também em outros tecidos.

  9. The estrogen hypothesis of schizophrenia implicates glucose metabolism

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D;

    2008-01-01

    . 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...

  10. 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.

  11. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder.

    Science.gov (United States)

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; Hollywood, Katherine A; Jüllig, Mia; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

    2016-06-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. PMID:26957286

  12. 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.

  13. PROTON MR SPECTROSCOPY IN BRAIN METABOLIC DISORDERS

    Directory of Open Access Journals (Sweden)

    Nicola De Stefano

    2012-01-01

    Full Text Available Metabolic disorders of the central nervous system (CNS include pathologies with extremely different pathogenesis. The clinical diagnosis of these disorders is often very difficult and requires sophisticated laboratory investigations. Proton magnetic resonance (MR spectroscopy (1H-MRS has been recently used in a number of clinical studies to supplement conventional MRI as it is able to provide in vivo biochemical assay of a given brain tissue. Brain data on several neurometabolic diseases suggest that 1H-MRS can provide in vivo chemical-pathological characterization of the abnormality detected by MRI and can detect metabolic alterations in tissue appearing normal on conventional MRI. This may help for differential diagnosis and can be important in the evaluation of disease outcome. Indices provided by 1H-MRS have been demonstrated to be relevant to patients’ clinical status, to represent sensitive indicators of early neurological involvement and to be helpful in monitoring effects of therapeutic interventions. This suggests that, in the next future, a more extensive use of brain 1H-MRS in the management of patients with metabolic disorders affecting CNS should be encouraged.

  14. 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...

  15. Rapid, transient drop in brain glucose after intravenous phloretin or 3-0-methyl-D-glucose.

    Science.gov (United States)

    Oldendorf, W H; Crane, P D; Lawner, P M; Braun, L D

    1983-01-01

    Rats were injected intravenously with either phloretin (100 mg/kg) or 3-0-methyl glucose (2 g/kg) to reduce the carrier-mediated flux of glucose into brain. Plasma glucose and brain free glucose (BFG), lactate, and glycogen were measured over a 16 min time course. Injection of these substances caused a rapid drop in BFG to 60% of control at one minute and a minimum (50% of control values) at 4 min., followed by a gradual rise to control levels at 16 min. While plasma glucose fell, and then increased after injection, brain lactate and glycogen content was unaffected. Repeated injections of phloretin eventually caused a drop in brain glycogen; but with either competitor, BFG never fell below 50% of normal values. The i.v. injection of the glucose analog, 3-0-methyl glucose (the less toxic of the two drugs) is proposed as a possible means of cutting off the potentially hazardous supply of blood glucose to the postischemic brain.

  16. Biochemical Hypermedia: Glucose as a Central Molecule in Metabolism

    Directory of Open Access Journals (Sweden)

    J.K. Sugai

    2008-05-01

    Full Text Available The technologies of information, together with education resources, have been pointed out as a solution to the improvement of teaching approach, but they still claim for programs to fulfill the demands of didactic materials. So, a biochemical software was developed aiming to contribute for the better understanding of the glycolysis. It was prepared with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. The introduction screen shows a teacher in a theater presenting glucose as a central molecule in the metabolism of animals, plants and many microorganisms. She invites for a better knowledge of glucose through a view of its discovery and its metabolism. A step by step animation process shows the interaction of glucose in aerobic conditions with the enzymes of the glycolytic pathways and its products. An explanation text of each enzyme catalytic process is provided by links. A static pathway is always available through a link. The fates of pyruvate yielding lactic acid and ethanol under anaerobic conditions are shown as well. The overall reactions of gluconeogenesis and the functional significance of this pathway are presented. The experimental treatment involved the presentation of this hypermedia for Nutrition undergraduate students (UFSC as a tool for better comprehension of the theme. The students revealed that it was extremely effective in promoting the understanding of the enzymatic mechanisms involved in glycolysis. This suggests that there is a significant added value in employing the software as an instructional effort to enhance student’s abilities to understand biochemical pathways.

  17. 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...... young subjects. In a second experiment magnetic resonance spectroscopy ((1)H-MRS) was performed after exhaustive exercise to assess lactate levels in the brain (n = 5). Exercise increased the AV(O2) from 3.2 +/- 0.1 at rest to 3.5 +/- 0.2 mM (mean +/-s.e.m.; P ...-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...

  18. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine Miyama Hospital (Japan)); Doi, C. (Tohoku Univ. School of Literature (Japan). Dept. of Psychology); Yamaguchi, T.; Sasaki, H. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine); Matsui, H.; Yamada, K. (Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Kinomura, S. (Miyama Hospital (Japan) Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Itoh, M. (Tohoku Univ. School of Medicine (Japan). Cyclotron Radioisotope Center)

    1991-08-01

    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 {sup 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.).

  19. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    International Nuclear Information System (INIS)

    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.)

  20. Fructose modifies the hormonal response and modulates lipid metabolism in aerobic exercise after glucose supplementation

    OpenAIRE

    Fernández, Juan Marcelo; Da Silva-Grigoletto, Marzo Edir; Ruano-Ruiz, Juan; Caballero-Villarraso, Javier; Moreno-Luna, Rafael; Tunez-Fiñana, Isaac; Tasset-Cuevas, Inmaculada; Pérez-Martinez, Pablo; López-Miranda, José; Pérez-Jiménez, Francisco

    2008-01-01

    Abstract The metabolic response, when aerobic exercise is performed after the ingestion of glucose plus fructose, is unclear. To compare the hormonal and lipid responses provoked by the ingestion of glucose plus fructose in relation to glucose alone, during aerobic exercise and the recovery phase, we administered two beverages containing glucose plus fructose or glucose in a randomised crossover design, to twenty healthy, aerobically trained volunteers. After a 15-minute resting pe...

  1. 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.

  2. Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans

    Science.gov (United States)

    Objective: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during carbohydrate ingestion suggest that glucose may regulate HT signaling but are potentially confoun...

  3. Exercise, Energy Intake, Glucose Homeostasis, and the Brain

    OpenAIRE

    Van Praag, Henriette; Fleshner, Monika; Schwartz, Michael W.; Mattson, Mark P.

    2014-01-01

    Here we summarize topics covered in an SFN symposium that considered how and why exercise and energy intake affect neuroplasticity and, conversely, how the brain regulates peripheral energy metabolism. This article is not a comprehensive review of the subject, but rather a view of how the authors' findings fit into a broader context. Emerging findings elucidate cellular and molecular mechanisms by which exercise and energy intake modify the plasticity of neural circuits in ways that affect br...

  4. Metabolic and mitogenic transduction cascades in skeletal muscle : Implications for exercise effects on glucose metabolism and gene regulation

    OpenAIRE

    Yu, Mei

    2003-01-01

    Level of physical activity is linked to improved glucose homeostasis. The molecular signaling mechanisms by which insulin and exercise/muscle contractions lead to increased glucose transport and metabolism and gene expression have not been completely elucidated. The overall aim of this thesis was to identify novel regulatory mechanisms governing exercisesensitive signaling pathways to glucose metabolism and gene transcription in skeletal muscle. Components of the insulin (IR...

  5. Role of brain glutamic acid metabolism changes in neurodegenerative pathologies

    OpenAIRE

    Nina Pavlovna Kanunnikova

    2012-01-01

    Glutamic acid is an essential participant of brain metabolism. It is known that the glutamate is a neurotransmitter in a numerous part of the brain synapses and acts through various ionotropic or metabotropic receptors. Multiple alterations of the brain glutamate system are observed in both acute and chronic brain injures. Glutamate metabolism changes take place in many neurodegenerative pathologies, such as brain ischemia, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, amyot...

  6. Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

    OpenAIRE

    Warringa, R.A.J.; Hoeben, R C; Koper, W.J.; Sykes, J.E.C.; Golde, L.M.G. van; Lopes-Cardozo, M.

    1987-01-01

    Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated the effects of hydrocortisone on the development of oligodendrocytes, on the activities of oligodendrocyte-specific enzymes and on glucose- and lipid-metabolism of the glial cells. (1) Hydrocortis...

  7. Interaction Between the Central and Peripheral Effects of Insulin in Controlling Hepatic Glucose Metabolism in the Conscious Dog

    OpenAIRE

    Ramnanan, Christopher J.; Kraft, Guillaume; Smith, Marta S.; Farmer, Ben; Neal, Doss; Williams, Phillip E.; Lautz, Margaret; Farmer, Tiffany; Donahue, E. Patrick; Cherrington, Alan D.; Edgerton, Dale S.

    2012-01-01

    The importance of hypothalamic insulin action to the regulation of hepatic glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is unknown. Thus, we assessed the role of central insulin action in the response of the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic clamp, hepatic portal vein insulin delivery was increased three- or eightfold in the conscious dog. Insulin action was studied in the presence or absence of intracerebroventricularl...

  8. Sirtuins: from Metabolic Regulation to Brain Aging

    Directory of Open Access Journals (Sweden)

    Wenzhen eDuan

    2013-07-01

    Full Text Available Brain aging is characterized by progressive loss of neurophysiological functions that is often accompanied by age-associated neurodegeneration. Calorie restriction has been linked to extension of lifespan and reduction of the risk of neurodegenerative diseases in experimental model systems. Several signaling pathways have been indicated to underlie the beneficial effects of calorie restriction, among which the sirtuin family has been suggested to play a central role. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Sirtuins represent a promising new class of conserved deacetylases that play an important role in regulating metabolism and aging. This review focuses on current understanding of the relation between metabolic pathways involving sirtuins and the brain aging process, with focus on SIRT1 and SIRT3. Identification of therapeutic agents capable of modulating the expression and/or activity of sirtuins is expected to provide promising strategies for ameliorating neurodegeneration. Future investigations regarding the concerted interplay of the different sirtuins will help us understand more about the aging process, and potentially lead to the development of therapeutic approaches for the treatment of age-related neurodegenerative diseases and promotion of successful aging.

  9. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals.

    Science.gov (United States)

    Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

    2015-12-15

    Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary clocks in the brain and peripheral organs. The SCN control peripheral timing via the autonomic and neuroendocrine system, as well as via behavioral outputs. The sleep-wake cycle, the feeding/fasting rhythm and most hormonal rhythms, including that of leptin, ghrelin and glucocorticoids, usually show an opposite phase (relative to the light-dark cycle) in diurnal and nocturnal species. By contrast, the SCN clock is most active at the same astronomical times in these two categories of mammals. Moreover, in both species, pineal melatonin is secreted only at night. In this review we describe the current knowledge on the regulation of glucose and lipid metabolism by central and peripheral clock mechanisms. Most experimental knowledge comes from studies in nocturnal laboratory rodents. Nevertheless, we will also mention some relevant findings in diurnal mammals, including humans. It will become clear that as a consequence of the tight connections between the circadian clock system and energy metabolism, circadian clock impairments (e.g., mutations or knock-out of clock genes) and circadian clock misalignments (such as during shift work and chronic jet-lag) have an adverse effect on energy metabolism, that may trigger or enhancing obese and diabetic symptoms. PMID:25662277

  10. Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Beck, T.; Krieglstein, J.

    1987-03-01

    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/sub 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 (/sup 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.

  11. Comparison of cerebral metabolism of glucose in normal human and cancer patients

    International Nuclear Information System (INIS)

    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

  12. Acute Modulation of Sugar Transport in Brain Capillary Endothelial Cell Cultures during Activation of the Metabolic Stress Pathway*

    OpenAIRE

    Cura, Anthony J.; Carruthers, Anthony

    2010-01-01

    GLUT1-catalyzed equilibrative sugar transport across the mammalian blood-brain barrier is stimulated during acute and chronic metabolic stress; however, the mechanism of acute transport regulation is unknown. We have examined acute sugar transport regulation in the murine brain microvasculature endothelial cell line bEnd.3. Acute cellular metabolic stress was induced by glucose depletion, by potassium cyanide, or by carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which reduce or deplete i...

  13. Alterations in local cerebral glucose metabolism and endogenous thyrotropin-releasing hormone levels in rolling mouse Nagoya and effect of thyrotropin-releasing hormone tartrate.

    Science.gov (United States)

    Nakayama, T; Nagai, Y

    1996-11-01

    To identify the brain region(s) responsible for the expression of ataxic gaits in an ataxic mutant mouse model, Rolling mouse Nagoya (RMN), changes in local cerebral glucose metabolism in various brain regions and the effect of thyrotropin-releasing hormone tartrate (TRH-T), together with alterations in endogenous thyrotropin-releasing hormone (TRH) levels in the brains of RMN, were investigated. Ataxic mice [RMN (rol/rol)] showed significant decreases in glucose metabolism in regions of the diencephalon: thalamic dorsomedial nucleus, lateral geniculate body and superior colliculus; brain stem: substantia nigra, raphe nucleus and vestibular nucleus; and cerebellar nucleus as compared with normal controls [RMN (+/+)]. When RMN (rol/rol) was treated with TRH-T (10 mg/kg, equivalent to 7 mg/kg free TRH), glucose metabolism was significantly increased in these regions. These results suggest that these regions may be responsible for ataxia. We also found that TRH levels in the cerebellum and brain stem of RMN (rol/rol) were significantly higher than those of RMN (+/+). These results suggest that ataxic symptoms in RMN (rol/rol) may relate to the abnormal metabolism of TRH and energy metabolism in the cerebellum and/or brain stem and that exogenously given TRH normalizes them.

  14. Evaluation of mild hypothermia therapy for neonatal hypoxic-ischaemic encephalopathy on brain energy metabolism using 18F-fluorodeoxyglucose positron emission computed tomography

    OpenAIRE

    Luo, Mei; Li, Qingping; DONG, WENBIN; Zhai, Xuesong; Kang, Lan

    2014-01-01

    It remains unclear whether mild hypothermia affects energy metabolism in the brain tissue of newborns with hypoxic-ischaemic encephalopathy (HIE). The current study aimed to investigate the effect of mild hypothermia on energy metabolism in neonatal HIE and assess brain energy metabolism using position emission tomography/computed tomography (PET/CT) scanning. The mean standardised uptake values of 18F-fluorodeoxyglucose (18F-FDG) were used to determine the glucose metabolic rate in various b...

  15. 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.

  16. Simultaneous measurement of blood flow and glucose metabolism by autoradiographic techniques

    International Nuclear Information System (INIS)

    A double tracer autoradiographic technique using 131I-iodo-antipyrine and 14C-deoxyglucose is presented for the simultaneous measurement of blood flow and cerebral glucose utilization in the same animal. 131I is a gamma emitting isotope with a half life of 8.06 days and can be detected with adequate resolution on standard autoradiographic films. Autoradiograms are made before and after decay of 131I; the time interval between the 2 exposures and the concentration of the 2 tracers is adjusted to avoid significant cross-contamination. In this way, 2 film exposures are obtained which can be processed quantitatively like single tracer autoradiograms. The validity of the method for the investigation of local coupling of flow and metabolism was tested under various physiological and pathophysiological conditions. Coupling was tight in barbiturate-anesthetized healthy animals, but not under halothane anesthesia where uncoupling occurred in various subcortical structures. Focal seizures induced by topical application of penicillin on the cortical surface led to a coupled increase of metabolism and flow in thalamic relay nuclei but not at the site of penicillin administration where increased glucose utilization was not accompanied by similar increase in blood flow. Both coupled and uncoupled increases in local glucose utilization were observed in spreading depression and in circumscribed areas of experimental brain tumors. The results obtained demonstrate that double tracer autoradiography allows allows the very precise local assessment of cerebral blood flow and glucose utilization, and, therefore, is particularly suited to the study of regional coupling processes under various experimental conditions

  17. EFFECT OF ACUPUNCTURE STIMULATION AT SANYINJIAO (SP 6) ON CEREBRAL GLUCOSE METABOLISM IN DYSMENORRHEA PATIENTS

    Institute of Scientific and Technical Information of China (English)

    GONG Ping; ZHANG Ming-min; JIANG Li-ming; WU Zhi-jian; WANG Wei; HUANG Guang-ying

    2006-01-01

    Objective: To study the central mechanism of acupuncture stimulation of Sanyinjiao ( 三阴交 SP6) in relieving dysmenorrhea. Methods: A total of 6 dysmenorrhea volunteer patients were subjected into this study. On the first positron emission tomography (PET) scan examination, they were assigned to pseudoacupuncture group by using the acupuncture needle just to prick the skin of Sanyinjiao (SP 6); while on the second PET scans, they were assigned to acupuncture group by inserting the needle into the same acupoint.18F fluorodeoxyglucose (18F-FDG) PET of the whole brain was performed during pseudo-acupuncture and real acupuncture of Sanyinjiao (SP 6). The acquired PET data were analyzed by using statistical parametric mapping (SPM) software to determine changes of glucose metabolism in different cerebral regions. The patient's pain intensity was rated by using 0- 10 numerical pain intensity scale. Results: After pseudo-acupuncture stimulation of Sanyinjiao (SP 6), no significant changes were found in the pain intensity ( P >0.05), while after real-acupuncture stimulation, the pain intensity declined significantly (P < 0.01 ). Following acupuncture of the right Sanyinjiao (SP 6), multiple cerebral regions involving pain were activated (increase of glucose metabolism), including ipsilateral lenticular nucleus (globus pallidus, putamen), ipsilateral cerebellum and insular lobe, bilateral dorsal thalamus, ipsilateral paracentral lobule, bilateral amygdaloid bodies, contralateral substantia nigra of the midbrain, bilateral second somatosensory (S Ⅱ ) areas, ispsilateral hippocampal gyrus, frontal part of the ipsilateral cingulated gyrus, and bilateral mammary bodies of the hypothalamus. In addition, fewer regions of the cerebral cortex responded with decrease of the glucose metabolism after real acupuncture.

  18. Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple System Atrophy

    Directory of Open Access Journals (Sweden)

    Kyum-Yil Kwon

    2009-05-01

    Full Text Available Background: To investigate the relationship between presenting clinical manifestations and imaging features of multisystem neuronal dysfunction in MSA patients, using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET. Methods: We studied 50 consecutive MSA patients with characteristic brain MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P and 16 with early MSA-cerebellar (MSA-C. The cerebral glucose metabolism of all MSA patients was evaluated in comparison with 25 age-matched controls. 18F-FDG PET results were assessed by the Statistic Parametric Mapping (SPM analysis and the regions of interest (ROI method. Results: The mean time from disease onset to 18F-FDG PET was 25.9±13.0 months in 34 MSA-P patients and 20.1±11.1 months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater decrease in possible MSA-P than in probable MSA-P (p=0.031. Although the Unified Multiple System Atrophy Rating Scale (UMSARS score did not differ between possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04 and bradykinesia (p= 0.008 were significantly higher in possible MSA-P than in probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of the cerebellum than probable MSA-C (p=0.016. Conclusions: Our results may suggest that the early neuropathological pattern of possible MSA with a predilection for the striatonigral or olivopontocerebellar system differs from that of probable MSA, which has prominent involvement of the autonomic nervous system in addition to the striatonigral or olivopontocerebellar system.

  19. 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.

  20. The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

    International Nuclear Information System (INIS)

    The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with 18F-Dopa and 18F-FDG respectively. The 18F-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 18F-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 18F-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 18F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of 18F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the 18F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author)

  1. Quantitative on-line monitoring of cellular glucose and lactate metabolism in vitro with slow perfusion

    NARCIS (Netherlands)

    Leegsma-Vogt, G; Venema, K; Brouwer, N; Gramsbergen, JB; Copray, S; Korf, J

    2004-01-01

    An on-line in vitro perfusion technique is described that allows the continuous quantification of cellular glucose metabolism in vitro. Using biosensor technology, we measure glucose and lactate metabolism at a minute-to-minute time resolution for periods up to several days. The application of our p

  2. Voxel based statistical analysis method for microPET studies to assess the cerebral glucose metabolism in cat deafness model: comparison to ROI based method

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Lee, Jae Sung; Park, Min Hyun; Lee, Jong Jin; Kang, Hye Jin; Lee, Hyo Jeong; Oh, Seung Ha; Kim, Chong Sun; Jung, June Key; Lee, Myung Chul; Lee, Dong Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lim, Sang Moo [KIRAMS, Seoul (Korea, Republic of)

    2005-07-01

    Imaging research on the brain of sensory-deprived cats using small animal PET scanner has gained interest since the abundant information about the sensory system of ths animal is available and close examination of the brain is possible due to larger size of its brain than mouse or rat. In this study, we have established the procedures for 3D voxel-based statistical analysis (SPM) of FDG PET image of cat brain, and confirmed using ROI based-method. FDG PET scans of 4 normal and 4 deaf cats were acquired for 30 minutes using microPET R4 scanner. Only the brain cortices were extracted using a masking and threshold method to facilitate spatial normalization. After spatial normalization and smoothing, 3D voxel-wise and ROI based t-test were performed to identify the regions with significant different FDG uptake between the normal and deaf cats. In ROI analysis, 26 ROIs were drawn on both hemispheres, and regional mean pixel value in each ROI was normalized to the global mean of the brain. Cat brains were spatially normalized well onto the target brain due to the removal of background activity. When cerebral glucose metabolism of deaf cats were compared to the normal controls after removing the effects of the global count, the glucose metabolism in the auditory cortex, head of caudate nucleus, and thalamus in both hemispheres of the deaf cats was significantly lower than that of the controls (P<0.01). No area showed a significantly increased metabolism in the deaf cats even in higher significance level (P<0.05). ROI analysis also showed significant reduction of glucose metabolism in the same region. This study established and confirmed a method for voxel-based analysis of animal PET data of cat brain, which showed high localization accuracy and specificity and was useful for examining the cerebral glucose metabolism in a cat cortical deafness model.

  3. Brain glycogen – new perspectives on its metabolic function and regulation at the subcellular level

    Directory of Open Access Journals (Sweden)

    Linea Frimodt Obel

    2012-03-01

    Full Text Available Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g. liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies – it is a highly dynamic molecule with versatile implications in brain function, i.e. synaptic activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms underlying glycogen metabolism. Based on i the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP, ii alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and iii a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g. turnover is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology.

  4. Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones

    Science.gov (United States)

    Pichette, Jennifer

    2016-01-01

    Diabetes and its comorbidities continue to be a major health problem worldwide. Understanding the precise mechanisms that control glucose homeostasis and their dysregulation during diabetes are a major research focus. Hydrogen sulfide (H2S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose. Of importance, H2S production and signaling in these tissues are altered during both type 1 and type 2 diabetes mellitus. This review first examines how H2S is produced both endogenously and by gastrointestinal microbes, with a particular focus on the altered production that occurs during obesity and diabetes. Next, the action of H2S on the metabolic organs with key roles in glucose homeostasis, with a particular focus on insulin, is described. Recent work has also suggested that the effects of H2S on glucose homeostasis goes beyond its role in insulin secretion. Several studies have demonstrated important roles for H2S in hepatic glucose output and adipose glucose uptake. The mechanism of H2S action on these metabolic organs is described. In the final part of this review, future directions examining the roles of H2S in other metabolic and glucoregulatory hormone secreting tissues are proposed. PMID:27478532

  5. Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder

    International Nuclear Information System (INIS)

    Patients with generalized anxiety disorder (n = 18) entered a 21-day, double-blind, placebo-controlled random assignment trial of clorazepate. Positron emission tomography with 18F-deoxyglucose was carried out before and after treatment. Decreases in glucose metabolic rate in visual cortex and relative increases in the basal ganglia and thalamus were found. A correlation between regional changes in metabolic rate and regional benzodiazepine receptor binding density from other human autopsy studies was observed; brain regions highest in receptor density showed the greatest decrease in rate

  6. Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder

    Energy Technology Data Exchange (ETDEWEB)

    Buchsbaum, M.S.; Wu, J.; Haier, R.; Hazlett, E.; Ball, R.; Katz, M.; Sokolski, K.; Lagunas-Solar, M.; Langer, D.

    1987-06-22

    Patients with generalized anxiety disorder (n = 18) entered a 21-day, double-blind, placebo-controlled random assignment trial of clorazepate. Positron emission tomography with YF-deoxyglucose was carried out before and after treatment. Decreases in glucose metabolic rate in visual cortex and relative increases in the basal ganglia and thalamus were found. A correlation between regional changes in metabolic rate and regional benzodiazepine receptor binding density from other human autopsy studies was observed; brain regions highest in receptor density showed the greatest decrease in rate.

  7. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

    OpenAIRE

    SONG, KUI; Li, Min; Xu, Xiaojun; Xuan, Li; HUANG, GUINIAN; Liu, Qifa

    2016-01-01

    Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug-resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose tra...

  8. Hepatocyte Growth Factor Is a Novel Stimulator of Glucose Uptake and Metabolism in Skeletal Muscle Cells*

    OpenAIRE

    Perdomo, German; Martinez-Brocca, Maria A.; Bhatt, Bankim A.; Brown, Nicholas F.; O'Doherty, Robert M.; Garcia-Ocaña, Adolfo

    2008-01-01

    Skeletal muscle plays a major role in glucose and lipid metabolism. Active hepatocyte growth factor (HGF) is present in the extracellular matrix in skeletal muscle. However, the effects of HGF on glucose and lipid metabolism in skeletal muscle are completely unknown. We therefore examined the effects of HGF on deoxyglucose uptake (DOGU), glucose utilization, and fatty acid oxidation (FAO) in skeletal muscle cells. HGF significantly enhanced DOGU in mouse soleus muscles in vitro. Furthermore, ...

  9. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice

    OpenAIRE

    Janet eGuo; Vikas eBakshi; Ai-Ling eLin

    2015-01-01

    Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with eithe...

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

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    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.

  11. Voxel-based statistical analysis of regional cerebral glucose metabolism in children with attention-deficit hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    Ji-Hoon Kim; Young-In Chung; Jung Sub Lee; In-Joo Kim; Yong-Ki Kim; Seong-Jang Kim

    2011-01-01

    The technique of region of interest-based positron emission tomography is limited by its poor reliability and relatively few examined brain regions. In the present study, we compared brain metabolism assessed using fluorine-18-fluorodeoxyglucose positron emission tomography between 14 attention-deficit hyperactivity disorder (ADHD) patients and 15 normal controls with scoliosis at resting state by statistical parametric mapping. Glucose metabolism was decreased in the left parahippocampal gyrus, left hippocampus, left anterior cingulate gyrus, right anterior and posterior lobes of the cerebellum, left superior temporal gyrus, left insula, left medial and middle frontal gyri, right medial frontal gyrus, and left basal ganglia (putamen, amygdala, and caudate nucleus) in children with ADHD. These data suggest that children with ADHD exhibit hypometabolism in various brain regions compared to controls, indicating that ADHD symptoms are unlikely the result of abnormalities in specific areas.

  12. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    International Nuclear Information System (INIS)

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect

  13. Regional difference of glucose metabolism reduction in equivocal Alzheimer's disease and elderly depressed patients

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the difference in cerebral glucose metabolism between patients with equivocal Alzheimer's disease (eAD) and those with elderly major depression (DEP). 31 patients with eAD, 7 patients with DEP, and 15 age matched normal controls were scanned with FDG-PET. Each FDG-PET images was normalized to the cerebellar activity before voxel-voxel analysis using SPM99. In comparison with normal controls, the eAD patents showed the most significant reduction of glucose metabolism (hypometabolism) in anterior inferior temporal gyrus in left, followed by bilateral posterior cingulate, left thalamus, and inferior parietal lobe. Patients with DEP showed hypometabolism in precuneus, inferior and middle frontal gyri in left, and right angular gyrus. Significantly lower activity was found in left inferior temporal gyrus in DEP in comparison to the eAD. Patients with eAD and DEP showed different pattern of hypometabolism, especially in inferior temporal gyrus. FDG brain PET may be useful in differential diagnosis between equivocal Alzheimer's disease and elderly depression

  14. Altered brain arginine metabolism in schizophrenia

    Science.gov (United States)

    Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

    2016-01-01

    Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease. PMID:27529679

  15. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    Science.gov (United States)

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  16. Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

    Science.gov (United States)

    Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

    2016-07-01

    Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. PMID:27207544

  17. Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction

    NARCIS (Netherlands)

    van Straten, Esther M. E.; Bloks, Vincent W.; van Dijk, Theo H.; Baller, Julius F. W.; Huijkman, Nicolette C. A.; Kuipers, Irma; Verkade, Henkjan J.; Plosch, Torsten

    2012-01-01

    Background: Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome. Objective: We aim

  18. Continuous and simultaneous electrochemical measurements of glucose, lactate, and ascorbate in rat brain following brain ischemia.

    Science.gov (United States)

    Lin, Yuqing; Yu, Ping; Hao, Jie; Wang, Yuexiang; Ohsaka, Takeo; Mao, Lanqun

    2014-04-15

    Developing new tools and technologies to enable recording the dynamic changes of multiple neurochemicals is the essence of better understanding of the molecular basis of brain functions. This study demonstrates a microfluidic chip-based online electrochemical system (OECS) for in vivo continuous and simultaneous monitoring of glucose, lactate, and ascorbate in rat brain. To fabricate the microfluidic chip-based detecting system, a microfluidic chip with patterned channel is developed into an electrochemical flow cell by incorporating the chip with three surface-modified indium-tin oxide (ITO) electrodes as working electrodes, a Ag/AgCl wire as reference electrode, and a stainless steel tube as counter electrode. Selective detection of ascorbate is achieved by the use of single-walled carbon nanotubes (SWNTs) to largely facilitate the electrochemical oxidation of ascorbate, while a dehydrogenase-based biosensing mechanism with methylene green (MG) adsorbed onto SWNTs as an electrocatalyst for the oxidation of dihydronicotiamide adenine dinucleotide (NADH) is employed for biosensing of glucose and lactate. To avoid the crosstalk among three sensors, the sensor alignment is carefully designed with the SWNT-modified electrode in the upstream channel and paralleled glucose and lactate biosensors in the downstream channels. With the microfluidic chip-based electrochemical flow cell as the detector, an OECS is successfully established by directly integrating the microfluidic chip-based electrochemical flow cell with in vivo microdialysis. The OECS exhibits a good linear response toward glucose, lactate, and ascorbate with less crosstalk. This property, along with the high stability and selectivity, enables the OECS for continuously monitoring three species in rat brain following brain ischemia. PMID:24621127

  19. Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study.

    Directory of Open Access Journals (Sweden)

    Mark Lambie

    Full Text Available Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism.We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients, with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis.The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004 and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003 in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006 in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6-10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34.In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses.

  20. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning.

    Science.gov (United States)

    Linnman, Clas; Zeidan, Mohamed A; Pitman, Roger K; Milad, Mohammed R

    2012-02-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning. PMID:22207247

  1. Resveratrol supplementation does not improve metabolic function in non-obese women with normal glucose tolerance

    OpenAIRE

    Yoshino, Jun; Conte, Caterina; Fontana, Luigi; Mittendorfer, Bettina; Imai, Shin-ichiro; Kenneth B Schechtman; Gu, Charles; Kunz, Iris; Fanelli, Filippo Rossi; Patterson, Bruce W.; Klein, Samuel

    2012-01-01

    Resveratrol has been reported to improve metabolic function in metabolically-abnormal rodents and humans, but has not been studied in non-obese people with normal glucose tolerance. We conducted a randomized, double-blind, placebo-controlled trial to evaluate the metabolic effects of 12 weeks of resveratrol supplementation (75 mg/day) in non-obese, postmenopausal women with normal glucose tolerance. Although resveratrol supplementation increased plasma resveratrol concentration, it did not ch...

  2. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F

    2016-07-01

    Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain

  3. Endothelial dysfunction in normal and abnormal glucose metabolism.

    Science.gov (United States)

    Esper, Ricardo J; Vilariño, Jorge O; Machado, Rogelio A; Paragano, Antonio

    2008-01-01

    independent risk factors for coronary heart disease, stroke, and peripheral arterial disease. Hyperglycemia causes glycosylation of proteins and phospholipids, thus increasing intracellular oxidative stress. Nonenzymatic reactive products, glucose-derived Schiff base, and Amadori products form chemically reversible early glycosylation products which subsequently rearrange to form more stable products, some of them long-lived proteins (collagen) which continue undergoing complex series of chemical rearrangements to form advanced glycosylation end products (AGEs). Once formed, AGEs are stable and virtually irreversible. AGEs generate ROS with consequent increased vessel oxidative damage and atherogenesis. The impressive correlation between coronary artery disease and alterations in glucose metabolism has raised the hypothesis that atherosclerosis and diabetes may share common antecedents. Large-vessel atherosclerosis can precede the development of diabetes, suggesting that rather than atherosclerosis being a complication of diabetes, both conditions may share genetic and environmental antecedents, a 'common soil'. PMID:18230954

  4. Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy.

    Directory of Open Access Journals (Sweden)

    Brenda eBartnik-Olson

    2013-10-01

    Full Text Available The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI and the use of 13C labeled substrates and nuclear magnetic resonance (NMR spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle.

  5. [Relationships of glucose transporter 4 with cognitive changes induced by high fat diet and glucose metabolism in hippocampus].

    Science.gov (United States)

    Zhang, Yun-Li; Wang, Lin

    2016-06-25

    The hippocampus not only plays a role in appetite and energy balance, but also is particularly important in learning and memory. Figuring out the relationships of hippocampal glucose transporter 4 (GLUT4) with hippocampal glucose metabolism and hippocampus-dependent cognitive function is very important to clearly understand the pathophysiological basis of nutritional obesity and diabetes-related diseases, and treat obesity and cognitive dysfunction. Therefore, this study reviewed recent researches conducted on hippocampal GLUT4, hippocampal glucose metabolism, and hippocampus-dependent cognitive function. In this review, we mainly discussed: (1) The structure of GLUT4 and the distribution and function of GLUT4 in the hippocampus; (2) The translocation of GLUT4 in the hippocampus; (3) The relationships of the PI3K-Akt-GLUT4 signaling pathway with the high fat diet-induced changes of cognitive function and the glucose metabolism in the hippocampus; (4) The associations of the PI3K-Akt-GLUT4 signaling pathway with the diabetes-related cognitive dysfunction in the hippocampus; (5) The potential mechanisms of cognitive dysfunction induced by glucose metabolic disorder. PMID:27350206

  6. The relationship between fasting serum glucose and cerebral glucose metabolism in late-life depression and normal aging

    Science.gov (United States)

    Marano, Christopher M.; Workman, Clifford I.; Lyman, Christopher H.; Kramer, Elisse; Hermann, Carol R.; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David; Smith, Gwenn S.

    2015-01-01

    Evidence exists for late-life depression (LLD) as both a prodrome of and risk factor for Alzheimer’s disease (AD). The underlying neurobiological mechanisms are poorly understood. Impaired peripheral glucose metabolism may explain the association between depression and AD given the connection between type 2 diabetes mellitus with both depression and AD. Positron emission tomography (PET) measures of cerebral glucose metabolism are sensitive to detecting changes in neural circuitry in LLD and AD. Fasting serum glucose (FSG) in non-diabetic young (YC; n=20) and elderly controls (EC; n=12) and LLD patients (n=16) was correlated with PET scans of cerebral glucose metabolism on a voxel-wise basis. The negative correlations were more extensive in EC versus YC and in LLD patients versus EC. Increased FSG correlated with decreased cerebral glucose metabolism in LLD patients to a greater extent than in EC in heteromodal association cortices involved in mood symptoms and cognitive deficits observed in LLD and dementia. Negative correlations in YC were observed in sensory and motor regions. Understanding the neurobiological consequences of diabetes and associated conditions will have substantial public health significance given that this is a modifiable risk factor for which prevention strategies could have an important impact on lowering dementia risk. PMID:24650451

  7. Regional cerebral metabolic rate for glucose and cerebrospinal fluid monoamine metabolites in subacute sclerosing panencephalitis

    International Nuclear Information System (INIS)

    Regional cerebral metabolic rate for glucose (rCMRglu) and cerebrospinal fluid monoamine metabolites were measured in two cases of subacute sclerosing panencephalitis (SSPE) with different clinical courses. A marked decrease in rCMRglu was found in the cortical gray matter of a patient with rapidly developing SSPE (3.6 - 4.2 mg/100 g brain tissue/min). However, the rCMRglu was preserved in the caudate and lenticular nuclei of the patient (7.7 mg/100 g/min). The rCMRglu in a patient with slowly developing SSPE revealed patterns and values similar to those of the control. Cerebrospinal fluid monoamine metabolites ; homovanilic acid and 5-hydroxyindoleacetic acid, were decreased in both rapidly and slowly developing SSPE. These data indicated that rCMRglu correlated better with the neurological and psychological status and that dopaminergic and serotonergic abnormalities have been implicated in pathophysiology of SSPE. (author)

  8. 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

    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...... stress indicators returned to baseline values. Activation-induced resetting of the cerebral oxygen/glucose uptake ratio is not necessarily accounted for by increased lactate production from nonoxidative glucose metabolism....

  9. Drosophila adiponectin receptor in insulin producing cells regulates glucose and lipid metabolism by controlling insulin secretion.

    Directory of Open Access Journals (Sweden)

    Su-Jin Kwak

    Full Text Available Adipokines secreted from adipose tissue are key regulators of metabolism in animals. Adiponectin, one of the adipokines, modulates pancreatic beta cell function to maintain energy homeostasis. Recently, significant conservation between Drosophila melanogaster and mammalian metabolism has been discovered. Drosophila insulin like peptides (Dilps regulate energy metabolism similarly to mammalian insulin. However, in Drosophila, the regulatory mechanism of insulin producing cells (IPCs by adipokine signaling is largely unknown. Here, we describe the discovery of the Drosophila adiponectin receptor and its function in IPCs. Drosophila adiponectin receptor (dAdipoR has high homology with the human adiponectin receptor 1. The dAdipoR antibody staining revealed that dAdipoR was expressed in IPCs of larval and adult brains. IPC- specific dAdipoR inhibition (Dilp2>dAdipoR-Ri showed the increased sugar level in the hemolymph and the elevated triglyceride level in whole body. Dilps mRNA levels in the Dilp2>dAdipoR-Ri flies were similar with those of controls. However, in the Dilp2>dAdipoR-Ri flies, Dilp2 protein was accumulated in IPCs, the level of circulating Dilp2 was decreased, and insulin signaling was reduced in the fat body. In ex vivo fly brain culture with the human adiponectin, Dilp2 was secreted from IPCs. These results indicate that adiponectin receptor in insulin producing cells regulates insulin secretion and controls glucose and lipid metabolism in Drosophila melanogaster. This study demonstrates a new adipokine signaling in Drosophila and provides insights for the mammalian adiponectin receptor function in pancreatic beta cells, which could be useful for therapeutic application.

  10. The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer's disease

    International Nuclear Information System (INIS)

    The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer's disease (AD) patients and healthy elderly controls. Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [11C]PIB to assess amyloid-β plaque load and [18F]FDG to assess glucose metabolism. [11C]PIB binding and [18F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho = 0.56, p 11C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [18F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration. (orig.)

  11. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti;

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  12. Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure

    Energy Technology Data Exchange (ETDEWEB)

    Nishizawa, Sadahiko; Ueno, Makoto; Shimono, Taro; Toyoda, Hiroshi; Konishi, Junji [Kyoto Univ. (Japan). Graduate School of Medicine; Kuwabara, Hiroto

    2001-06-01

    [{sup 18}F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3{+-}0.2 and 5.0{+-}0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p<0.05). Although no systematic deviations were noted in K{sup *}{sub 1} or rCMRglc, there were small deviations in K{sup *} (less than 10%) and LC (less than 5%) with a statistical significance (p<0.01). The deviation between the measurements in K{sup *} and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constrains can be used to estimate rCMRglc and LC sequentially in a single PET scanning session. (author)

  13. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

    Science.gov (United States)

    Geurts, L; Neyrinck, A M; Delzenne, N M; Knauf, C; Cani, P D

    2014-03-01

    Crosstalk between organs is crucial for controlling numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Several pathological conditions, such as obesity and type 2 diabetes, are characterised by a loss of or excessive inter-organ communication that contributes to the development of disease. Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis). Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance. Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia. Recently, we hypothesised that specific metabolic dysregulations occurring at the level of numerous organs (e.g. gut, adipose tissue, muscles, liver and brain) rely from gut microbiota modifications. In this review, we discuss the mechanisms linking gut permeability, adipose tissue metabolism, and glucose homeostasis, and recent findings that show interactions between the gut microbiota, the endocannabinoid system and the apelinergic system. These specific systems are discussed in the context of the gut-to-peripheral organ axis (intestine, adipose tissue and brain) and impacts on metabolic regulation. In the present review, we also briefly describe the impact of a variety of non-digestible nutrients (i.e. inulin-type fructans, arabinoxylans, chitin glucans and polyphenols). Their effects on the composition of the gut microbiota and

  14. Increased insulin sensitivity and responsiveness of glucose metabolism in adipocytes from female versus male rats.

    OpenAIRE

    Guerre-Millo, M.; Leturque, A.; Girard, J.; Lavau, M

    1985-01-01

    This study was undertaken to examine whether there were sex-associated differences in the action of insulin on glucose metabolism in adipocytes. Insulin binding and the dose-response curves for glucose transport (assessed by measuring the cell-associated radioactivity after 15-s incubation with 50 microM [6-14C]glucose) and [U-14C]glucose (5 mM) metabolism into CO2 and lipids were compared in retroperitoneal adipocytes from age-matched (84 d) male and female rats. In addition, the activity of...

  15. Evaluation of glucose metabolic abnormality in postlingually deaf patients using F-18-FDG positron emission tomography and statistical parametric mapping

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Lee, Dong Soo; Oh, Seung Ha; Kim, Chong Sun; Park, Kwang Suk; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2000-07-01

    We have previously reported the prognostic relevance of cross-modal cortical plasticity in prelingual deaf patients revealed by F-18-FDG PET and SPM analysis. In this study, we investigated metabolic abnormality in postlingual deaf patients, whose clinical features are different from prelingual deafness. Nine postlingual deaf patients (age: 30.5 {+-}14.0) were performed on F-18-FDG brain PET. We compared their PET images with those of age-matched 20 normal controls (age: 27.1 {+-}8.6), and performed correlation analysis to investigate the relationship between glucose metabolism and deaf duration using SPM99. Glucose metabolism of deaf patients was significantly (p<0.05, corrected) decreased in both anterior cingulate, inferior frontal cortices, and superior temporal cortices, and left hippocampus. Metabolism in both superior temporal cortices and association area in inferior parietal cortices showed significant (p<0.01, uncorrected) positive correlation with deaf duration. Decreased metabolism in hippocampus accompanied with hypometabolism in auditory related areas can be explained by recent finding of anatomical connectivity between them, and may be the evidence indicating their functional connectivity. Metabolism recovery in auditory cortex after long deaf duration suggests that cortical plasticity takes place also in postlingual deafness.

  16. Investigations on the effects of ''Ecstasy'' on cerebral glucose metabolism: an 18-FDG PET study

    International Nuclear Information System (INIS)

    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<0.05) and right prefrontal superior (-4.6%, p<0.05). On the other hand, rMRGlu was significantly increased in the bilateral cerebellum (right: +10.1%, p<0.05; left: +7.6%, p<0.05) and in the right putamen (+6.2%, p<0.05). Conclusions: The present study revealed acute neurometabolic changes under the 'Ecstasy' analogon MDE indicating a fronto-striato-cerebellar dysbalance with parallels to other psychotropic substances and various endogenous psychoses respectively. (orig.)

  17. Metabolic Imaging of Breast Cancer and the Normal Brain

    DEFF Research Database (Denmark)

    Asghar Butt, Sadia

    biological systems - breast cancer and normal brain. Breast cancer metabolism was longitudinally monitored in a mouse model using MRS of hyperpolirized pyruvate. The results demonstrated that we could monitor the changes in metabolism with increasing disease severity. The normal cerebral metabolism of α......-ketoisocaproate (KIC) was studied in the rat brain. The findings showed that hyperpolarized KIC is a promising substrate for in vivo evaluation of specific enzymatic activity....

  18. Brain Morphometric Correlates of Metabolic Variables in HIV: The CHARTER Study

    Science.gov (United States)

    ARCHIBALD, S.L.; MCCUTCHAN, J.A.; SANDERS, C.; WOLFSON, T.; JERNIGAN, T.L.; ELLIS, R.J.; ANCES, B.M.; COLLIER, A.C.; MCARTHUR, J.C.; MORGELLO, S.; SIMPSON, D.M.; MARRA, C.; GELMAN, B.B.; CLIFFORD, D.B.; GRANT, I.; FENNEMA-NOTESTINE, C.

    2014-01-01

    Objectives: Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multi-site CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort. Design: Cross-sectional study of 222 HIV-infected individuals. Methods: Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Results: Greater body mass index (BMI) was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Conclusions: Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction. PMID:25227933

  19. Role of SUMO-specific protease 2 in reprogramming cellular glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Shuang Tang

    Full Text Available Most cancer cells exhibit a shift in glucose metabolic strategy, displaying increased glycolysis even with adequate oxygen supply. SUMO-specific proteases (SENPs de-SUMOylate substrates including HIF1α and p53,two key regulators in cancer glucose metabolism, to regulate their activity, stability and subcellular localization. However, the role of SENPs in tumor glucose metabolism remains unclear. Here we report that SUMO-specific protease 2 (SENP2 negatively regulates aerobic glycolysis in MCF7 and MEF cells. Over-expression of SENP2 reduces the glucose uptake and lactate production, increasing the cellular ATP levels in MCF7 cells, while SENP2 knockout MEF cells show increased glucose uptake and lactate production along with the decreased ATP levels. Consistently, the MCF7 cells over-expressing SENP2 exhibit decreased expression levels of key glycolytic enzymes and an increased rate of glucose oxidation compared with control MCF7 cells, indicating inhibited glycolysis but enhanced oxidative mitochondrial respiration. Moreover, SENP2 over-expressing MCF7 cells demonstrated a reduced amount of phosphorylated AKT, whereas SENP2 knockout MEFs exhibit increased levels of phosphorylated AKT. Furthermore, inhibiting AKT phosphorylation by LY294002 rescued the phenotype induced by SENP2 deficiency in MEFs. In conclusion, SENP2 represses glycolysis and shifts glucose metabolic strategy, in part through inhibition of AKT phosphorylation. Our study reveals a novel function of SENP2 in regulating glucose metabolism.

  20. Early Metabolic Crisis-Related Brain Atrophy and Cognition in Traumatic Brain Injury

    OpenAIRE

    Wright, Matthew J.; McArthur, David L.; Alger, Jeffry R.; Van Horn, Jack; Irimia, Andrei; Filippou, Maria; Glenn, Thomas C.; Hovda, David A.; Vespa, Paul

    2013-01-01

    Traumatic brain injury often results in acute metabolic crisis. We recently demonstrated that this is associated with chronic brain atrophy, which is most prominent in the frontal and temporal lobes. Interestingly, the neuropsychological profile of traumatic brain injury is often characterized as ‘frontal-temporal’ in nature, suggesting a possible link between acute metabolic crisis related-brain atrophy and neurocognitive impairment in this population. While focal lesions and diffuse axonal ...

  1. Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells.

    Science.gov (United States)

    Amaral, Ana I; Hadera, Mussie G; Tavares, Joana M; Kotter, Mark R N; Sonnewald, Ursula

    2016-01-01

    Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have, therefore, characterized metabolic functions of primary oligodendrocyte precursor cell cultures at late stages of differentiation using isotope-labelled metabolites. We report that differentiated oligodendrocyte lineage cells avidly metabolize glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2-(13)C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolized via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1-(13)C]lactate or [1,2-(13)C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2-(13)C]acetate, we show that oligodendrocytes convert acetate into acetyl CoA which is metabolized in the tricarboxylic acid cycle. Analysis of labelling patterns of alanine after incubation of cells with [1,2-(13)C]acetate and [1,2-(13)C]glucose showed catabolic oxidation of malate or oxaloacetate. In conclusion, we report that oligodendrocyte lineage cells at late differentiation stages are metabolically highly active cells that are likely to contribute considerably to the metabolic activity of the CNS. PMID:26352325

  2. Clinical observation of glucose metabolism disorders in elderly patients with obstructive sleep apnea disorder

    Institute of Scientific and Technical Information of China (English)

    张蔷

    2013-01-01

    Objective To explore the correlation between obstructive sleep apnea hypoventilation syndrome (OSAHS) and glucose metabolism disorders in patients without diabetes mellitus.Methods A total of 88 patients with OSAHS but without diabetes mellitus from 2009 to 2011 in

  3. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    Directory of Open Access Journals (Sweden)

    Shengxi Meng

    2013-01-01

    Full Text Available Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA, one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism.

  4. Influence of tacrolimus on glucose metabolism before and after renal transplantation : a prospective study

    NARCIS (Netherlands)

    Duijnhoven, E M; Boots, J M; Christiaans, M H; Wolffenbuttel, B H; Van Hooff, J P

    2001-01-01

    Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the

  5. Low and high dietary protein:carbohydrate ratios during pregnancy affect materno-fetal glucose metabolism in pigs.

    Science.gov (United States)

    Metges, Cornelia C; Görs, Solvig; Lang, Iris S; Hammon, Harald M; Brüssow, Klaus-Peter; Weitzel, Joachim M; Nürnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried

    2014-02-01

    Inadequate dietary protein during pregnancy causes intrauterine growth retardation. Whether this is related to altered maternal and fetal glucose metabolism was examined in pregnant sows comparing a high-protein:low-carbohydrate diet (HP-LC; 30% protein, 39% carbohydrates) with a moderately low-protein:high-carbohydrate diet (LP-HC; 6.5% protein, 68% carbohydrates) and the isoenergetic standard diet (ST; 12.1% protein, 60% carbohydrates). During late pregnancy, maternal and umbilical glucose metabolism and fetal hepatic mRNA expression of gluconeogenic enzymes were examined. During an i.v. glucose tolerance test (IVGTT), the LP-HC-fed sows had lower insulin concentrations and area under the curve (AUC), and higher glucose:insulin ratios than the ST- and the HP-LC-fed sows (P < 0.05). Insulin sensitivity and glucose clearance were higher in the LP-HC sows compared with ST sows (P < 0.05). Glucagon concentrations during postabsorptive conditions and IVGTT, and glucose AUC during IVGTT, were higher in the HP-LC group compared with the other groups (P < 0.001). (13)C glucose oxidation was lower in the HP-LC sows than in the ST and LP-HC sows (P < 0.05). The HP-LC fetuses were lighter and had a higher brain:liver ratio than the ST group (P < 0.05). The umbilical arterial inositol concentration was greater in the HP-LC group (P < 0.05) and overall small fetuses (230-572 g) had higher values than medium and heavy fetuses (≥573 g) (P < 0.05). Placental lactate release was lower in the LP-HC group than in the ST group (P < 0.05). Fetal glucose extraction tended to be lower in the LP-HC group than in the ST group (P = 0.07). In the HP-LC and LP-HC fetuses, hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC) was higher than in the ST fetuses (P < 0.05). In conclusion, the HP-LC and LP-HC sows adapted by reducing glucose turnover and oxidation and having higher glucose utilization, respectively. The HP-LC and LP

  6. Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus Macaques

    OpenAIRE

    Adams, Sean H.; Stanhope, Kimber L.; Grant, Ryan W.; Cummings, Bethany P.; Havel, Peter J.

    2008-01-01

    Diurnal patterns of circulating leptin concentrations are attenuated after consumption of fructose-sweetened beverages compared with glucose-sweetened beverages, likely a result of limited postprandial glucose and insulin excursions after fructose. Differences in postprandial exposure of adipose tissue to peripheral circulating fructose and glucose or in adipocyte metabolism of the two sugars may also be involved. Thus, we compared plasma leptin concentrations after 6-h iv infusions of saline...

  7. Resting brain metabolic correlates of neuroticism and extraversion in young men.

    Science.gov (United States)

    Kim, Sang Hee; Hwang, Ji Hee; Park, Hyun Soo; Kim, Sang Eun

    2008-05-28

    Neuroticism and extraversion are two core dimensions of personality and are considered to be associated with emotional disorders. We investigated resting state brain metabolic correlates of neuroticism and extraversion using a positron emission tomography. Twenty healthy young men completed an F-flurodeoxyglucose-PET scan at rest and the Korean version of the revised Eysenck Personality Questionnaire. Neuroticism was negatively correlated with regional glucose metabolism in prefrontal regions including the medial prefrontal cortex. Extraversion was positively correlated with metabolism in the right putamen. These results suggest close associations between resting state brain activity in the prefrontal and striatal regions and specific personality traits and thus contribute to the understanding of the neurobiological bases of predisposition to psychiatric disorders.

  8. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    International Nuclear Information System (INIS)

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either [1-14C] glucose or [6-14C] glucose resulted in significant decreases in CO2 production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats

  9. Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle

    OpenAIRE

    Chao, Lily C.; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F.

    2007-01-01

    Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared to oxidativ...

  10. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs

    Science.gov (United States)

    Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

    2016-01-01

    Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; Pstarch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics. PMID:27583555

  11. Metabolic inflexibility is a common feature of impaired fasting glycaemia and impaired glucose tolerance.

    Science.gov (United States)

    Færch, Kristine; Vaag, Allan

    2011-12-01

    Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation. Impaired metabolic flexibility is related to insulin resistance and type 2 diabetes, but whether metabolic flexibility is impaired in individuals with the pre-diabetic states isolated impaired fasting glycaemia (i-IFG) and isolated impaired glucose tolerance (i-IGT) is unknown. Using the gold standard euglycaemic hyperinsulinaemic clamp technique combined with indirect calorimetry, we measured peripheral insulin sensitivity, lipid and glucose oxidation, and thus metabolic flexibility in 66 individuals with normal glucose tolerance (NGT, n = 20), i-IFG (n = 18) and i-IGT (n = 28). During insulin stimulation, individuals with i-IGT displayed reduced insulin sensitivity including reduced glucose oxidation. Interestingly, those with i-IFG exhibited reduced glucose oxidation and a slightly elevated lipid oxidation rate during insulin infusion despite having normal total peripheral glucose disposal. Thus, metabolic flexibility was significantly reduced in individuals with both i-IFG and i-IGT even after adjustment for BMI and insulin sensitivity. The data indicate that metabolic inflexibility may precede the development of overt peripheral insulin resistance in pre-diabetic individuals. However, prospective studies are needed to confirm this notion. PMID:21207234

  12. Enhanced muscle glucose metabolism after exercise in the rat

    DEFF Research Database (Denmark)

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

    1984-01-01

    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...... was evident. The data suggest that the restoration of muscle glycogen after exercise occurs in two phases. In phase I, muscle glycogen is depleted and insulin-stimulated glucose utilization and glucose utilization in the absence of added insulin may both be enhanced. In phase II glycogen levels have returned...

  13. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Swedo, S.E.; Schapiro, M.B.; Grady, C.L.; Cheslow, D.L.; Leonard, H.L.; Kumar, A.; Friedland, R.; Rapoport, S.I.; Rapoport, J.L.

    1989-06-01

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

  14. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

    International Nuclear Information System (INIS)

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system

  15. Depressed glucose consumption at reperfusion following brain ischemia does not correlate with mitochondrial dysfunction and development of infarction: an in vivo positron emission tomography study.

    Science.gov (United States)

    Martín, Abraham; Rojas, Santiago; Pareto, Deborah; Santalucia, Tomàs; Millán, Olga; Abasolo, Ibane; Gómez, Vanessa; Llop, Jordi; Gispert, Joan D; Falcon, Carles; Bargalló, Núria; Planas, Anna M

    2009-05-01

    Glucose consumption is severely depressed in the ischemic core, whereas it is maintained or even increased in penumbral regions during ischemia. Conversely, glucose utilization is severely reduced early after reperfusion in spite that glucose and oxygen are available. Experimental studies suggest that glucose hypometabolism might be an early predictor of brain infarction. However, the relationship between early glucose hypometabolism with later development of infarction remains to be further studied in the same subjects. Here, glucose consumption was assessed in vivo by positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) in a rat model of ischemia/reperfusion. Perfusion was evaluated by PET with (13)NH(3) during and after 2-hour (h) middle cerebral artery occlusion, and (18)F-FDG was given after 2h of reperfusion. Brain infarction was evaluated at 24h. Mitochondrial oxygen consumption was examined ex vivo using a biochemical method. Cortical (18)F-FDG uptake was reduced by 45% and 25% in the ischemic core and periphery, respectively. However, substantial alteration of mitochondrial respiration was not apparent until 24h, suggesting that mitochondria retained the ability to consume oxygen early after reperfusion. These results show reduced glucose use at early reperfusion in regions that will later develop infarction and, to a lesser extent, in adjacent regions. Depressed glucose metabolism in the ischemic core might be attributable to reduced metabolic requirement due to irreversible cellular injury. However, reduced glucose metabolism in peripheral regions suggests either an impairment of glycolysis or reduced glucose demand. Thus, our study supports that glycolytic depression early after reperfusion is not always related to subsequent development of infarction.

  16. Visual and SPM analysis of regional cerebral glucose metabolism in adult patients with neurofibromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Joon Kee; An, Young Sil; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University, School of Medicine, Suwon (Korea, Republic of)

    2005-07-01

    We evaluated the regional cerebral glucose metabolism in adult patients with neurofibromatosis (NF) using visual and SPM analysis, and compared with MRI findings. A total of 11 adult patients with NF type I were prospectively included in the study. All patients underwent F-18 FDG PET and brain MRI within 2 month of each other. All hypometabolic areas on PET were determined visually by 2 nuclear medicine physician and compared with MRI findings. SPM analysis was done using 42 normal controls with p = 0.005. Seven of 11 PET images showed 10 hypometabolic areas and 4 of 11 MRIs showed 6 areas of signal change brain parenchyma. Hypometabolic areas were bilateral thalamus (n=5), left temporal cortex (n=4) and dentate nucleus (n=1). In only 2 lesions (thalamus and dentate nucleus), hypometabolic foci were consistently related to signal change on MRI. SPM analysis revealed significantly decreased area in bilateral thalamus and left temporal cortex. F-18 FDG PET revealed significant hypometabolism in bilateral thalamus and left temporal cortex in adult patients with NF, and it might be helpful in understanding developmental abnormality of NF.

  17. Combination of temozolomide and Taxol exerts a synergistic inhibitory effect on Taxol‑resistant glioma cells via inhibition of glucose metabolism.

    Science.gov (United States)

    Guan, Ding-Guo; Chen, Han-Min; Liao, Sheng-Fang; Zhao, Tian-Zhi

    2015-11-01

    Malignant gliomas, which comprise the most common type of primary malignant brain tumor, are associated with a poor prognosis and quality of life. Paclitaxel (Taxol) and temozolomide (TMZ) are Food and Drug Administration‑approved anticancer agents, which are known to have therapeutic applications in various malignancies. However, similar to other chemotherapeutic agents, the development of resistance to TMZ and Taxol is common. The aim of the present study was to investigate the regulation of glucose metabolism by TMZ and Taxol in glioma cells. The results demonstrated that glioma cells exhibit decreased glucose uptake and lactate production in response to treatment with TMZ; however, glucose metabolism was increased in response to Taxol treatment. Following analysis of TMZ‑ and Taxol‑resistant cell lines, it was reported that glucose metabolism was decreased in the TMZ‑resistant cells, but was increased in the Taxol‑resistant cells. Notably, a combination of TMZ and Taxol exerted synergistic inhibitory effects on Taxol‑resistant glioma cells. However, the synergistic phenotype was not observed following treatment with a combination of 5‑fluorouracil and Taxol. Furthermore, restoration of glucose metabolism by overexpression of glucose transporter 1 in Taxol‑resistant cells resulted in regained resistance to Taxol. Therefore, the present study proposes a novel mechanism accounting for the synergistic effects of Taxol and TMZ co‑treatment, which may contribute to the development of therapeutic strategies for overcoming chemoresistance in patients with cancer.

  18. Novel aspects of brain metabolism as revealed by magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Full text: The techniques of Magnetic Resonance Spectroscopy (MRS) and Imaging (MRI) are outlined, and compared with Positron Emission Tomography (PET). Invasive PET techniques using 19F-fluorodeoxyglucose (FDG) and 18O2 form the main basis of brain activation studies, and with 19F-fluoroDOPA, make major contributions to studies on neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease. However the technique has no chemical specificity so can provide no knowledge of intermediary metabolism. Non-invasive MRI is also being applied to brain activation studies but also has no chemical specificity. On the other hand MRS has superb chemical specificity, although it suffers from low sensitivity. A most interesting example of this is the use of 13C-MRS. If glucose is labelled on the no. 1 or no. 2 positions with 13C, the passage of the label through different neuronal and glial metabolic pathways can be followed. If acetate is similarly labelled, metabolic routes through specifically glial pathways can be monitored, since acetate is taken up only by glia. These studies contributed to knowledge on metabolic trafficking, in that glia produce alanine, citrate and lactate in addition to the previously characterised production of glutamine. Studies on the hypoxic brain revealed increased production of alanine, lactate and glycerol 3-phosphate, providing further understanding of the role of the NADH redox state. 'Isotopomer analysis' of 13C resonances provides more information on metabolic pathways, because the chemical shift of a 13C atom is specifically affected by a neighbouring 13C within the same molecule. This approach was used to demonstrate that neurotransmitter γ-aminobutyrate (GABA) is partly derived from glial glutamine. Analogous 13C MRS studies are now providing novel information on metabolic flux rates within the human brain, and the most exciting developments are to follow changes in these rates on brain activation which can be

  19. JNK1 Deficiency Does Not Enhance Muscle Glucose Metabolism in Lean Mice*

    OpenAIRE

    Witczak, CA; Hirshman, MF; Jessen, N.; Fujii, N; Seifert, M.; Brandauer, J; Hotamisligil, GS; Goodyear, LJ

    2006-01-01

    Mice deficient in c‐jun‐NH2‐terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity‐induced insulin resistance, suggesting increased glucose disposal into skeletal muscle. Thus, we assessed whether JNK1 deficiency enhances muscle glucose metabolism. Ex vivo insulin or contraction‐induced muscle [³H]‐2‐deoxyglucose uptake was not altered in JNK1 knockout mice, demonstrating that JNK1 does not regulate blood glucose levels via direct a...

  20. Abnormal glucose metabolism in acute myocardial infarction: influence on left ventricular function and prognosis

    DEFF Research Database (Denmark)

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E;

    2009-01-01

    to be particularly attributable to an increased incidence of post-infarction congestive heart failure. A relationship between glucose metabolism and LV function could potentially explain this excess mortality. METHODS: In patients without known diabetes, glucose metabolism was determined using an oral glucose...... atrial volume index) and by measuring plasma N-terminal pro-B-type natriuretic peptide levels. RESULTS: After adjustment for age and gender, a linear relationship between the degree of abnormal glucose metabolism was observed for each marker of LV dysfunction (p(trend) ... atrial volume index (p = 0.10). During a median follow-up of 21 months, 32 patients died, and 39 patients met the secondary end point of death or hospitalization for heart failure. After adjustment for differences in LV function, as well as other relevant characteristics, newly detected, as well as known...

  1. Metabolic Syndrome, Brain Magnetic Resonance Imaging, and Cognition

    OpenAIRE

    Cavalieri, Margherita; Ropele, Stefan; Petrovic, Katja; Pluta-Fuerst, Aga; Homayoon, Nina; Enzinger, Christian; Grazer, Anja; Katschnig, Petra; Schwingenschuh, Petra; Berghold, Andrea; Schmidt, Reinhold

    2010-01-01

    OBJECTIVE We explored cognitive impairment in metabolic syndrome in relation to brain magnetic resonance imaging (MRI) findings. RESEARCH DESIGN AND METHODS We studied 819 participants free of clinical stroke and dementia of the population-based Austrian Stroke Prevention Study who had undergone brain MRI, neuropsychological testing, and a risk factor assessment relevant to National Cholesterol Education Program Adult Treatment Panel III criteria–defined metabolic syndrome. High-sensitivity C...

  2. Muscle glucose metabolism following exercise in the rat

    DEFF Research Database (Denmark)

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

    1982-01-01

    Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during...... perfusion of their isolated hindquarters. Glucose utilization by the hindquarter was the same in exercised and control rats perfused in the absence of added insulin; however, when insulin (30-40,000 muU/ml) was added to the perfusate, glucose utilization was greater after exercise. Prior exercise lowered...... both, the concentration of insulin that half-maximally stimulated glucose utilization (exercise, 150 muU/ml; control, 480 muU/ml) and modestly increased its maximum effect. The increase in insulin sensitivity persisted for 4 h following exercise, but was not present after 24 h. The rate-limiting step...

  3. Ethanol, not metabolized in brain, significantly reduces brain metabolism, probably via specific GABA(A) receptors

    Science.gov (United States)

    Rae, Caroline D.; Davidson, Joanne E.; Maher, Anthony D.; Rowlands, Benjamin D.; Kashem, Mohammed A.; Nasrallah, Fatima A.; Rallapalli, Sundari K.; Cook, James M; Balcar, Vladimir J.

    2014-01-01

    Ethanol is a known neuromodulatory agent with reported actions at a range of neurotransmitter receptors. Here, we used an indirect approach, measuring the effect of alcohol on metabolism of [3-13C]pyruvate in the adult Guinea pig brain cortical tissue slice and comparing the outcomes to those from a library of ligands active in the GABAergic system as well as studying the metabolic fate of [1,2-13C]ethanol. Ethanol (10, 30 and 60 mM) significantly reduced metabolic flux into all measured isotopomers and reduced all metabolic pool sizes. The metabolic profiles of these three concentrations of ethanol were similar and clustered with that of the α4β3δ positive allosteric modulator DS2 (4-Chloro-N-[2-(2-thienyl)imidazo[1,2a]-pyridin-3-yl]benzamide). Ethanol at a very low concentration (0.1 mM) produced a metabolic profile which clustered with those from inhibitors of GABA uptake, and ligands showing affinity for α5, and to a lesser extent, α1-containing GABA(A)R. There was no measureable metabolism of [1,2-13C]ethanol with no significant incorporation of 13C from [1,2-13C]ethanol into any measured metabolite above natural abundance, although there were measurable effects on total metabolite sizes similar to those seen with unlabeled ethanol. The reduction in metabolism seen in the presence of ethanol is therefore likely to be due to its actions at neurotransmitter receptors, particularly α4β3δ receptors, and not because ethanol is substituting as a substrate or because of the effects of ethanol catabolites acetaldehyde or acetate. We suggest that the stimulatory effects of very low concentrations of ethanol are due to release of GABA via GAT1 and the subsequent interaction of this GABA with local α5-containing, and to a lesser extent, α1-containing GABA(A)R. PMID:24313287

  4. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    Energy Technology Data Exchange (ETDEWEB)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana [IRCCS Neuromed, Neurogenetics Unit and Centre for Rare Disease, Pozzilli (Italy); Romanelli, Pantaleo [IRCCS Neuromed, Department of Neurosurgery, Pozzilli (Italy); Giovacchini, Giampiero; Ciarmiello, Andrea [S. Andrea Hospital, Unit of Nuclear Medicine, La Spezia (Italy); Frati, Luigi [University ' ' Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Mansi, Luigi [Second University of Naples, Department of Nuclear Medicine, Naples (Italy)

    2009-07-15

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and {sup 18}F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  5. Reflections on the application of 13C-MRS to research on brain metabolism.

    Science.gov (United States)

    Morris, Peter; Bachelard, Herman

    2003-01-01

    The power of (13)C-MRS lies in its unique chemical specificity, enabling detection and quantification of metabolic intermediates which would not be so readily monitored using conventional radiochemical techniques. Examples from animal studies, by examination of tissue extracts from the whole brain, brain slices and cultured cells, include observation of intermediates such as citrate and triose phosphates which have yielded novel information on neuronal/glial relationships. The use of (13)C-labelled acetate as a specific precursor for glial metabolism provided evidence in support of the view that some of the GABA produced in the brain is derived from glial glutamine. Such studies have also provided direct evidence on the contribution of anaplerotic pathways to intermediary metabolism. Analogous studies are now being performed on the human brain, where (13)C-acetate is used to quantitate the overall contribution of glial cells to intermediary metabolism, and use of (13)C-glucose enables direct calculation of rates of flux through the TCA (F(TCA)) and of the glutamate-glutamine cycle (F(CYC)), leading to the conclusion that the rate of glial recycling of glutamate accounts for some 50% of F(TCA). The rate of 0.74 micromol min(-1) g(-1) for F(TCA) is compatible with PET rates of CMRglc of 0.3-0.4 micromol min(-1) g(-1) (since each glucose molecule yields two molecules of pyruvate entering the TCA). Our brain activation studies showed a 60% increase in F(TCA), which is very similar to the increases in CBF and in CMRglc observed in PET activation studies.

  6. Glucose metabolism in mammalian cell culture: new insights for tweaking vintage pathways.

    Science.gov (United States)

    Mulukutla, Bhanu Chandra; Khan, Salmaan; Lange, Alex; Hu, Wei-Shou

    2010-09-01

    Cultured mammalian cells are major vehicles for producing therapeutic proteins, and energy metabolism in those cells profoundly affects process productivity. The characteristic high glucose consumption and lactate production of industrial cell lines as well as their adverse effects on productivity have been the target of both cell line and process improvement for several decades. Recent research advances have shed new light on regulation of glucose metabolism and its links to cell proliferation. This review highlights our current understanding in this area of crucial importance in bioprocessing and further discusses strategies for harnessing new findings toward process enhancement through the manipulation of cellular energy metabolism.

  7. PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent

    Energy Technology Data Exchange (ETDEWEB)

    Tamminga, C.A.; Tanimoto, K.; Kuo, S.; Chase, T.N.; Contreras, P.C.; Rice, K.C.; Jackson, A.E.; O' Donohue, T.L.

    1987-01-01

    The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with (/sup 14/C)-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.

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

    Energy Technology Data Exchange (ETDEWEB)

    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 /sup 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.

  9. Influence of blood glucose on the expression of glucose transporter proteins 1 and 3 in the brain of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    HOU Wei-kai; FU Chun-li; ZHANG Wen-wen; CHEN Li; XIAN Yu-xin; ZHANG Li; LAI Hong; HOU Xin-guo; XU Yu-xin; YU Ting; XU Fu-yu; SONG Jun

    2007-01-01

    Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier (BBB), which is mediated by the facilitative glucose transporter protein 1 (GLUT1), and then across the neural cell membranes, which is mediated by GLUT3. This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in a rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy.Methods Diabetes mellitus was induced with streptozotocin (STZ) in 30 rats. The rats were randomly divided into 3 groups: diabetic group without blood glucose control (group DM1), diabetic rats treated with low dose insulin (group DM2),and diabetic rats treated with high dose insulin (group DM3). The mRNA and protein levels of GLUT1 and GLUT3 were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively.Results Compared with normal control rats, the GLUT1 mRNA was reduced by 46.08%, 29.80%, 19.22% (P<0.01) in DM1, DM2, and DM3 group, respectively; and the GLUT3 mRNA was reduced by 75.00%, 46.75%, and 17.89% (P<0.01)in DM1, DM2, and DM3 group, respectively. The abundance of GLUT1 and GLUT3 proteins had negative correlation with the blood glucose level (P<0.01). The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats.Conclusions Chronic hyperglycemia downregulates GLUT1 and GLUT3 expression at both mRNA and protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downregulation of GLUT1 and GLUT3 expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.

  10. Program for PET image alignment: Effects on calculated differences in cerebral metabolic rates for glucose

    International Nuclear Information System (INIS)

    A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double-blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states

  11. Typical Cerebral Metabolic Patterns in Neurodegenerative Brain Diseases

    NARCIS (Netherlands)

    Teune, Laura K.; Bartels, Anna L.; de Jong, Bauke M.; Willemsen, Antoon T. M.; Eshuis, Silvia A.; de Vries, Jeroen J.; van Oostrom, Joost C. H.; Leenders, Klaus L.

    2010-01-01

    The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [F-18]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting t

  12. Compartmentalised cerebral metabolism of [1,6-13C]glucose determined by in vivo 13C NMR spectroscopy at 14.1 T

    Directory of Open Access Journals (Sweden)

    João M.N. Duarte

    2011-06-01

    Full Text Available Cerebral metabolism is compartmentalised between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by 13C NMR spectroscopy upon infusion of 13C-enriched compounds, especially glucose. Rats under light α-chloralose anaesthesia were infused with [1,6-13C]glucose and 13C enrichment in the brain metabolites was measured by 13C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining 13C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%. We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (VTCA and neurotransmission rate (VNT were 0.45±0.01 and 0.11±0.01 µmol/g/min, respectively. Glial VTCA was found to be for 38±3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (VPC was 0.069±0.004 µmol/g/min, i.e. 25±1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.

  13. Demographic and metabolic characteristics of individuals with progressive glucose tolerance

    Directory of Open Access Journals (Sweden)

    A.L. Mendes

    2009-03-01

    Full Text Available We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT, insulin secretion (first and second phases and insulin sensitivity indices (from hyperglycemic clamp assay for both groups. In the normal glucose tolerant phase, progressors presented: 1 a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2 a reduced first-phase insulin secretion (2.0 ± 0.3 vs 2.3 ± 0.3 pmol/L; P < 0.02 with a similar insulin sensitivity index and a lower disposition index (3.9 ± 0.2 vs 4.1 ± 0.2 µmol·kg-1·min-1 ; P < 0.05 vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05 and reduced early insulin response to OGTT (progressors, 1st: 2.10 ± 0.34 vs 2nd: 1.87 ± 0.25 pmol/mmol; non-progressors, 1st: 2.15 ± 0.28 vs 2nd: 2.03 ± 0.39 pmol/mmol; P < 0.05. Theses data suggest that β-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

  14. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp

    2012-01-01

    Uncoupling Protein 2 (UCP2) is expressed in the pancreatic β-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for...... UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression...... was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase...

  15. Islet glucose metabolism and insulin release in two animal models of glucose intolerance

    OpenAIRE

    Ling, Zong-Chao

    1999-01-01

    Type 2 diabetes is a complex and heterogenous disease resulting from the interaction of defects of both genetic and environmental origin. Abnormalities contributing to the pathogenesis of type 2 diabetes include impaired [beta]-cell function, peripheral insulin resistance and increased hepatic glucose production. In the present study we have mainly used two animal models of glucose intolerance, i.e., spontaneously diabetic GK rats and transgenic mice with overexpressed gluco...

  16. Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients

    DEFF Research Database (Denmark)

    Sonne, David P; Hare, Kristine J; Martens, Pernille;

    2013-01-01

    Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We...... examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat......-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum...

  17. 脑深部电刺激对帕金森病患者基底节环路的影响及其作用机制%The Effect of Deep Brain Stimulation(DBS) on Resting- state Cerebral Glucose Metabolism of Advanced Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    赵永波; 李殿友; 孙伯民; 王乔树

    2003-01-01

    目的研究双侧丘脑底核(STN)慢性电刺激术(DBS)对晚期帕金森病(PD)患者静止期脑局部糖代谢的影响,并探讨DBS的作用机制.方法对7例进行双侧STNDBS的晚期PD患者,在术前和术后1个月电刺激条件下,分别进行18F-脱氧葡萄糖(FDG)/PET检查和UPDRS评分,并通过SPM99统计学软件进行数据分析,研究双侧STNDBS对PD患者脑内代谢的影响.结果双侧STN DBS使PD患者临床症状明显改善,同时脑局部糖代谢也发生了明显变化:双侧豆状核、脑干(中脑、脑桥)、双侧顶枕部、运动前区(BA6)及扣带回的脑代谢增加;前额叶底部、海马的脑代谢减少(P<0.05).结论双侧STN DBS可能通过兴奋STN轴突的方式,使轴突投射区域的基底节上行和下行通路代谢改善,并增加相应的额叶高级运动中枢的代谢,使PD患者临床症状改善.%Objective To study the effects of bilateral subthalamic nucleus (STN) stimulation onresting-state cerebral glucose metabolism of advanced Parkinson's disease, and investigate the mecha-nism of deep brain stimulation (DBS). Methods Seven consecutive advanced Parkinson' s diseasepatients (4 men, 3 women; mean age 64±4; mean H-Y disability scale 4.4±0. 65) with bilateral STNDBS underwent 2 times 18F-FDG/PET examinations at rest preoperatively and one month postopera-tively with STN stimulation on respectively. The unified Parkinson' s disease rating scale was used toevaluate the clinical state under each condition. Statistical parametric mapping (SPM) was used to inves-tigate regional cerebral metabolic rate of glucose (rCMRGlu) during STN stimulation in comparison withr CMRGlu preoperatively. Results STN stimulation improved the clinical symptoms obviously for eachpatient. The significant increase of rCMRGlu was found in bilateral lentiform nucleus, brainstem (mid-brain and pon), bilateral premotor area (BA6), parietal-occipital cortex and anterior cingulated cortex,and the marked decrease of it was

  18. Glucose metabolism in gamma-irradiated rice seeds

    International Nuclear Information System (INIS)

    Gamma-irradiation of 30 kR in rice seeds caused marked inhibition in seedling growth, and prevented the release of reduced sugar during the period of 25 to 76hr after soaking. The C6/C1 ratio following irradiation continued to decrease up to the 76th hour of soaking; the control's ratio tended to increase with comparable soaking time. The percentage recovery of 14C in carbon dioxide from glucose -1-14C was lower in irradiated than in control seeds. These results indicate that gamma-irradiation reduces the participation of the pentose phosphate pathway in glucose catabolism during an early period of germination. (author)

  19. Effect of glucocorticoid therapy upon glucose metabolism in COPD patients with acute exacerbation

    International Nuclear Information System (INIS)

    Objective: To study the effect of glucocorticoids therapy upon glucose metabolism in COPD patients with acute exacerbation. Methods: Plasma glucose and insulin levels in COPD patients after intravenous administration of 10 mg dexamethasone daily for 5 days were determined oral with glucose tolerance test (OGTT) and insulin release test (IRT). Results: 1) The levels of basal plasma glucose and insulin were significantly higher in severe hypoxemic group than those in moderate hypoxemic group (p 2 (r = -0.5242, p < 0.05). 2) The levels of plasma glucose in intermediate and severe hypoxemic groups were remarkable higher (p < 0.05) than those in mild group. The two peak times of glucose curve were observed at one and two hour after oral glucose load. 3) After the administration of glucocorticoids, at half an hour and one hour plasma glucose levels were significantly higher than those before, the peak time of glucose levels appeared earlier and the insulin release levels were higher than they were before therapy (p < 0.05). Conclusion: COPD patients with acute exacerbation complicated with hypoxemia had problems of impaired glucose tolerance. The administration of glucocorticoids made the impairment worse

  20. Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes.

    Directory of Open Access Journals (Sweden)

    Dallas R Donohoe

    Full Text Available A prodigious number of microbes inhabit the human body, especially in the lumen of the gastrointestinal (GI tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metabolism, we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germfree and conventionally-raised C57BL/6 mice. These experiments demonstrated that microbiota are required for energy homeostasis in the proximal colon to a greater extent than other segments of the GI tract that also harbor high densities of bacteria. This tissue-specific effect is consistent with colonocytes utilizing bacterially-produced butyrate as their primary energy source, whereas most other cell types utilize glucose. However, it was surprising that glucose did not compensate for butyrate deficiency. We measured a 3.5-fold increase in glucose uptake in germfree colonocytes. However, (13C-glucose metabolic-flux experiments and biochemical assays demonstrated that they shifted their glucose metabolism away from mitochondrial oxidation/CO(2 production and toward increased glycolysis/lactate production, which does not yield enough ATPs to compensate. The mechanism responsible for this metabolic shift is diminished pyruvate dehydrogenase (PDH levels and activity. Consistent with perturbed PDH function, the addition of butyrate, but not glucose, to germfree colonocytes ex vivo stimulated oxidative metabolism. As a result of this energetic defect, germfree colonocytes exhibited a partial block in the G(1-to-S-phase transition that was rescued by a butyrate-fortified diet. These data reveal a mechanism by which microbiota regulate glucose utilization to influence energy homeostasis and cell-cycle progression of mammalian host cells.

  1. Inborn errors of metabolism: a cause of abnormal brain development.

    Science.gov (United States)

    Nissenkorn, A; Michelson, M; Ben-Zeev, B; Lerman-Sagie, T

    2001-05-22

    Brain malformations are caused by a disruption in the sequence of normal development by various environmental or genetic factors. By modifying the intrauterine milieu, inborn errors of metabolism may cause brain dysgenesis. However, this association is typically described in single case reports. The authors review the relationship between brain dysgenesis and specific inborn errors of metabolism. Peroxisomal disorders and fatty acid oxidation defects can produce migration defects. Pyruvate dehydrogenase deficiency, nonketotic hyperglycinemia, and maternal phenylketonuria preferentially cause a dysgenetic corpus callosum. Abnormal metabolism of folic acid causes neural tube defects, whereas defects in cholesterol metabolism may produce holoprosencephaly. Various mechanisms have been proposed to explain abnormal brain development in inborn errors of metabolism: production of a toxic or energy-deficient intrauterine milieu, modification of the content and function of membranes, or disturbance of the normal expression of intrauterine genes responsible for morphogenesis. The recognition of a metabolic disorder as the cause of the brain malformation has implications for both the care of the patient and for genetic counseling to prevent recurrence in subsequent pregnancies. PMID:11383558

  2. A low-protein diet during pregnancy alters glucose metabolism and insulin secretion.

    Science.gov (United States)

    Souza, Denise de Fátima I; Ignácio-Souza, Letícia M; Reis, Sílvia Regina de L; Reis, Marise Auxiliadora de B; Stoppiglia, Luiz Fabrizio; Carneiro, Everardo Magalhães; Boschero, Antonio Carlos; Arantes, Vanessa Cristina; Latorraca, Márcia Queiroz

    2012-03-01

    In pancreatic islets, glucose metabolism is a key process for insulin secretion, and pregnancy requires an increase in insulin secretion to compensate for the typical insulin resistance at the end of this period. Because a low-protein diet decreases insulin secretion, this type of diet could impair glucose homeostasis, leading to gestational diabetes. In pancreatic islets, we investigated GLUT2, glucokinase and hexokinase expression patterns as well as glucose uptake, utilization and oxidation rates. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. The insulin secretion in 2.8 mmol l(-1) of glucose was higher in islets from LPP rats than that in islets from CP, CNP and LPNP rats. Maximal insulin release was obtained at 8.3 and 16.7 mmol l(-1) of glucose in LPP and CP groups, respectively. The glucose dose-response curve from LPNP group was shifted to the right in relation to the CNP group. In the CP group, the concentration-response curve to glucose was shifted to the left compared with the CNP group. The LPP groups exhibited an "inverted U-shape" dose-response curve. The alterations in the GLUT2, glucokinase and hexokinase expression patterns neither impaired glucose metabolism nor correlated with glucose islet sensitivity, suggesting that β-cell sensitivity to glucose requires secondary events other than the observed metabolic/molecular events. PMID:22034157

  3. The impact of brain function and local glucose metabolism of subthalamic nucleus stimulation in Parkinson's disease patients%丘脑底核电刺激对帕金森病患者脑神经功能及局部糖代谢的影响

    Institute of Scientific and Technical Information of China (English)

    刘丹荣; 胡伟; 尤志珺; 邓超

    2016-01-01

    Objective To investigate the effect of subthalamic nucleus stimulation ( STN-DBS) in Parkinson disease ( PD) brain function in patients with local glucose metabolism abnormal.Methods From June 2011 to June 2014, 60 cases of PD patients in Shiyan people's Hospital, Hubei Medical College were enrolled in this study, they were randomly divided into observation group and control group with 30 cases in each group.Control group was given oral levodopa daily, the observation group based on the treatment in the control group, also added the uplink STN-DBS treatment, before treatment and after treat-ment for 3 months, using Unified Parkinson's Disease Rating Scale ( UPDRS) to assess motor function of patients in two groups respectively, using the Montreal Cognitive Assessment Scale ( MoCA) and mini mental state table ( MMSE) to evaluate neural function and patients were underwent the resting F-deoxyglucose FDG/PET examination.Results Compared with before treat-ment, after treatment, the two groups of patients'UPDRS total score decreased significantly ( P 0.05), and significantly higher in the obser-vation group than the control group ( P 0.05),且观察组显著高于对照组(P<0.05).观察组治疗后每日左旋多巴口服剂量显著少于治疗前及对照组(P<0.05),异动症及运动症状波动发生率显著低于对照组(3.33%vs.26.67%,0 vs.20.00%,P<0.05).结论 STN-DBS能有效改善PD患者各脑区葡糖糖代谢及脑神经功能,促进肢体协调、改善肢体运动功能,提高患者生存质量.

  4. The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Adriaanse, Sofie M. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); VU University Medical Center, Department of Radiology and Nuclear Medicine, Alzheimer Center, Neuroscience Campus Amsterdam, P.O. Box 7057, Amsterdam (Netherlands); Van Dijk, Koene R.A. [Harvard University, Department of Psychology, Center for Brain Science, Cambridge, MA (United States); Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA (United States); Ossenkoppele, Rik; Tolboom, Nelleke; Zwan, Marissa D.; Barkhof, Frederik; Berckel, Bart N.M. van [VU University Medical Center, Department of Radiology and Nuclear Medicine, Alzheimer Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands); Reuter, Martin [Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA (United States); Massachusetts Institute of Technology, Computer Science and Artificial Intelligence Laboratory, Division of Health Sciences and Technology, Cambridge, MA (United States); Yaqub, Maqsood; Boellaard, Ronald; Windhorst, Albert D.; Lammertsma, Adriaan A. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, Amsterdam (Netherlands); Flier, Wiesje M. van der; Scheltens, Philip [VU University Medical Center, Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands)

    2014-06-15

    The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer's disease (AD) patients and healthy elderly controls. Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [{sup 11}C]PIB to assess amyloid-β plaque load and [{sup 18}F]FDG to assess glucose metabolism. [{sup 11}C]PIB binding and [{sup 18}F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho = 0.56, p < 0.05). The present study shows that in a group of AD patients amyloid-β plaque load as measured by [{sup 11}C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [{sup 18}F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration. (orig.)

  5. Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

    OpenAIRE

    Tal, M.; Schneider, D L; Thorens, B.; Lodish, H F

    1990-01-01

    The "erythroid/brain" glucose transporter (GT) isoform is expressed only in a subset of hepatocytes, those forming the first row around the terminal hepatic venules, while the "liver" GT is expressed in all hepatocytes. After 3 d of starvation, a three- to fourfold elevation of expression of the erythroid/brain GT mRNA and protein is detected in the liver as a whole; this correlates with the expression of this GT in more hepatocytes, those forming the first three to four rows around the hepat...

  6. Inflammatory cause of metabolic syndrome via brain stress and NF-κB.

    Science.gov (United States)

    Cai, Dongsheng; Liu, Tiewen

    2012-02-01

    Metabolic syndrome, a network of medical disorders that greatly increase the risk for developing metabolic and cardiovascular diseases, has reached epidemic levels in many areas of today's world. Despite this alarming medicare situation, scientific understandings on the root mechanisms of metabolic syndrome are still limited, and such insufficient knowledge contributes to the relative lack of effective treatments or preventions for related diseases. Recent interdisciplinary studies from neuroendocrinology and neuroimmunology fields have revealed that overnutrition can trigger intracellular stresses to cause inflammatory changes mediated by molecules that control innate immunity. This type of nutrition-related molecular inflammation in the central nervous system, particularly in the hypothalamus, can form a common pathogenic basis for the induction of various metabolic syndrome components such as obesity, insulin resistance, and hypertension. Proinflammatory NF-κB pathway has been revealed as a key molecular system for pathologic induction of brain inflammation, which translates overnutrition and resulting intracellular stresses into central neuroendocrine and neural dysregulations of energy, glucose, and cardiovascular homeostasis, collectively leading to metabolic syndrome. This article reviews recent research advances in the neural mechanisms of metabolic syndrome and related diseases from the perspective of pathogenic induction by intracellular stresses and NF-κB pathway of the brain. PMID:22328600

  7. Cerebral Metabolism Following Traumatic Brain Injury: New Discoveries with Implications for Treatment

    Directory of Open Access Journals (Sweden)

    George A Brooks

    2015-02-01

    Full Text Available Because it is the product of glycolysis and main substrate for mitochondrial respiration, lactate is the central metabolic intermediate in cerebral energy substrate delivery. Our recent studies on healthy controls and patients following TBI using [6,6-2H2]glucose and [3-13C]lactate, along with cerebral blood flow and arterial-venous (jugular bulb difference measurements for oxygen, metabolite levels, isotopic enrichments and 13CO2 show a massive and previously unrecognized mobilization of lactate from corporeal (muscle, skin and other glycogen reserves in TBI patients who were studied 5.72.2 days after injury at which time brain oxygen consumption and glucose uptake (CMRO2 and CMRgluc, respectively were depressed. By tracking the incorporation of the 13C from lactate tracer we found that gluconeogenesis (GNG from lactate accounted for 67.1%, of whole-body glucose appearance rate (Ra in TBI, which was compared to 15.2% in healthy, well-nourished controls. Simultaneous cerebral exchange measurements showed that fractional lactate extraction (FExlac, 12.5% was undiminished following TBI, and as in controls close to 100% of lactate taken up was oxidized in TBI. Hence, 68% of the carbohydrate energy (CHO = glucose + lactate taken up and used by the injured brain came from lactate, either directly by vascular delivery of lactate (9%, or indirectly by GNG from lactate and its contribution to CMRgluc (59%. By comparison, lactate contributed 25% of the CHO energy taken up by brains of healthy postabsorptive control subjects, either directly (12%, or indirectly (13%. As such, a Lactate Shuttle mechanism makes substrate available, both directly and indirectly for the body and brain in healthy individuals and TBI patients. Because CMRlac was maintained, whereas CMRgluc was suppressed following TBI, our recent results support use of exogenous lactate-containing formulations as means to augment nutritive support to the injured brain.

  8. Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo

    OpenAIRE

    Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki; Cook, Michelle; Law, Mona J.; Kaufman, Elaine; Sokoloff, Louis

    2003-01-01

    Neuronal cultures in vitro readily oxidized both D-[14C]glucose and l-[14C]lactate to 14CO2, whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [14C]Glucose oxidation to 14CO2 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 [14C]lactate oxid...

  9. Glucose metabolism and neurogenesis in the gerbil hippocampus after transient forebrain ischemia.

    Science.gov (United States)

    Yoo, Dae Young; Lee, Kwon Young; Park, Joon Ha; Jung, Hyo Young; Kim, Jong Whi; Yoon, Yeo Sung; Won, Moo-Ho; Choi, Jung Hoon; Hwang, In Koo

    2016-08-01

    Recent evidence exists that glucose transporter 3 (GLUT3) plays an important role in the energy metabolism in the brain. Most previous studies have been conducted using focal or hypoxic ischemia models and have focused on changes in GLUT3 expression based on protein and mRNA levels rather than tissue levels. In the present study, we observed change in GLUT3 immunoreactivity in the adult gerbil hippocampus at various time points after 5 minutes of transient forebrain ischemia. In the sham-operated group, GLUT3 immunoreactivity in the hippocampal CA1 region was weak, in the pyramidal cells of the CA1 region increased in a time-dependent fashion 24 hours after ischemia, and in the hippocampal CA1 region decreased significantly between 2 and 5 days after ischemia, with high level of GLUT3 immunoreactivity observed in the CA1 region 10 days after ischemia. In a double immunofluorescence study using GLUT3 and glial-fibrillary acidic protein (GFAP), we observed strong GLUT3 immunoreactivity in the astrocytes. GLUT3 immunoreactivity increased after ischemia and peaked 7 days in the dentate gyrus after ischemia/reperfusion. In a double immunofluorescence study using GLUT3 and doublecortin (DCX), we observed low level of GLUT3 immunoreactivity in the differentiated neuroblasts of the subgranular zone of the dentate gyrus after ischemia. GLUT3 immunoreactivity in the sham-operated group was mainly detected in the subgranular zone of the dentate gyrus. These results suggest that the increase in GLUT3 immunoreactivity may be a compensatory mechanism to modulate glucose level in the hippocampal CA1 region and to promote adult neurogenesis in the dentate gyrus. PMID:27651772

  10. Metabolic network analysis of Bacillus clausii on minimal and semirich medium using C-13-Labeled glucose

    DEFF Research Database (Denmark)

    Christiansen, Torben; Christensen, Bjarke; Nielsen, Jens

    2002-01-01

    or zero flux through PEP carboxykinase was estimated, indicating that the latter enzyme was not active during growth on glucose. The uptake of the amino acids in a semirich medium containing 15 of the 20 amino acids normally present in proteins was estimated using fully labeled glucose in batch...... from the medium and partly synthesized from glucose. The metabolic network analysis was extended to include analysis of growth on the semirich medium containing amino acids, and the metabolic flux distribution on this medium was estimated and compared with growth on minimal medium....... cultivations. It was found that leucine, isoleucine, and phenylalanine were taken up from the medium and not synthesized de novo from glucose. In contrast, serine and threonine were completely synthesized from other metabolites and not taken up from the medium. Valine, proline, and lysine were partly taken up...

  11. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain;

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean...... and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose...

  12. Analysis of Patients With Coronary Heart Disease Combined With Impaired Glucose Metabolism

    Institute of Scientific and Technical Information of China (English)

    Zhi-ping GAO; Li-wen LIE; Ying-ling ZHOU; Hao-jian DONG

    2009-01-01

    Objectives To study the morbidity of patients with coronary artery disease (CAD) combined with impaired glucose metabolism. Methods Retrospective analysis of clinical data about patients with CAD in 1997, 2002 and 2007, sepa-rately. A total of 2951 patients were enrolled, among whom had coexistence of 457 abnormal glycometabolism, inclu-ding impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. Results The prevalence of ab-normal glycometabolism in patients with CAD was increasing year by year. The morbidity raised from 3.8% and 16. 5% to 10. 8% in these three years. Contusion It is more and more common to detect CAD with impaired glucose metabolism, and it should be emphasized in the secondary prevention of CAD.

  13. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan;

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco......RI RFLP) were established using polymerase chain reaction and restriction enzyme digests. The effect of genotypes on lipid levels and on glucose, insulin, and HOMA (i.e., calculated parameters of beta-cell function and insulin resistance) was assessed by multivariate analyses of variance correcting...... for the effect of gender, age, glucose tolerance status, and body mass index. The effect of genotype on the risk of having impaired glucose metabolism was calculated by logistic regression analysis. Finally, linkage between allele sharing and physiological parameters was calculated by the new Haseman...

  14. Changes in metabolism during a fasting period and a subsequent vegetarian diet with particular reference to glucose metabolism.

    Science.gov (United States)

    Lithell, H; Vessby, B; Hellsing, K; Ljunghall, K; Höglund, N J; Werner, I; Bruce, A

    1983-01-01

    During an investigation on the effect of fasting and a vegetarian diet on the symptoms and signs in chronic cutaneous and arthritic diseases studies were made of glucose metabolism, liver function and the plasma concentration and urine excretion of some minerals. The study was performed on 27 patients who stayed as in-patients on a metabolic ward for five weeks. After the fasting period the blood glucose and serum insulin concentrations were lower (p less than 0.01) than before the fast. At the end of the period on the vegetarian (vegan) diet (three weeks) the insulin/glucose ratio was lower than at the start of the fast. Serum enzyme concentrations reflecting liver function increased during the fast, but normalized during the vegan diet. The intake of vitamin B12 and of selenium due to the vegan diets was very low, which may give reason for some concern during long-term use of this type of vegetarian diet.

  15. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

    Science.gov (United States)

    Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

    2016-01-01

    Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; Pbrain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics. PMID:27583555

  16. Profiling the control of hepatic glucose and lipid metabolism for evaluating novel strategies of insulin delivery

    OpenAIRE

    Soares, Ana Francisca Leal Silva

    2011-01-01

    Diabetes mellitus (DM) is a metabolic disorder that results from a dysfunction of insulin secretion (type 1) and/or sensitivity (type 2). Type 1 and in many cases type 2 diabetic patients require daily insulin injections to control blood glucose levels and retard the appearance of diabetes-related complications. The liver plays a central role in the context of whole-body glucose homoeostasis and fuel management in general. Under physiological conditions, insulin is released by the pancr...

  17. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    OpenAIRE

    Kenneth A. Dyar; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus Sjørup; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activit...

  18. Diabetes, Glucose Metabolism, and Glaucoma: The 2005–2008 National Health and Nutrition Examination Survey

    OpenAIRE

    Di Zhao; Juhee Cho; Myung Hun Kim; David Friedman; Eliseo Guallar

    2014-01-01

    BACKGROUND: Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples. OBJECTIVE: To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the gener...

  19. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    OpenAIRE

    Mirco Galiè; Paolo Farace; Cristina Nanni; Antonello Spinelli; Elena Nicolato; Federico Boschi; Paolo Magnani; Silvia Trespidi; Valentina Ambrosini; Stefano Fanti; Flavia Merigo; Francesco Osculati; Pasquina Marzola; Andrea Sbarbati

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular ...

  20. Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R;

    1995-01-01

    < .02) and the rate of insulin-stimulated glucose disposal to peripheral tissues was lower in patients with MA (13.4 +/- 1.0 v 18.2 +/- 1.4 mg.kg fat-free mass [FFM]-1.min-1, P < .02) due to a decrease in nonoxidative glucose metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P < .02). No...

  1. Glucose metabolism in small subcortical structures in Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Hansen, Søren B; Eggers, Carsten;

    2012-01-01

    Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PET...

  2. Oxidative stress in the etiology of age-associated decline in glucose metabolism.

    Science.gov (United States)

    Salmon, Adam B

    2012-01-01

    One of the most common pathologies in aging humans is the development of glucose metabolism dysfunction. The high incidence of metabolic dysfunction, in particular type 2 diabetes mellitus, is a significant health and economic burden on the aging population. However, the mechanisms that regulate this age-related physiological decline, and thus potential preventative treatments, remain elusive. Even after accounting for age-related changes in adiposity, lean mass, blood lipids, etc., aging is an independent factor for reduced glucose tolerance and increased insulin resistance. Oxidative stress has been shown to have significant detrimental impacts on the regulation of glucose homeostasis in vitro and in vivo. Furthermore, oxidative stress has been shown to be modulated by age and diet in several model systems. This review provides an overview of these data and addresses whether increases in oxidative stress with aging may be a primary determinant of age-related metabolic dysfunction.

  3. Ascorbic acid recycling by cultured beta cells: effects of increased glucose metabolism.

    Science.gov (United States)

    Steffner, Robert J; Wu, Lan; Powers, Alvin C; May, James M

    2004-11-15

    Ascorbic acid is necessary for optimal insulin secretion from pancreatic islets. We evaluated ascorbate recycling and whether it is impaired by increased glucose metabolism in the rat beta-cell line INS-1. INS-1 cells, engineered with the potential for overexpression of glucokinase under the control of a tetracycline-inducible gene expression system, took up and reduced dehydroascorbic acid to ascorbate in a concentration-dependent manner that was optimal in the presence of physiologic D-glucose concentrations. Ascorbate uptake did not affect intracellular GSH concentrations. Whereas depletion of GSH in culture to levels about 25% of normal also did not affect the ability of the cells to reduce dehydroascorbic acid, more severe acute GSH depletion to less than 10% of normal levels did impair dehydroascorbic acid reduction. Culture of inducible cells in 11.8 mM D-glucose and doxycycline for 48 h enhanced glucokinase activity, increased glucose utilization, abolished D-glucose-dependent insulin secretion, and increased generation of reactive oxygen species. The latter may have contributed to subsequent decreases in the ability of the cells both to maintain intracellular ascorbate and to recycle it from dehydroascorbic acid. Cultured beta cells have a high capacity to recycle ascorbate, but this is sensitive to oxidant stress generated by increased glucose metabolism due to culture in high glucose concentrations and increased glucokinase expression. Impaired ascorbate recycling as a result of increased glucose metabolism may have implications for the role of ascorbate in insulin secretion in diabetes mellitus and may partially explain glucose toxicity in beta cells. PMID:15477012

  4. Berberine Improves Glucose Metabolism through Induction of Glycolysis

    OpenAIRE

    Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping

    2007-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has been reported to activate AMPK recently. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after five week administration. Fasting insulin and HOMA-IR were decreased by 46% and 48% in the rats, respectively. In cell lines includin...

  5. 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

    selected areas by 48-71% of the baseline (P< or = 0.01), with the most significant reductions in the lingual gyrus (71%), occipital lobe in general (68%) and thalamus (63%). No increases in rGMR were observed. CONCLUSIONS: Sevoflurane caused a global whole-brain 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....

  6. Germ band retraction as a landmark in glucose metabolism during Aedes aegypti embryogenesis

    Directory of Open Access Journals (Sweden)

    Logullo Carlos

    2010-02-01

    Full Text Available Abstract Background The mosquito A. aegypti is vector of dengue and other viruses. New methods of vector control are needed and can be achieved by a better understanding of the life cycle of this insect. Embryogenesis is a part of A. aegypty life cycle that is poorly understood. In insects in general and in mosquitoes in particular energetic metabolism is well studied during oogenesis, when the oocyte exhibits fast growth, accumulating carbohydrates, lipids and proteins that will meet the regulatory and metabolic needs of the developing embryo. On the other hand, events related with energetic metabolism during A. aegypti embryogenesis are unknown. Results Glucose metabolism was investigated throughout Aedes aegypti (Diptera embryonic development. Both cellular blastoderm formation (CBf, 5 h after egg laying - HAE and germ band retraction (GBr, 24 HAE may be considered landmarks regarding glucose 6-phosphate (G6P destination. We observed high levels of glucose 6-phosphate dehydrogenase (G6PDH activity at the very beginning of embryogenesis, which nevertheless decreased up to 5 HAE. This activity is correlated with the need for nucleotide precursors generated by the pentose phosphate pathway (PPP, of which G6PDH is the key enzyme. We suggest the synchronism of egg metabolism with carbohydrate distribution based on the decreasing levels of phosphoenolpyruvate carboxykinase (PEPCK activity and on the elevation observed in protein content up to 24 HAE. Concomitantly, increasing levels of hexokinase (HK and pyruvate kinase (PK activity were observed, and PEPCK reached a peak around 48 HAE. Glycogen synthase kinase (GSK3 activity was also monitored and shown to be inversely correlated with glycogen distribution during embryogenesis. Conclusions The results herein support the hypothesis that glucose metabolic fate changes according to developmental embryonic stages. Germ band retraction is a moment that was characterized as a landmark in glucose

  7. Plasma Glucose and Serum Ceruloplasmin in Metabolic Syndrome and Diabetes Mellitus Type 2

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Jeppu

    2016-04-01

    Full Text Available Diabetes mellitus type 2 and metabolic syndrome are conditions associated with insulin resistance and hyperglycemia. Metabolic syndrome is a risk factor for diabetes mellitus type 2. Plasma glucose (fasting/postprandial and serum ceruloplasmin levels and their relationship were studied. Study population consisted of 150 individuals—50 individuals with diabetes mellitus type 2, 50 individuals with metabolic syndrome, and 50 age- and sex-matched healthy controls. Plasma levels of fasting and postprandial glucose were measured along with serum ceruloplasmin. Data was analyzed by ANOVA and Pearson correlation. The fasting and postprandial plasma glucose levels in metabolic syndrome and diabetes mellitus type 2 were increased when compared to control. Serum ceruloplasmin level was 327.8 ± 68.9 in control, 227.3 ± 46.8 in metabolic syndrome, and 194.0 ± 49.6 in diabetes mellitus type 2 individuals. There was a statistically significant negative correlation between the fasting, postprandial plasma glucose, and serum ceruloplasmin in type 2 diabetes mellitus.

  8. Changes in brain oxidative metabolism induced by water maze training.

    Science.gov (United States)

    Conejo, N M; González-Pardo, H; Vallejo, G; Arias, J L

    2007-03-16

    Although the hippocampus has been shown to be essential for spatial memory, the contribution of associated brain regions is not well established. Wistar rats were trained to find a hidden escape platform in the water maze during eight days. Following training, the oxidative metabolism in different brain regions was evaluated using cytochrome oxidase histochemistry. Metabolic activations were found in the prelimbic cortex, cornu ammonis (CA) 1 subfield of the dorsal hippocampus and the anterior thalamic nuclei, relative to yoked swim controls and naïve rats. In addition, many cross-correlations in brain metabolism were observed among the latter regions. These results support the implication of a hippocampal-prefrontal-thalamic system to spatial memory in rats. PMID:17222984

  9. DLK1 Regulates Whole-Body Glucose Metabolism

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge;

    2015-01-01

    The endocrine role of the skeleton in regulating energy metabolism is supported by a feed-forward loop between circulating osteoblast (OB)-derived undercarboxylated osteocalcin (Glu-OCN) and pancreatic β-cell insulin; in turn, insulin favors osteocalcin (OCN) bioactivity. These data suggest...... 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...

  10. DMH1 increases glucose metabolism through activating Akt in L6 rat skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Xin Xie

    Full Text Available DMH1(4-[6-(4-Isopropoxyphenylpyrazolo [1,5-a]pyrimidin-3-yl] quinoline is a compound C analogue with the structural modifications at the 3- and 6-positions in pyrazolo[1,5-a]pyrimidine backbone. Compound C was reported to inhibit both AMPK and Akt. Our preliminary work found that DMH1 activated Akt. Since Akt was involved in glucose metabolism, we aimed to identify the effects of DMH1 on glucose metabolism in L6 rat muscle cells and the potential mechanism. Results showed that DMH1 increased lactic acid release and glucose consumption in L6 rat muscle cells in a dose-dependent manner. DMH1 activated Akt in L6 cells. Akt inhibitor inhibited DMH1-induced Akt activation and DMH1-induced increases of glucose uptake and consumption. DMH1 had no cytotoxicity in L6 cells, but inhibited mitochondrial function and reduced ATP production. DMH1 showed no effect on AMPK, but in the presence of Akt inhibitor, DMH1 significantly activated AMPK. Compound C inhibited DMH1-induced Akt activation in L6 cells. Compound C inhibited DMH1-induced increase of glucose uptake, consumption and lactic acid release in L6 cells. DMH1 inhibited PP2A activity, and PP2A activator forskolin reversed DMH1-induced Akt activation. We concluded that DMH1 increased glucose metabolism through activating Akt and DMH1 activated Akt through inhibiting PP2A activity in L6 rat muscle cells. In view of the analogue structure of DMH1 and compound C and the contrasting effects of DMH1 and compound C on Akt, the present study provides a novel leading chemical structure targeting Akt with potential use for regulating glucose metabolism.

  11. Analysis of oral glucose tolerance test in pregnant women with abnormal glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    YANG Hui-xia; GAO Xue-lian; DONG Yue; SHI Chun-yan

    2005-01-01

    Background Due to the controversy of the oral glucose tolerance test (OGTT), diagnostic criteria for gestational diabetes mellitus (GDM) in the world and researches on GDM remain undeveloped in China. American Diabetes Association recently recommended the clinicians to diagnose GDM by OGTT results without the third-hour glucose value. This new criteria has not been used in China. Research on the value and sensitivity of the criteria in detecting GDM is rare. The aim of our study is to analyze the characteristics of OGTT in Chinese women with GDM or gestational impaired glucose tolerance (GIGT) and to evaluate the effect of omission of the third-hour plasma glucose (PG) level in OGTT on the sensitivity of diagnosing GDM and GIGT, and the relationship between PG values of 50 g GCT or OGTT and insulin therapy. Methods A retrospective analysis was performed on medical records of 647 cases with GDM from January 1, 1989 to December 31, 2002, and 233 with GIGT. Among 647 cases of GDM, 535 cases were diagnosed by 75 g OGTT. All OGTT results including 535 cases of GDM and 233 patients with GIGT were evaluated. Results There were 112 cases of GDM diagnosed by elevated fasting PG (FPG) without OGTT performed. Of 535 cases of GDM diagnosed by OGTT, 49.2% (263/535) women had FPG value ≥5.8 mmol/L; 90.1% (482/535) women with 1-hour PG values ≥10.6 mmol/L; 64.7% (359/535) with 2-hour PG levels ≥9.2 mmol/L. There were only 114 cases (21.3%) with abnormal 3-hour PG levels among 535 women with OGTT. Among those with abnormal 3-hour PG level, 49.1% (56/114) had abnormal glucose values in the other three points of OGTT, and 34.2% (39/114) with two other abnormal values of OGTT. Our study showed that omission of the 3-hour PG of OGTT only missed 19 cases of GDM and they would be diagnosed as GIGT. Among the 233 women with GIGT, only 4 cases had abnormal 3-hour PG. So, omission of the third-hour glucose value of OGTT only resulted in failure to diagnose 3.6% (19/535) women with

  12. The effect of vagal nerve blockade using electrical impulses on glucose metabolism in nondiabetic subjects

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    Sathananthan M

    2014-07-01

    Full Text Available Matheni Sathananthan,1 Sayeed Ikramuddin,2 James M Swain,3,6 Meera Shah,1 Francesca Piccinini,4 Chiara Dalla Man,4 Claudio Cobelli,4 Robert A Rizza,1 Michael Camilleri,5 Adrian Vella1 1Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA; 2Division of General Surgery, University of Minnesota, Minneapolis, MN, USA; 3Division of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA; 4Department of Information Engineering, University of Padua, Padua, Italy; 5Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA; 6Scottsdale Healthcare Bariatric Center, Scottsdale, AZ, USA Purpose: Vagal interruption causes weight loss in humans and decreases endogenous glucose production in animals. However, it is unknown if this is due to a direct effect on glucose metabolism. We sought to determine if vagal blockade using electrical impulses alters glucose metabolism in humans. Patients and methods: We utilized a randomized, cross-over study design where participants were studied after 2 weeks of activation or inactivation of vagal nerve blockade (VNB. Seven obese subjects with impaired fasting glucose previously enrolled in a long-term study to examine the effect of VNB on weight took part. We used a standardized triple-tracer mixed meal to enable measurement of the rate of meal appearance, endogenous glucose production, and glucose disappearance. The 550 kcal meal was also labeled with 111In-diethylene triamine pentaacetic acid (DTPA to measure gastrointestinal transit. Insulin action and ß-cell responsivity indices were estimated using the minimal model. Results: Integrated glucose, insulin, and glucagon concentrations did not differ between study days. This was also reflected in a lack of effect on β-cell responsivity and insulin action. Furthermore, fasting and postprandial endogenous glucose production, integrated meal appearance, and glucose

  13. Glutamate metabolism in the brain focusing on astrocytes

    DEFF Research Database (Denmark)

    Schousboe, Arne; Scafidi, Susanna; Bak, Lasse Kristoffer;

    2014-01-01

    Metabolism of glutamate, the main excitatory neurotransmitter and precursor of GABA, is exceedingly complex and highly compartmentalized in brain. Maintenance of these neurotransmitter pools is strictly dependent on the de novo synthesis of glutamine in astrocytes which requires both the anaplero......Metabolism of glutamate, the main excitatory neurotransmitter and precursor of GABA, is exceedingly complex and highly compartmentalized in brain. Maintenance of these neurotransmitter pools is strictly dependent on the de novo synthesis of glutamine in astrocytes which requires both......, as well as in nitrogen trafficking and ammonia homeostasis in brain. The anatomical specialization of astrocytic endfeet enables these cells to rapidly and efficiently remove neurotransmitters from the synaptic cleft to maintain homeostasis, and to provide glutamine to replenish neurotransmitter pools...... summarizes the evidence that astrocytes are essential and dynamic partners in both glutamatergic and GABAergic neurotransmission in brain....

  14. Magnetic resonance and the human brain: anatomy, function and metabolism.

    Science.gov (United States)

    Talos, I-F; Mian, A Z; Zou, K H; Hsu, L; Goldberg-Zimring, D; Haker, S; Bhagwat, J G; Mulkern, R V

    2006-05-01

    The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth. PMID:16568243

  15. Metabolic glucose status and pituitary pathology portend therapeutic outcomes in acromegaly.

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    Sonia Cheng

    Full Text Available INTRODUCTION: Acromegaly is frequently associated with impaired glucose tolerance and/or diabetes. To evaluate the relationship between glucose metabolism and acromegaly disease, we evaluated 269 consecutive patients from two referral centres. METHODS: Clinical presentation, pituitary tumor size and invasiveness, and pituitary pathology were captured in a dedicated database. RESULTS: 131 women and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7% presented with a macroadenoma and 18 (6.7% with a microadenoma. Radiographic invasion was present in 91 cases (33.8%. Mean tumor diameter was 1.86 cm (0.2-4.6. Pituitary histopathologic findings revealed pure GH-producing somatotroph adenomas (SA in 147 patients, prolactin-production by mixed lactotroph (LA and SA or mammosomatotroph adenoma (MSA in 46 [22.4%], acidophil stem cell adenoma in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly, patients with pure somatotroph adenomas were significantly more likely to present with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%] [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose metabolism and pituitary pathology also remained linked following IGF-1 normalization. Moreover patients with pure SA and abnormal glucose metabolism were significantly (p<0.001 less likely to achieve disease remission despite the same therapeutic strategies. Conversely, patients with mixed adenomas were more likely (OR: 2.766 (95% CI: 1.490-5.136 to achieve disease remission. CONCLUSIONS: Patients with pure somatotroph adenomas are more likely than those with mixed adenomas to exhibit abnormal glucose metabolism.

  16. The Lin28/let-7 Axis Regulates Glucose Metabolism

    NARCIS (Netherlands)

    Zhu, Hao; Shyh-Chang, Ng; Segre, 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.

    2011-01-01

    The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating-metabolism. When overexpressed in mice, both Lin28

  17. The characteristics of cortical glucose metabolism in amblyopia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ji Young [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lee, Dong Soo; Chung, June Key; Shin, Seung Ai; Lee, Myung Chul [College of Medicine, Ewha Womans Univ., Seoul (Korea, Republic of)

    2000-07-01

    Cortical metabolism of amblyopia patients was investigated with F-18-FDG PET and Statistical Parametric Mapping (SPM) and quantificiation based on volume of interest (VOI) by statistical probabilistic anatomical map (SPAM). In 9 amblyopic patients (12{+-}7 years ) and 20 normal subjects (23{+-}2 years), F-18-FDG PET scans were peformed in amblyopic patients after amblyopic eye or sound eye was patch-closed during PET studies. SPM was done with SPM96. By multiplying SPAM to FDG images, counts of 98 VOI's were calculated and compared with 3 S. D. range of those of normal subjects. On SPM, cortical metabolism decreased (p<0.05) in occipital lobe (Ba 17, 18, 19), superior partietal lobe (Ba 7), and inferior temporal lobe (BA 37, 20). FDG uptake of gyri of occuipital lobe was decreased in 2 and increased in 2, and was normal in the other 5. FDG uptake of gyri of parietal, frontal, and temporal lobes were decreased in FDG uptake on these VOIs. We conclude that cortical metabolism in occipital lobe and extraoccipital lobes was variable but was consistent regardless of visual input during PET studies in amblyopic patients. SPM and quantification of functional images using SPAM could reveal subtle differences or changes according to visual input. The significance of metabolic changes of extraoccipital lobes should be studies further.

  18. Cortical Glucose Metabolism Positively Correlates with Gamma-Oscillations in Nonlesional Focal Epilepsy

    OpenAIRE

    Nishida, Masaaki; Juhász, Csaba; Sood, Sandeep; Chugani, Harry T.; Asano, Eishi

    2008-01-01

    Why do the epileptogenic foci appear hypometabolic on interictal glucose metabolism positron emission tomography (PET) in a substantial proportion of patients with focal epilepsy but appear normo- or even hyper-metabolic in others? Such observations on interictal PET have not been fully explained by the frequency of interictal spike discharges alone. In the present study using digital electrocorticography monitoring system with high-frequency sampling, we determined how well regression models...

  19. TAp63 is a master transcriptional regulator of lipid and glucose metabolism

    OpenAIRE

    Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y.; Flores, Elsa R.

    2012-01-01

    TAp63 prevents premature aging suggesting a link to genes that regulate longevity. Further characterization of TAp63−/− mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance, similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulati...

  20. Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism

    OpenAIRE

    Kim, Ho-Seong

    2013-01-01

    Insulin-like growth factor binding protein (IGFBP)-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFB...

  1. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography

    International Nuclear Information System (INIS)

    While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (13N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-05-01

    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. Magnesium enhances exercise performance via increasing glucose availability in the blood, muscle, and brain during exercise.

    Directory of Open Access Journals (Sweden)

    Hsuan-Ying Chen

    Full Text Available Glucose mobilization and utilization in the periphery and central nervous system are important during exercise and are responsible for exercise efficacy. Magnesium (Mg is involved in energy production and plays a role in exercise performance. This study aimed to explore the effects of Mg on the dynamic changes in glucose and lactate levels in the muscle, blood and brain of exercising rats using a combination of auto-blood sampling and microdialysis. Sprague-Dawley rats were pretreated with saline or magnesium sulfate (MgSO4, 90 mg/kg, i.p. 30 min before treadmill exercise (20 m/min for 60 min. Our results indicated that the muscle, blood, and brain glucose levels immediately increased during exercise, and then gradually decreased to near basal levels in the recovery periods of both groups. These glucose levels were significantly enhanced to approximately two-fold (P<0.05 in the Mg group. Lactate levels in the muscle, blood, and brain rapidly and significantly increased in both groups during exercise, and brain lactate levels in the Mg group further elevated (P<0.05 than those in the control group during exercise. Lactate levels significantly decreased after exercise in both groups. In conclusion, Mg enhanced glucose availability in the peripheral and central systems, and increased lactate clearance in the muscle during exercise.

  4. Bile Acid Sequestration Reduces Plasma Glucose Levels in db/db Mice by Increasing Its Metabolic Clearance Rate

    NARCIS (Netherlands)

    Meissner, M.; Herrema, H.J.; Dijk, van Th.; Gerding, A.; Havinga, R.; Boer, T.; Müller, M.R.; Reijngoud, D.J.; Groen, A.K.; Kuipers, F.

    2011-01-01

    Aims/Hypothesis: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore

  5. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.

    Science.gov (United States)

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p equivalents, p metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

  6. An in vitro assessment of the effect of Athrixia phylicoides DC. aqueous extract on glucose metabolism.

    Science.gov (United States)

    Chellan, N; Muller, C J F; de Beer, D; Joubert, E; Page, B J; Louw, J

    2012-06-15

    Athrixia phylicoides DC. is an aromatic shrub indigenous to the eastern parts of Southern Africa. Indigenous communities brew "bush tea" from dried twigs and leaves of A. phylicoides, which is consumed as a beverage and used for its medicinal properties. Plant polyphenols have been shown to be beneficial to Type 2 diabetes mellitus (T2D) and obesity. Aqueous extracts of the plant have been shown to be rich in polyphenols, in particular phenolic acids, which may enhance glucose uptake and metabolism. The aim of this study was to determine the phenolic composition of a hot water A. phylicoides extract and assess its in vitro effect on cellular glucose utilisation. The most abundant phenolic compounds in the extract were 6-hydroxyluteolin-7-O-glucoside, chlorogenic acid, protocatechuic acid, a di-caffeoylquinic acid and a methoxy-flavonol derivative. The extract increased glucose uptake in C2C12, Chang and 3T3-L1 cells, respectively. Intracellular glucose was utilised by both oxidation (C2C12 myocytes and Chang cells; p < 0.01 and p < 0.05, respectively) and by increased glycogen storage (Chang cells; p < 0.05). No cytotoxicity was observed in Chang cells at the concentrations tested. The effects of the extract were not dose-dependent. A. phylicoides aqueous extract stimulated in vitro glucose uptake and metabolism, suggesting that consumption of this phenolic-rich extract could potentially ameliorate metabolic disorders related to obesity and T2D. PMID:22516895

  7. Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Yasuhiko Minokoshi

    2012-01-01

    Full Text Available Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulation of food intake, energy expenditure, and neuroendocrine function. Several lines of evidences indicate that independent of the anorexic effect, leptin regulates glucose and lipid metabolism in peripheral tissues in rodents and humans. It has been shown that leptin improves the diabetes phenotype in lipodystrophic patients and rodents. Moreover, leptin suppresses the development of severe, progressive impairment of glucose metabolism in insulin-deficient diabetes in rodents. We found that leptin increases glucose uptake and fatty acid oxidation in skeletal muscle in rats and mice in vivo. Leptin increases glucose uptake in skeletal muscle via the hypothalamic-sympathetic nervous system axis and β-adrenergic mechanism, while leptin stimulates fatty acid oxidation in muscle via AMP-activated protein kinase (AMPK. Leptin-induced fatty acid oxidation results in the decrease of lipid accumulation in muscle, which can lead to functional impairments called as "lipotoxicity." Activation of AMPK occurs by direct action of leptin on muscle and through the medial hypothalamus-sympathetic nervous system and α-adrenergic mechanism. Thus, leptin plays an important role in the regulation of glucose and fatty acid metabolism in skeletal muscle.

  8. The metabolic syndrome: a brain disease?

    NARCIS (Netherlands)

    Buijs, R.M.; Kreier, F.

    2006-01-01

    The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia--the metabolic syndrome--is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each

  9. Blast overpressure waves induce transient anxiety and regional changes in cerebral glucose metabolism and delayed hyperarousal in rats

    Directory of Open Access Journals (Sweden)

    Hibah Omar Awwad

    2015-06-01

    Full Text Available Physiological alterations, anxiety and cognitive disorders are strongly associated with blast-induced traumatic brain injury (blast TBI and are common symptoms in service personnel exposed to blasts. Since 2006, 25-30,000 new TBI cases are diagnosed annually in U.S. Service members; increasing evidence confirms that primary blast exposure causes diffuse axonal injury and is often accompanied by altered behavioral outcomes. Behavioral and acute metabolic effects resulting from blast to the head in the absence of thoracic contributions from the periphery were examined following a single blast wave directed to the head of male Sprague-Dawley rats protected by a lead shield over the torso. An 80 psi head blast produced cognitive deficits that were detected in working memory. Blast TBI rats displayed increased anxiety as determined by elevated plus maze at day 9 post-blast compared to sham rats; blast TBI rats spent significantly more time than the sham controls in the closed arms (p<0.05; n=8-11. Interestingly, anxiety symptoms were absent at days 22 and 48 post-blast. Instead, blast TBI rats displayed hyperactivity and increased rearing behavior at day 48 post-blast compared to sham rats. Blast TBI rats also exhibited suppressed acoustic startle responses, but similar pre-pulse inhibition at day 15 post-blast compared to sham rats. Acute physiological alterations in cerebral glucose metabolism were determined by positron emission tomography 1 and 9 days post-blast using F-18-fluorodeoxyglucose. Global glucose uptake in blast TBI rat brains increased at day 1 post-blast (p<0.05; n=4-6 and returned to sham levels by day 9. Our results indicate a transient increase in cerebral metabolism following a blast injury. Markers for reactive astrogliosis and neuronal damage were noted by immunoblotting motor cortex tissue from day 10 post-blast in blast TBI rats compared to sham controls (p<0.05; n=5-6.

  10. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    OpenAIRE

    Su, Hong; Bo ZHOU; Ya-qian DUAN; Du, Chao

    2013-01-01

    Objective  To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3) and Ac-H4 in human renal mesangial cell (HMCs) as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods  The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d), high glucose group (HG, 25mmol/L D-glucose×2d), memory groups (M1, M2, M3, 25mmol/L...

  11. Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-hour glucose and insulin excursions

    Science.gov (United States)

    It has been proposed that the adverse metabolic effects of chronic consumption of sugar-sweetened beverages which contain both glucose and fructose are a consequence of increased circulating glucose and insulin excursions, i.e dietary glycemic index (GI). Objective: We determined if the greater adv...

  12. Computational modeling of glucose transport in pancreatic β-cells identifies metabolic thresholds and therapeutic targets in diabetes.

    Directory of Open Access Journals (Sweden)

    Camilla Luni

    Full Text Available Pancreatic β-cell dysfunction is a diagnostic criterion of Type 2 diabetes and includes defects in glucose transport and insulin secretion. In healthy individuals, β-cells maintain plasma glucose concentrations within a narrow range in concert with insulin action among multiple tissues. Postprandial elevations in blood glucose facilitate glucose uptake into β-cells by diffusion through glucose transporters residing at the plasma membrane. Glucose transport is essential for glycolysis and glucose-stimulated insulin secretion. In human Type 2 diabetes and in the mouse model of obesity-associated diabetes, a marked deficiency of β-cell glucose transporters and glucose uptake occurs with the loss of glucose-stimulated insulin secretion. Recent studies have shown that the preservation of glucose transport in β-cells maintains normal insulin secretion and blocks the development of obesity-associated diabetes. To further elucidate the underlying mechanisms, we have constructed a computational model of human β-cell glucose transport in health and in Type 2 diabetes, and present a systems analysis based on experimental results from human and animal studies. Our findings identify a metabolic threshold or "tipping point" whereby diminished glucose transport across the plasma membrane of β-cells limits intracellular glucose-6-phosphate production by glucokinase. This metabolic threshold is crossed in Type 2 diabetes and results in β-cell dysfunction including the loss of glucose stimulated insulin secretion. Our model further discriminates among molecular control points in this pathway wherein maximal therapeutic intervention is achieved.

  13. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism.

    Science.gov (United States)

    Hao, Qin; Yadav, Rachita; Basse, Astrid L; Petersen, Sidsel; Sonne, Si B; Rasmussen, Simon; Zhu, Qianhua; Lu, Zhike; Wang, Jun; Audouze, Karine; Gupta, Ramneek; Madsen, Lise; Kristiansen, Karsten; Hansen, Jacob B

    2015-03-01

    We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen metabolism, and the pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol-3-phosphate dehydrogenase 1 expression was induced in BAT from cold-challenged mice, suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold. Of notice, only a subset of the changes detected in BAT was observed in WAT. Based on changes in gene expression during cold exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating triacylglycerol synthesis/fatty acid re-esterification; 3) glycogen turnover and lactate production are increased; and 4) entry of glucose carbon into the tricarboxylic acid cycle is restricted by PDK2 and PDK4. In summary, our results demonstrate extensive and diverse gene expression changes related to glucose handling in activated BAT. PMID:25516548

  14. Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate

    Institute of Scientific and Technical Information of China (English)

    CAI Xiao-ling; HAN Xue-yao; JI Li-nong

    2010-01-01

    Background Recently, it has been suggested that the serum uric acid (SUA) level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate (GFR) reflected by the simplified Modification of Diet in Renal Disease (MDRD) equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.Methods This cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test (OGTT) for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.Results Multiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index (BMI), waist/hippo ratio, systolic blood pressure (SBP) and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose (FPG) increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.Conclusion This study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.

  15. Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

    Science.gov (United States)

    Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

    1986-01-01

    Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

  16. Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

    Directory of Open Access Journals (Sweden)

    John A Findlay

    2015-10-01

    Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  17. Non-Classical Gluconeogenesis-Dependent Glucose Metabolism in Rhipicephalus microplus Embryonic Cell Line BME26

    Directory of Open Access Journals (Sweden)

    Renato Martins da Silva

    2015-01-01

    Full Text Available In this work we evaluated several genes involved in gluconeogenesis, glycolysis and glycogen metabolism, the major pathways for carbohydrate catabolism and anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by alterations in energy resource availability (primarily glucose. BME26 cells in media were investigated using three different glucose concentrations, and changes in the transcription levels of target genes in response to carbohydrate utilization were assessed. The results indicate that several genes, such as glycogen synthase (GS, glycogen synthase kinase 3 (GSK3, phosphoenolpyruvate carboxykinase (PEPCK, and glucose-6 phosphatase (GP displayed mutual regulation in response to glucose treatment. Surprisingly, the transcription of gluconeogenic enzymes was found to increase alongside that of glycolytic enzymes, especially pyruvate kinase, with high glucose treatment. In addition, RNAi data from this study revealed that the transcription of gluconeogenic genes in BME26 cells is controlled by GSK-3. Collectively, these results improve our understanding of how glucose metabolism is regulated at the genetic level in tick cells.

  18. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

    Directory of Open Access Journals (Sweden)

    Xuan Xia

    Full Text Available Berberine (BBR is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French. It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK and Glucose-6-phosphatase (G6Pase, were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1, sterol regulatory element-binding protein 1c (SREBP1 and carbohydrate responsive element-binding protein (ChREBP were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

  19. Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses

    Science.gov (United States)

    Ilievski, Vladimir; Kinchen, Jason M; Prabhu, Ramya; Rim, Fadi; Leoni, Lara; Unterman, Terry G.; Watanabe, Keiko

    2016-01-01

    Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis. Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4-ethylphenylsulfate sulfate in animals with periodontitis. The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the

  20. Role of gut microbiota in maternal glucose metabolism

    OpenAIRE

    Mao, Yushi; 毛雨詩

    2015-01-01

    Gut microbiota plays an important role in daily biological reactions. It is proved that many metabolic diseases are accompanied with pattern change of gut microbiota and pregnancy is also a process with gut microbiota remodeling. Besides, serum IGF-1 level is increased during pregnancy, but the source of increased IGF-1 remains unclear. So far, there is a paper that explored the gut microbiota in pregnant women. However, the diet of pregnant women was not unified in the study, which might hav...

  1. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    OpenAIRE

    2015-01-01

    Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG), sclerostin (SOST), and Dickopf (DKK) which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, suc...

  2. Low non-oxidative glucose metabolism and violent offending: an 8-year prospective follow-up study.

    Science.gov (United States)

    Virkkunen, Matti; Rissanen, Aila; Franssila-Kallunki, Anja; Tiihonen, Jari

    2009-06-30

    Violent offenders have abnormalities in their glucose metabolism as indicated by decreased glucose uptake in their prefrontal cortex and a low blood glucose nadir in the glucose tolerance test. We tested the hypothesis that low non-oxidative glucose metabolism (NOG) predicts forthcoming violent offending among antisocial males. Glucose metabolism was measured using the insulin clamp method among 49 impulsive, violent, antisocial offenders during a forensic psychiatric examination. Those offenders who committed at least one new violent crime during the 8-year follow-up had a mean NOG of 1.4 standard deviations lower than non-recidivistic offenders. In logistic regression analysis, NOG alone explained 27% of the variation in the recidivistic offending. Low non-oxidative metabolism may be a crucial component in the pathophysiology of habitually violent behavior among subjects with antisocial personality disorder. This might suggest that substances increasing glycogen formation and decreasing the risk of hypoglycemia might be potential treatments for impulsive violent behavior. PMID:19446886

  3. Metabolism as a tool for understanding human brain evolution: lipid energy metabolism as an example.

    Science.gov (United States)

    Wang, Shu Pei; Yang, Hao; Wu, Jiang Wei; Gauthier, Nicolas; Fukao, Toshiyuki; Mitchell, Grant A

    2014-12-01

    Genes and the environment both influence the metabolic processes that determine fitness. To illustrate the importance of metabolism for human brain evolution and health, we use the example of lipid energy metabolism, i.e. the use of fat (lipid) to produce energy and the advantages that this metabolic pathway provides for the brain during environmental energy shortage. We briefly describe some features of metabolism in ancestral organisms, which provided a molecular toolkit for later development. In modern humans, lipid energy metabolism is a regulated multi-organ pathway that links triglycerides in fat tissue to the mitochondria of many tissues including the brain. Three important control points are each suppressed by insulin. (1) Lipid reserves in adipose tissue are released by lipolysis during fasting and stress, producing fatty acids (FAs) which circulate in the blood and are taken up by cells. (2) FA oxidation. Mitochondrial entry is controlled by carnitine palmitoyl transferase 1 (CPT1). Inside the mitochondria, FAs undergo beta oxidation and energy production in the Krebs cycle and respiratory chain. (3) In liver mitochondria, the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) pathway produces ketone bodies for the brain and other organs. Unlike most tissues, the brain does not capture and metabolize circulating FAs for energy production. However, the brain can use ketone bodies for energy. We discuss two examples of genetic metabolic traits that may be advantageous under most conditions but deleterious in others. (1) A CPT1A variant prevalent in Inuit people may allow increased FA oxidation under nonfasting conditions but also predispose to hypoglycemic episodes. (2) The thrifty genotype theory, which holds that energy expenditure is efficient so as to maximize energy stores, predicts that these adaptations may enhance survival in periods of famine but predispose to obesity in modern dietary environments.

  4. Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella

    DEFF Research Database (Denmark)

    Kovatcheva-Datchary, Petia; Nilsson, Anne; Akrami, Rozita;

    2015-01-01

    The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day cons...

  5. Disturbed postprandial glucose metabolism and gut hormone responses in non-diabetic patients with psoriasis

    DEFF Research Database (Denmark)

    Gyldenløve, M; Vilsbøll, T; Holst, Jens Juul;

    2016-01-01

    Patients with psoriasis have increased risk of developing type 2 diabetes.(1-4) Though the aetiology is not fully understood, overrepresentation of traditional diabetes risk factors, shared genetics, and chronic inflammation likely explain some of the increased susceptibility. Glucose metabolism ...

  6. Glucose and maltose metabolism in MIG1-disrupted and MAL-constitutive strains of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Klein, Christopher; Olsson, Lisbeth; Rønnow, B;

    1997-01-01

    The alleviation of glucose control of maltose metabolism brought about by MIG1 disruption was compared to that by MAL overexpression in a haploid Saccharomyces cerevisiae strain. The sugar consumption profiles during cultivation of the wild type, single transformants and a double transformant in ...

  7. Polychlorinated Biphenyl Exposure and Glucose Metabolism in 9-Year-Old Danish Children

    DEFF Research Database (Denmark)

    Jensen, Tina K.; Timmermann, Amalie G.; Rossing, Laura I.;

    2014-01-01

    Context: Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. Objectives: To determine whether concurrent serum PCB concentration was associated with markers of glucose metabolism in healthy children. Design: Cross-sectional study. Settings and part...

  8. Sleep deprivation and its impact on circadian rhythms and glucose metabolism

    NARCIS (Netherlands)

    P.K. Jha

    2016-01-01

    The mammalian master pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN generates rhythms of behavioural and metabolic processes throughout the body via both endocrine and neuronal outputs. For example, daily rhythms of sleep-wake, fasting-feeding, plasma glucose, glucos

  9. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes

    NARCIS (Netherlands)

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rahbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Background: This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. Material and methods: To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated

  10. Insulin resistance for glucose metabolism in disused soleus muscle of mice

    Science.gov (United States)

    Seider, M. J.; Nicholson, W. F.; Booth, F. W.

    1981-01-01

    Results of this study on mice provide the first direct evidence of insulin resistance for glucose metabolism in skeletal muscle that has undergone a previous period of reduced muscle usage. This lack of responsiveness to insulin developed in one day and in the presence of hypoinsulinemia. Future studies will utilize the model of hindlimb immobilization to determine the causes of these changes.

  11. Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: a controlled positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Otte, A. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland)]|[Department of Nuclear Medicine, University Hospital Freiburg (Germany); Weiner, S.M. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Peter, H.H. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Mueller-Brand, J. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland); Goetze, M. [Institute of Nuclear Medicine, University Hospital, Basel (Switzerland); Moser, E. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Gutfleisch, J. [Department of Rheumatology and Immunology, University Hospital Freiburg (Germany); Hoegerle, S. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Juengling, F.D. [Department of Nuclear Medicine, University Hospital Freiburg (Germany); Nitzsche, E.U. [Department of Nuclear Medicine, University Hospital Freiburg (Germany)

    1997-07-01

    In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40{+-}14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40{+-}12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922{+-}0.045 in patients and 1.066{+-}0.081 in controls (P<0.0001, Mann Whitney U test), while on the left side it was 0.892{+-}0.060 in patients and 1.034{+-}0.051 in controls (P=0.0002). Parieto-occipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular disease. (orig.). With 1 fig., 1 tab.

  12. Strategies for improving the Voxel-based statistical analysis for animal PET studies: assessment of cerebral glucose metabolism in cat deafness model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Lee, Jae Sung; Park, Min Hyun; Kang, Hye Jin; Im, Ki Chun; Moon, Dae Hyuk; Lim, Sang Moo; Oh, Seung Ha; Lee, Dong Soo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In imaging studies of the human brain, voxel-based statistical analysis method was widely used, since these methods were originally developed for the analysis of the human brain data, they are not optimal for the animal brain data. The aim of this study is to optimize the procedures for the 3D voxel-based statistical analysis of cat FDG PET brain images. A microPET Focus 120 scanner was used. Eight cats underwent FDG PET scans twice before and after inducing the deafness. Only the brain and adjacent regions were extracted from each data set by manual masking. Individual PET image at normal and deaf state was realigned to each other to remove the confounding effects by the different spatial normalization parameters on the results of statistical analyses. Distance between the sampling points on the reference image and kernel size of Gaussian filter applied to the images before estimating the realignment parameters were adjusted to 0.5 mm and 2 mm. Both data was then spatial normalized onto study-specific cat brain template. Spatially normalized PET data were smoothed and voxel-based paired t-test was performed. Cerebral glucose metabolism decreased significantly after the loss of hearing capability in parietal lobes, postcentral gyri, STG, MTG, lTG, and IC at both hemisphere and left SC (FDR corrected P < 0.05, k=50). Cerebral glucose metabolism in deaf cats was found to be significantly higher than in controls in the right cingulate (FDR corrected P < 0.05, k=50). The ROI analysis also showed significant reduction of glucose metabolism in the same areas as in the SPM analysis, except for some regions (P < 0.05). Method for the voxel-based analysis of cat brain PET data was optimized for analysis of cat brain PET. This result was also confirmed by ROI analysis. The results obtained demonstrated the high localization accuracy and specificity of the developed method, and were found to be useful for examining cerebral glucose metabolism in a cat cortical deafness model.

  13. Effects of Reductions of Body Fat and Regional Adipose Tissue on Glucose and Lipid Metabolism Among Eldery Japanese

    OpenAIRE

    Shigeto, Kazuhiro; Koyama, Hiroshi; Takemoto, Tai-ichiro

    1989-01-01

    To evaluate effects of improvement of obesity on glucose and lipid metabolism, changes of body weight, skinfolds and biochemical parameters in glucose and lipid metabolism were examined through a six month health education on excercise and diet. Subjects were 20 men and 36 women aged from 48 to 87, who had overweight and/or glucose intolerance. Weight, relative weight and fat mass were significantly reduced after the program in both sexes. Circumference ratios were reduced only in women. The ...

  14. Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

    OpenAIRE

    Frederick Wasinski; Gregnani, Marcos F.; Ornellas, Fábio H.; Aline V N Bacurau; Câmara, Niels O.; Ronaldo C Araujo; Reury F. Bacurau

    2014-01-01

    Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight ...

  15. Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women.

    Science.gov (United States)

    Boirie, Y; Gachon, P; Cordat, N; Ritz, P; Beaufrère, B

    2001-02-01

    Regulation of glucose homeostasis by insulin is modified during aging, but whether this alteration is associated with changes in protein metabolism is less defined. Insulin dose responses of whole body glucose, leucine, and albumin metabolism have been investigated using isotopic dilution of D-[6, 6-(2)H(2)]glucose and L-[1-(13)C]leucine in 14 young (Y; 24.0 +/- 0.9 yr; mean +/- SEM, 20.5 +/- 0.4 kg/m(2)) and 12 healthy elderly subjects (E; 69.4 +/- 0.6 yr; 24.6 +/- 0.8 kg/m(2)) using a euglycemic and euaminoacidemic hyperinsulinemic clamp at two insulin infusion rates of 0.2 and 0.5 mU/kg.min (CL1 and CL2, respectively). Despite significantly higher plasma insulin in E than in Y, the glucose disposal rate was lower in E than in Y at both insulin levels, whereas glucose production was normally suppressed. Whole body protein breakdown was less inhibited by insulin in E than in Y at CL1 (-13.5 +/- 1.4% vs. -8.8 +/- 1.3%, Y vs. E, P CL2 (-22.0 +/- 1.4% vs. -18.8 +/- 1.7%, Y vs. E, P = NS). The albumin synthesis rate was identical and stimulated to the same extent by insulin in groups Y and E. Gender affected basal leucine metabolism, but the response to insulin was similar in both groups. In conclusion, decreased insulin action on glucose disposal is associated with a reduced insulin sensitivity for protein breakdown in healthy elderly subjects at low insulin concentrations. Higher insulin levels compensate for a reduced insulin action on protein metabolism in elderly subjects. PMID:11158022

  16. End products of glucose and glutamine metabolism by L929 cells.

    Science.gov (United States)

    Lanks, K W

    1987-07-25

    Products of glucose and glutamine metabolism by L929 cells were detected and quantitated by gas chromatography and mass spectrometry of the oxime-trimethylsilyl derivatives. This method allowed detection and identification of all major carboxylic and amino acids produced in the system. Although lactic acid was expected to be the major product, alanine, citric, glutamic, aspartic, and pyruvic acids were also released into the culture medium at significant rates. Incorporation of labeled carbon from D-[U-13C]glucose showed that the alanine, lactic, and pyruvic acids were derived from glucose as was one-third of the citric acid carbon. The rate of glucose utilization for production of these end products was 29-fold greater than the rate of glucose oxidation to CO2, and calculated ATP production from alanine and pyruvate synthesis exceeded that from lactate synthesis by nearly 2-fold. Utilization of glutamine for synthesis of aspartic, glutamic, and citric acids also exceeded the rate of glutamine oxidation, thereby making end-product synthesis from glucose and glutamine the dominant cellular metabolic activity. In the absence of glucose, synthesis and intracellular levels of aspartic and glutamic acids increased, whereas synthesis and cell content of the other acids decreased markedly. This response is consistent with the metabolic pattern proposed by Moreadith and Lehninger (Moreadith, R.W., and Lehninger, A.L. (1984) J. Biol. Chem. 259, 6215-6221) in which much of the glutamine used by these cells is converted to aspartate in the absence of a pyruvate source and to aspartate or citrate in the presence of pyruvate. PMID:3611053

  17. Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp ATCC 39727

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Bruheim, Per; Nielsen, Jens

    2004-01-01

    The actinomycete Nonomuraea sp. ATCC 39727, producer of the glycopeptide A40926 that is used as precursor for the novel antibiotic dalbavancin, has an unusual carbon metabolism. Glucose is primarily metabolized via the Entner-Doudoroff (ED) pathway, although the energetically more favorable Embden...... - Meyerhof - Parnas (EMP) pathway is present in this organism. Moreover, Nonomuraea utilizes a PPi-dependent phosphofructokinase, an enzyme that has been connected with anaerobic metabolism in eukaryotes and higher plants, but recently has been recognized in several actinomycetes. In order to study its...

  18. Similarities of cerebral glucose metabolism in Alzheimer's and Parkinsonian dementia

    International Nuclear Information System (INIS)

    In the dementia of probable Alzheimer's Disease (AD), there is a decrease in the metabolic ratio of parietal cortex/caudate-thalamus which relates measures in the most and in the least severely affected locations. Since some demented patients with Parkinson's Disease (PDD) are known to share pathological and neurochemical features with AD patients, the authors evaluated if the distribution of cerebral hypometabolism in PDD and AD were the same. Local cerebral metabolic rates were determined using the FDG method and positron tomography in subjects with AD (N=23), and PDD (N=7), multiple infarct dementia (MID)(N=6), and controls (N=10). In MID, the mean par/caudthal ratio was normal (0.79 +- 0.9, N=6). In AD and PDD patients, this ratio correlated negatively with both the severity (r=-0.624, rho=0.001) and duration (r=-0.657, rho=0.001) of dementia. The ratio was markedly decreased in subjects with mild to severe dementia (0.46 +- 0.09, N=21) and with dementia duration greater than two years (0.44 +- 0.08, N=18), but the ratio was also significantly decreased in patients with less advanced disease, i.e., when dementia was only questionable (0.64 +- 0.14, N=9) (t=2.27, rho<0.037) and when duration was two years or less (0.62 +- 0.13, N=12)(t=2.88, rho<0.009). This similarity of hypometabolism in AD and PDD is additional evidence that a common mechanism may operate in both disorders. The par/caud-thal metabolic ratio may be an index useful in the differential diagnosis of early dementia

  19. Clinical significance of determination of serum leptin, insulin levels and blood sugar in pregnant women with glucose metabolism disturbances

    International Nuclear Information System (INIS)

    Objective: To investigate the changes of serum leptin, insulin levels and blood sugar contents in pregnant women with gestational glucose metabolism disturbances. Methods: Fasting and 3h after oral 50g glucose serum levels of leptin were measured with RIA in 36 pregnant women with glucose metabolism disturbances (gestational diabetes mellitus or gestational impaired glucose tolerance) and 34 controls. Also, fasting serum insulin levels (with CLIA) and blood sugar contents 1h after oral 50 glucose (with glucose oxidase method) were determined in all these subjects. Results: 1. Serum levels of leptin in pregnant women with glucose metabolism disturbances were 14.9 ± 4.3 μg/L (vs controls 9.8 ± 1.7 μg/L, P<0.01). 2. The serum levels of insulin and 1 h post - 50g glucose blood sugar contents in pregnant women with glucose metabolism disturbances were 12.9±4.3mU/L and 11.0±1.4mmol/L respectively, which were both significantly positively correlated with the serum leptin levels (r=0.835, r=0.758 respectively) (vs levels in controls: 8.45±3.0mU/L and 7.84±1.3mmol/L). Conclusion: Elevation of fasting serum levels of leptin was demonstrated in pregnant women with glucose metabolism disturbances and the level of leptin was positively correlated with that of insulin and blood sugar. (authors)

  20. Regional difference of glucose metabolism reduction in equivocal Alzheimer's disease and elderly depressed patients

    Energy Technology Data Exchange (ETDEWEB)

    Cho, S. S.; Kang, E. J.; Lee, J. S.; Lee, D. S.; Lee, K. U.; Chung, J. K.; Woo, J. I.; Lee, M. C. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2001-07-01

    The aim of this study was to investigate the difference in cerebral glucose metabolism between patients with equivocal Alzheimer's disease (eAD) and those with elderly major depression (DEP). 31 patients with eAD, 7 patients with DEP, and 15 age matched normal controls were scanned with FDG-PET. Each FDG-PET images was normalized to the cerebellar activity before voxel-voxel analysis using SPM99. In comparison with normal controls, the eAD patents showed the most significant reduction of glucose metabolism (hypometabolism) in anterior inferior temporal gyrus in left, followed by bilateral posterior cingulate, left thalamus, and inferior parietal lobe. Patients with DEP showed hypometabolism in precuneus, inferior and middle frontal gyri in left, and right angular gyrus. Significantly lower activity was found in left inferior temporal gyrus in DEP in comparison to the eAD. Patients with eAD and DEP showed different pattern of hypometabolism, especially in inferior temporal gyrus. FDG brain PET may be useful in differential diagnosis between equivocal Alzheimer's disease and elderly depression.

  1. Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes.

    Science.gov (United States)

    Kocbuch, Katarzyna; Sakowicz-Burkiewicz, Monika; Grden, Marzena; Szutowicz, Andrzej; Pawelczyk, Tadeusz

    2009-01-01

    In diabetes several aspects of immunity are altered, including the immunomodulatory action of adenosine. Our study was undertaken to investigate the effect of different glucose and insulin concentrations on activities of adenosine metabolizing enzymes in human B lymphocytes line SKW 6.4. The activity of adenosine deaminase in the cytosolic fraction was very low and was not affected by different glucose concentration, but in the membrane fraction of cells cultured with 25 mM glucose it was decreased by about 35% comparing to the activity in cells maintained in 5 mM glucose, irrespective of insulin concentration. The activities of 5'-nucleotidase (5'-NT) and ecto-5'-NT in SKW 6.4 cells depended on insulin concentration, but not on glucose. Cells cultured with 10(-8) M insulin displayed an about 60% lower activity of cytosolic 5'-NT comparing to cells maintained at 10(-11) M insulin. The activity of ecto-5'-NT was decreased by about 70% in cells cultured with 10(-8) M insulin comparing to cells grown in 10(-11) M insulin. Neither insulin nor glucose had an effect on adenosine kinase (AK) activity in SKW 6.4 cells or in human B cells isolated from peripheral blood. The extracellular level of adenosine and inosine during accelerated catabolism of cellular ATP depended on glucose, but not on insulin concentration. Concluding, our study demonstrates that glucose and insulin differentially affect the activities of adenosine metabolizing enzymes in human B lymphocytes, but changes in those activities do not correlate with the adenosine level in cell media during accelerated ATP catabolism, implying that nucleoside transport is the primary factor determining the extracellular level of adenosine.

  2. Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice.

    Directory of Open Access Journals (Sweden)

    Jingbo Pang

    Full Text Available Obesity and type 2 diabetes are associated with increased production of Galectin-3 (Gal-3, a protein that modulates inflammation and clearance of glucose adducts. We used Lean and Diet-induced Obese (DIO WT and Gal-3 KO mice to investigate the role of Gal-3 in modulation of adiposity, glucose metabolism and inflammation. Deficiency of Gal-3 lead to age-dependent development of excess adiposity and systemic inflammation, as indicated by elevated production of acute-phase proteins, number of circulating pro-inflammatory Ly6C(high monocytes and development of neutrophilia, microcytic anemia and thrombocytosis in 20-week-old Lean and DIO male Gal-3 KO mice. This was associated with impaired fasting glucose, heightened response to a glucose tolerance test and reduced adipose tissue expression of adiponectin, Gal-12, ATGL and PPARγ, in the presence of maintained insulin sensitivity and hepatic expression of gluconeogenic enzymes in 20-week-old Gal-3 KO mice compared to their diet-matched WT controls. Expression of PGC-1α and FGF-21 in the liver of Lean Gal-3 KO mice was comparable to that observed in DIO animals. Impaired fasting glucose and altered responsiveness to a glucose load preceded development of excess adiposity and systemic inflammation, as demonstrated in 12-week-old Gal-3 KO mice. Finally, a role for the microflora in mediating the fasting hyperglycemia, but not the excessive response to a glucose load, of 12-week-old Gal-3 KO mice was demonstrated by administration of antibiotics. In conclusion, Gal-3 is an important modulator of glucose metabolism, adiposity and inflammation.

  3. Validation of Parkinsonian Disease-Related Metabolic Brain Patterns

    NARCIS (Netherlands)

    Teune, Laura K.; Renken, Remco J.; Mudali, Deborah; De Jong, Bauke M.; Dierckx, Rudi A.; Roerdink, Jos B.T.M.; Leenders, Klaus L.

    2013-01-01

    Background: The objective of this study was to validate disease-related metabolic brain patterns for Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Methods: The study included 20 patients with Parkinson’s disease, 21 with multiple system atrophy, and 17 with progre

  4. Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Makoto; Ichiya, Yuici; Kuwabara, Yasuo (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine) (and others)

    1989-11-01

    Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author).

  5. Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

    International Nuclear Information System (INIS)

    Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author)

  6. Deoxyglucose method for the estimation of local myocardial glucose metabolism with positron computed tomography

    International Nuclear Information System (INIS)

    The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to studies of the heart with positron computed tomography (PCT) and FDG. Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by direct arterial-venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was elevated 5 times the control value or when metabolism was reduced to 10% of normal and MBF increased 5 times normal. Improvements in PCT resolution are required to improve the accuracy of the estimates of the rate constants and the MMRGlc

  7. Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

    Science.gov (United States)

    Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

    2011-01-01

    Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

  8. Depression, anxiety and glucose metabolism in the general dutch population: the new Hoorn study.

    Directory of Open Access Journals (Sweden)

    Vanessa Bouwman

    Full Text Available BACKGROUND: There is a well recognized association between depression and diabetes. However, there is little empirical data about the prevalence of depressive symptoms and anxiety among different groups of glucose metabolism in population based samples. The aim of this study was to determine whether the prevalence of increased levels of depression and anxiety is different between patients with type 2 diabetes and subjects with impaired glucose metabolism (IGM and normal glucose metabolism (NGM. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional data from a population-based cohort study of 2667 residents, 1261 men and 1406 women aged 40-65 years from the Hoorn region, the Netherlands. Depressive symptoms and anxiety were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D, score >or=16 and the Hospital Anxiety and Depression Scale--Anxiety Subscale (HADS-A, score >or=8, respectively. Glucose metabolism status was determined by oral glucose tolerance test. In the total study population the prevalence of depressive symptoms and anxiety for the NGM, IGM and type 2 diabetes were 12.5, 12.2 and 21.0% (P = 0.004 and 15.0, 15.3 and 19.9% (p = 0.216, respectively. In men, the prevalence of depressive symptoms was 7.7, 9.5 and 19.6% (p<0.001, and in women 16.4, 15.8 and 22.6 (p = 0.318, for participants with NGM, IGM and type 2 diabetes, respectively. Anxiety was not associated with glucose metabolism when stratified for sex. Intergroup differences (NGM vs. IGM and IGM vs. type 2 diabetes revealed that higher prevalences of depressive symptoms are mainly manifested in participants with type 2 diabetes, and not in participants with IGM. CONCLUSIONS: Depressive symptoms, but not anxiety are associated with glucose metabolism. This association is mainly determined by a higher prevalence of depressive symptoms in participants with type 2 diabetes and not in participants with IGM.

  9. The metabolic syndrome: a brain disease?

    Science.gov (United States)

    Buijs, Ruud M; Kreier, Felix

    2006-09-01

    The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia--the metabolic syndrome--is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each morning for the coming activity period is altered due to a modern life style of low activity during the day and late-night food intake. Furthermore, we review the anatomical evidence supporting the proposal that an unbalanced autonomic nervous system output may lead to the simultaneous occurrence of diabetes type 2, dyslipidemia, hypertension and visceral obesity.

  10. Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

    Directory of Open Access Journals (Sweden)

    Maxi Meissner

    Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

  11. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    Energy Technology Data Exchange (ETDEWEB)

    Bass, V. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Gordon, C.J.; Jarema, K.A.; MacPhail, R.C. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Cascio, W.E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Phillips, P.M. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Ledbetter, A.D.; Schladweiler, M.C. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Andrews, D. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Miller, D. [Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC (United States); Doerfler, D.L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, U.P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2013-12-15

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone

  12. Modulation of (14) C-labeled glucose metabolism by zinc during aluminium induced neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2015-09-01

    Aluminium (Al) is one of the most prominent metals in the environment and is responsible for causing several neurological disorders, including Alzheimer's disease. On the other hand, zinc (Zn) is an essential micronutrient that is involved in regulating brain development and function. The present study investigates the protective potential of Zn in the uptake of (14) C-labeled amino acids and glucose and their turnover in rat brain slices during Al intoxication. Male Sprague Dawley rats (140-160 g) were divided into four different groups: normal control, Al treated (100 mg/kg body weight/day via oral gavage), Zn treated (227 mg/liter in drinking water), and Al + Zn treated. Radiorespirometric assay revealed an increase in glucose turnover after Al exposure that was attenuated after Zn treatment. Furthermore, the uptake of (14) C-labeled glucose was increased after Al treatment but was appreciably decreased upon Zn supplementation. In addition, the uptakes of (14) C-lysine, (14) C-leucine, and (14) C-aspartic acid were also found to be elevated following Al exposure but were decreased after Zn treatment. Al treatment also caused alterations in the neurohistoarchitecture of the brain, which were improved after Zn coadministration. Therefore, the present study suggests that Zn provides protection against Al-induced neurotoxicity by regulating glucose and amino acid uptake in rats, indicating that Zn could be a potential candidate for the treatment of various neurodegenerative disorders.

  13. Modulation of (14) C-labeled glucose metabolism by zinc during aluminium induced neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2015-09-01

    Aluminium (Al) is one of the most prominent metals in the environment and is responsible for causing several neurological disorders, including Alzheimer's disease. On the other hand, zinc (Zn) is an essential micronutrient that is involved in regulating brain development and function. The present study investigates the protective potential of Zn in the uptake of (14) C-labeled amino acids and glucose and their turnover in rat brain slices during Al intoxication. Male Sprague Dawley rats (140-160 g) were divided into four different groups: normal control, Al treated (100 mg/kg body weight/day via oral gavage), Zn treated (227 mg/liter in drinking water), and Al + Zn treated. Radiorespirometric assay revealed an increase in glucose turnover after Al exposure that was attenuated after Zn treatment. Furthermore, the uptake of (14) C-labeled glucose was increased after Al treatment but was appreciably decreased upon Zn supplementation. In addition, the uptakes of (14) C-lysine, (14) C-leucine, and (14) C-aspartic acid were also found to be elevated following Al exposure but were decreased after Zn treatment. Al treatment also caused alterations in the neurohistoarchitecture of the brain, which were improved after Zn coadministration. Therefore, the present study suggests that Zn provides protection against Al-induced neurotoxicity by regulating glucose and amino acid uptake in rats, indicating that Zn could be a potential candidate for the treatment of various neurodegenerative disorders. PMID:25908409

  14. Aerobic glucose metabolism of Saccharomyces kluyveri: Growth, metabolite production, and quantification of metabolic fluxes

    DEFF Research Database (Denmark)

    Møller, Kasper; Christensen, B.; Förster, Jochen;

    2002-01-01

    growth in aerobic glucose-limited continuous cultivation. It was found that in S. kluyveri the flux into the pentose phosphate pathway was 18.8 mmole per 100 mmole glucose consumed during respiratory growth in aerobic glucose-limited continuous cultivation. Such a low flux into the pentose phosphate...... pathway cannot provide the cell with enough NADPH for biomass formation which is why the remaining NADPH will have to be provided by another pathway. During batch cultivation of S. kluyveri the tricarboxylic acid cycle was working as a cycle with a considerable flux, that is in sharp contrast to what has...

  15. Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro

    Institute of Scientific and Technical Information of China (English)

    Rong ZHOU; Ling WANG; Xing XU; Jing CHEN; Li-hong HU; Li-li CHEN; Xu SHEN

    2013-01-01

    Aim:To discover the active compound on AMP-activated protein kinase (AMPK) activation and investigate the effects of the active compound 1,8-dihydroxyanthraquinone (danthron) from the traditional Chinese medicine rhubarb on AMPK-mediated lipid and glucose metabolism in vitro.Methods:HepG2 and C2C12 cells were used.Cell viability was determined using MTT assay.Real-time PCR was performed to measure the gene expression.Western blotting assay was applied to investigate the protein phosphorylation level.Enzymatic assay kits were used to detect the total cholesterol (TC),triglyceride (TG) and glucose contents.Results:Danthron (0.1,1,and 10 μmol/L) dose-dependently promoted the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC)in both HepG2 and C2C12 cells.Meanwhile,danthron treatment significantly reduced the lipid synthesis related sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthetase (FAS) gene expressions,and the TC and TG levels.In addition,danthron treatment efficiently increased glucose consumption.The actions of danthron on lipid and glucose metabolism were abolished or reversed by co-treatment with the AMPK inhibitor compound C.Conclusion:Danthron effectively reduces intracellular lipid contents and enhanced glucose consumption in vitro via activation of AMPK signaling pathway.

  16. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Wagner, Anika E; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-10-13

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies.

  17. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Domenico Tricò

    2016-01-01

    Full Text Available Dilated cardiomyopathy (DCM is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT. In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT and 5 with AGT (DCM-AGT, and 5 non-DCM subjects with AGT (N-AGT, we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min, and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p<0.05, did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p<0.05, while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

  18. Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

    Science.gov (United States)

    Stanley, W C; Hall, J L; Smith, K R; Cartee, G D; Hacker, T A; Wisneski, J A

    1994-01-01

    We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Varma

    2015-06-01

    Full Text Available Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001. However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes.

  20. Diabetes, glucose metabolism, and glaucoma: the 2005-2008 National Health and Nutrition Examination Survey.

    Directory of Open Access Journals (Sweden)

    Di Zhao

    Full Text Available BACKGROUND: Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples. OBJECTIVE: To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the general U.S. population. METHODS: Cross-sectional study of 3,299 adult men and women from the 2005-2008 National Health and NutritionExamination Survey (NHANES. The presence of diabetes, prediabetes, the metabolic syndrome and its individual components and biomarkers of glucose metabolisms were based on standardized questionnaire and physical exam data and laboratory tests. The history of glaucoma was assessed through questionnaire during the home interview. RESULTS: Diabetes was strongly associated with prevalent glaucoma.In fully adjusted models, the odds ratiofor glaucoma comparing participants with diabetes with participants in the reference group with neither pre-diabetes nor diabetes was 2.12 (95% CI: 1.23, 3.67. The corresponding odd ratio comparing participants with pre-diabetes to those in the reference group was 1.01 (95% CI: 0.57, 1.82. Patients with 5 or more years of diabetes duration hadan OR for glaucoma of 3.90 (95% CI: 1.63, 9.32 compared with patients with <5 years of diabetes duration. We also found a hockey-stick shaped associations between biomarkers of glucose metabolisms and the prevalence of glaucoma. CONCLUSIONS: Diabetes was associated with higher risk of glaucoma. Participants without diabetes but at the higher levels of fasting glucose, fasting insulin, HbA1c and HOMA-IR spectrum may also be at greater risk of glaucoma.

  1. Diabetes, Glucose Metabolism, and Glaucoma: The 2005–2008 National Health and Nutrition Examination Survey

    Science.gov (United States)

    Zhao, Di; Cho, Juhee; Kim, Myung Hun; Friedman, David; Guallar, Eliseo

    2014-01-01

    Background Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples. Objective To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the general U.S. population. Methods Cross-sectional study of 3,299 adult men and women from the 2005–2008 National Health and NutritionExamination Survey (NHANES). The presence of diabetes, prediabetes, the metabolic syndrome and its individual components and biomarkers of glucose metabolisms were based on standardized questionnaire and physical exam data and laboratory tests. The history of glaucoma was assessed through questionnaire during the home interview. Results Diabetes was strongly associated with prevalent glaucoma.In fully adjusted models, the odds ratiofor glaucoma comparing participants with diabetes with participants in the reference group with neither pre-diabetes nor diabetes was 2.12 (95% CI: 1.23, 3.67). The corresponding odd ratio comparing participants with pre-diabetes to those in the reference group was 1.01 (95% CI: 0.57, 1.82). Patients with 5 or more years of diabetes duration hadan OR for glaucoma of 3.90 (95% CI: 1.63, 9.32) compared with patients with <5 years of diabetes duration. We also found a hockey-stick shaped associations between biomarkers of glucose metabolisms and the prevalence of glaucoma. Conclusions Diabetes was associated with higher risk of glaucoma. Participants without diabetes but at the higher levels of fasting glucose, fasting insulin, HbA1c and HOMA-IR spectrum may also be at greater risk of glaucoma. PMID:25393836

  2. Effect of peripheral 5-HT on glucose and lipid metabolism in wether sheep.

    Directory of Open Access Journals (Sweden)

    Hitoshi Watanabe

    Full Text Available In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species.

  3. Hormone and glucose metabolic effects of compound cyproterone acetate in women with polycystic ovarian syndrome

    International Nuclear Information System (INIS)

    To investigate the clinical efficacy of compound cyproterone acetate(CPY) in the treatment of polycystic ovarian syndrome(PCOS) and study hormone and glucose metabolic effects, thirty-five PCOS patients were treated by compound cyproterone acetate for 3 cycles. The serum LH, FSH and T levels, fasting glucose and fasting insulin were determined before and after 3 cycle's treatment. The results showed that 34 patients had regular menses during CPY therapy. The hirsute and acne score decreased significantly(P0.05). The results indicate that the compound cyproterone acetate had anti-androgenic effects on PCOS patients and improved their endocrine function and clinical syndrome. (authors)

  4. Cereal Processing Influences Postprandial Glucose Metabolism as Well as the GI Effect

    OpenAIRE

    Vinoy, Sophie; Normand, Sylvie; Meynier, Alexandra; Sothier, Monique; Louche-Pelissier, Corinne; Peyrat, Jocelyne; Maitrepierre, Christine; Nazare, Julie-Anne; Brand-Miller, Jeannie; Laville, Martine

    2015-01-01

    Objective: Technological processes may influence the release of glucose in starch. The aim of this study was to compare the metabolic response and the kinetics of appearance of exogenous glucose from 2 cereal products consumed at breakfast. Methods: Twenty-five healthy men were submitted to a randomized, open, crossover study that was divided into 2 parts: 12 of the 25 subjects were included in the “isotope part,” and the 13 other subjects were included in the “glycemic part.” On test days, s...

  5. Effect of abomasal glucose infusion on splanchnic amino acid metabolism in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic AA metabolism. The experimental design was a split plot, with cow as the whole...... plot, treatment as the whole-plot factor and days in milk (DIM) as the subplot factor. Cows were assigned to 1 of 2 treatments: control or infusion of 1,500 g/d of glucose into the abomasum from the day of calving to 29 DIM....

  6. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain;

    2015-01-01

    with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean...... with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. clinicaltrials.gov NCT01633762....

  7. Glutamatergic and GABAergic energy metabolism measured in the rat brain by (13) C NMR spectroscopy at 14.1 T.

    Science.gov (United States)

    Duarte, João M N; Gruetter, Rolf

    2013-09-01

    Energy metabolism supports both inhibitory and excitatory neurotransmission processes. This study investigated the specific contribution of astrocytic metabolism to γ-aminobutyric acid (GABA) synthesis and inhibitory GABAergic neurotransmission that remained to be ilucidated in vivo. Therefore, we measured (13)C incorporation into brain metabolites by dynamic (13)C nuclear magnetic resonance spectroscopy at 14.1 T in rats under α-chloralose anaesthesia during infusion of [1,6-(13)C]glucose. The enhanced sensitivity at 14.1 T allowed to quantify incorporation of (13) C into the three aliphatic carbons of GABA non-invasively. Metabolic fluxes were determined with a mathematical model of brain metabolism comprising glial, glutamatergic and GABAergic compartments. GABA synthesis rate was 0.11 ± 0.01 μmol/g/min. GABA-glutamine cycle was 0.053 ± 0.003 μmol/g/min and accounted for 22 ± 1% of total neurotransmitter cycling between neurons and glia. Cerebral glucose oxidation was 0.47 ± 0.02 μmol/g/min, of which 35 ± 1% and 7 ± 1% was diverted to the glutamatergic and GABAergic tricarboxylic acid cycles, respectively. The remaining fraction of glucose oxidation was in glia, where 12 ± 1% of the TCA cycle flux was dedicated to oxidation of GABA. 16 ± 2% of glutamine synthesis was provided to GABAergic neurons. We conclude that substantial metabolic activity occurs in GABAergic neurons and that glial metabolism supports both glutamatergic and GABAergic neurons in the living rat brain. PMID:23745684

  8. TAp63 is a master transcriptional regulator of lipid and glucose metabolism

    Science.gov (United States)

    Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y.; Flores, Elsa R.

    2012-01-01

    SUMMARY TAp63 prevents premature aging suggesting a link to genes that regulate longevity. Further characterization of TAp63−/− mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance, similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulating energy metabolism by accumulating in response to metabolic stress and transcriptionally activating Sirt1, AMPKα2, and LKB1 resulting in increased fatty acid synthesis and decreased fatty acid oxidation. Moreover, we found that TAp63 lowers blood glucose levels in response to metformin. Restoration of Sirt1, AMPKα2, and LKB1 in TAp63−/− mice rescued some of the metabolic defects of the TAp63−/− mice. Our study defines a role for TAp63 in metabolism and weight control. PMID:23040072

  9. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism.

    Science.gov (United States)

    Molehin, Deborah; Dekker Nitert, Marloes; Richard, Kerry

    2016-01-01

    Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

  10. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Deborah Molehin

    2016-01-01

    Full Text Available Background. Thyroid hormones (THs are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers.

  11. Metabolic Characteristics of a Glucose-Utilizing Shewanella oneidensis Strain Grown under Electrode-Respiring Conditions.

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    Gen Nakagawa

    Full Text Available In bioelectrochemical systems, the electrode potential is an important parameter affecting the electron flow between electrodes and microbes and microbial metabolic activities. Here, we investigated the metabolic characteristics of a glucose-utilizing strain of engineered Shewanella oneidensis under electrode-respiring conditions in electrochemical reactors for gaining insight into how metabolic pathways in electrochemically active bacteria are affected by the electrode potential. When an electrochemical reactor was operated with its working electrode poised at +0.4 V (vs. an Ag/AgCl reference electrode, the engineered S. oneidensis strain, carrying a plasmid encoding a sugar permease and glucose kinase of Escherichia coli, generated current by oxidizing glucose to acetate and produced D-lactate as an intermediate metabolite. However, D-lactate accumulation was not observed when the engineered strain was grown with a working electrode poised at 0 V. We also found that transcription of genes involved in pyruvate and D-lactate metabolisms was upregulated at a high electrode potential compared with their transcription at a low electrode potential. These results suggest that the carbon catabolic pathway of S. oneidensis can be modified by controlling the potential of a working electrode in an electrochemical bioreactor.

  12. Visceral adiposity influences glucose and glycogen metabolism in control and hyperlipidic-fed animals

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    Danielle Kaiser de Souza

    2013-04-01

    Full Text Available Introduction: Evidences suggest that fat intake, visceral obesity and intracellular lipids are related to insulin impairment. Objective: The objective of the present paper was correlate visceral obesity and metabolic alterations in control (CTR and hyperlipidic cafeteria diet (CFT fed animals. Methods: After 6 months of diet treatment, liver and muscle of the male rats were utilized to determined glucose uptake and glycogen metabolism after administration of 0.4I U/kg insulin in vivo, and correlate the visceral adiposity to these two parameters. Results: Ample range of physiologic answers to body composition in metabolic profile of the both diets was found. No differences were found in glycemia and triacylglycerol after insulin action in both groups, however CFT group accumulated higher adiposity, mostly visceral fat, and showed lower glycogen content in the liver. We also found an inverse correlation between visceral adiposity and glucose uptake and a decrease of the glycogen synthase active form in the liver. CTR animals demonstrated an inverse correlation between glucose uptake and visceral adiposity in the muscle. Discussion and conclusion: It was observed a variability of metabolic alterations in animals which can be related to degree of accumulation of abdominal adiposity and ingestion of diet fats. Further studies will be required to clarify the reasons for the observed liver alterations in CFT and muscle alterations in CTR animals.

  13. Blast Overpressure Waves Induce Transient Anxiety and Regional Changes in Cerebral Glucose Metabolism and Delayed Hyperarousal in Rats.

    Science.gov (United States)

    Awwad, Hibah O; Gonzalez, Larry P; Tompkins, Paul; Lerner, Megan; Brackett, Daniel J; Awasthi, Vibhudutta; Standifer, Kelly M

    2015-01-01

    Physiological alterations, anxiety, and cognitive disorders are strongly associated with blast-induced traumatic brain injury (blast TBI), and are common symptoms in service personnel exposed to blasts. Since 2006, 25,000-30,000 new TBI cases are diagnosed annually in U.S. Service members; increasing evidence confirms that primary blast exposure causes diffuse axonal injury and is often accompanied by altered behavioral outcomes. Behavioral and acute metabolic effects resulting from blast to the head in the absence of thoracic contributions from the periphery were examined, following a single blast wave directed to the head of male Sprague-Dawley rats protected by a lead shield over the torso. An 80 psi head blast produced cognitive deficits that were detected in working memory. Blast TBI rats displayed increased anxiety as determined by elevated plus maze at day 9 post-blast compared to sham rats; blast TBI rats spent significantly more time than the sham controls in the closed arms (p blast. Instead, blast TBI rats displayed increased rearing behavior at day 48 post-blast compared to sham rats. Blast TBI rats also exhibited suppressed acoustic startle responses, but similar pre-pulse inhibition at day 15 post-blast compared to sham rats. Acute physiological alterations in cerebral glucose metabolism were determined by positron emission tomography 1 and 9 days post-blast using (18)F-fluorodeoxyglucose ((18)F-FDG). Global glucose uptake in blast TBI rat brains increased at day 1 post-blast (p blast injury. Markers for reactive astrogliosis and neuronal damage were noted by immunoblotting motor cortex tissue from day 10 post-blast in blast TBI rats compared to sham controls (p < 0.05; n = 5-6). PMID:26136722

  14. Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.

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    Radka Gromnicova

    Full Text Available The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

  15. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

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    Charlene eDiepenbroek

    2013-12-01

    Full Text Available Deep brain stimulation (DBS of the nucleus accumbens (NAc is an effective therapy for obsessive compulsive disorder (OCD and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of one hour. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients.

  16. Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats.

    Science.gov (United States)

    Diepenbroek, Charlene; van der Plasse, Geoffrey; Eggels, Leslie; Rijnsburger, Merel; Feenstra, Matthijs G P; Kalsbeek, Andries; Denys, Damiaan; Fliers, Eric; Serlie, Mireille J; la Fleur, Susanne E

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients. PMID:24339800

  17. Increased Brain Fatty Acid Uptake in Metabolic Syndrome

    Science.gov (United States)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti; Hirvonen, Jussi; Fielding, Barbara A.; Virtanen, Kirsi; Oikonen, Vesa; Kemppainen, Jukka; Viljanen, Tapio; Guiducci, Letizia; Haaparanta-Solin, Merja; Någren, Kjell; Solin, Olof; Nuutila, Pirjo

    2010-01-01

    OBJECTIVE To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS At baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction. PMID:20566663

  18. Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

    Directory of Open Access Journals (Sweden)

    Muto Takashi

    2011-04-01

    Full Text Available Abstract Background Glycated albumin (GA is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells. Methods Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA and GA was measured under three different glucose concentrations, 3 mM (G3, 7 mM (G7, and 15 mM (G15, with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS, and the expression of iNOS-mRNA was investigated by real-time PCR. Results Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920, and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046, for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion. Conclusion GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.

  19. Effects of bilateral subthalamic nucleus stimulation on resting-state cerebral glucose metabolism in advanced Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    赵永波; 孙伯民; 李殿友; 王乔树

    2004-01-01

    Background The major neuropathological symptoms of Parkinson's disease (PD) consist of a loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. This study was to investigate the effects of bilateral subthalamic nucleus (STN) stimulation on resting-state cerebral glucose metabolism in advanced PD, and investigate the mechanism of deep brain stimulation (DBS).Methods Seven consecutive advanced PD patients (4 men and 3 women, mean age 64±4 years, mean H-Y disability rating 4.4±0.65) receiving bilateral STN DBS underwent 18F-fluorodeoxyglucose (18F-FDG)/positron-emission tomography (PET) examinations at rest both preoperatively and one month postoperatively, with STN stimulation still on. The unified PD rating scale was used to evaluate the clinical state under each condition. Statistical parametric mapping (SPM) was used to investigate the regional cerebral metabolic rates of glucose (rCMRGlu) during STN stimulation, and to compare these values to rCMRGlu preoperation. Results STN stimulation clearly improved clinical symptoms in all patients. A significant increase in rCMRGlu was found in the bilateral lentiform nucleus, brainstem (midbrain and pons), bilateral premotor area (BA6), parietal-occipital cortex, and anterior cingulated cortex, and a marked decrease in rCMRGlu was noted in the left limbic lobe and bilateral inferior frontal cortex (P<0.05). Conclusion Bilateral STN stimulation may activate the projection axon from the STN, improving clinical symptoms in advanced PD patients by improving both ascending and descending pathways from the basal ganglia and increasing the metabolism of higher-order motor control in the frontal cortex.

  20. A metabolic trade-off between phosphate and glucose utilization in Escherichia coli.

    Science.gov (United States)

    Behrends, Volker; Maharjan, Ram P; Ryall, Ben; Feng, Lu; Liu, Bin; Wang, Lei; Bundy, Jacob G; Ferenci, Thomas

    2014-11-01

    Getting the most out of available nutrients is a key challenge that all organisms face. Little is known about how they optimize and balance the simultaneous utilization of multiple elemental resources. We investigated the effects of long-term phosphate limitation on carbon metabolism of the model organism Escherichia coli using chemostat cultures. We profiled metabolic changes in the growth medium over time and found evidence for an increase in fermentative metabolism despite the aerobic conditions. Using full-genome sequencing and competition experiments, we found that fitness under phosphate-limiting conditions was reproducibly increased by a mutation preventing flux through succinate in the tricarboxylic acid cycle. In contrast, these mutations reduced competitive ability under carbon limitation, and thus reveal a conflicting metabolic benefit in the role of the TCA cycle in environments limited by inorganic phosphate and glucose.

  1. Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice.

    Science.gov (United States)

    Otsuka, Tsuyoshi; Kawai, Misato; Togo, Yuki; Goda, Ryosei; Kawase, Takahiro; Matsuo, Haruka; Iwamoto, Ayaka; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

    2014-02-01

    Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Furthermore, photoperiod altered multiple parameters reflective of peripheral metabolism, including the ratio of plasma l-tryptophan to the sum of other large neutral amino acids that compete for transport across the blood-brain barrier, responses of circulating glucose and insulin to glucose load, sucrose intake under restricted feeding condition, and sensitivity of the brain serotonergic system to peripherally administered glucose. These data suggest that the mechanisms underlying SAD involve the brain-peripheral tissue network, and C57BL/6J mice can serve as a powerful tool for investigating the link between seasons and mood. PMID:24485474

  2. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Science.gov (United States)

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  3. Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose

    DEFF Research Database (Denmark)

    Bülow, J; Simonsen, L; Wiggins, D;

    1999-01-01

    The integration of lipid metabolism in the splanchnic bed and in subcutaneous adipose tissue before and after ingestion of a 75 g glucose load was studied by Fick's principle in seven healthy subjects. Six additional subjects were studied during a hyperinsulinemic euglycemic clamp. Release of non......-esterified fatty acids (NEFA) from adipose tissue and splanchnic NEFA extraction followed a similar time-course after oral glucose, and there was a highly significant relationship between adipose tissue NEFA release and splanchnic NEFA uptake. There was no immediate inhibition of splanchnic very low density...... lipoprotein (VLDL)-triacylglycerol (TAG) output when plasma insulin levels increased after glucose. Adipose tissue extraction of VLDL-TAG tended to vary in time in a manner similar to splanchnic VLDL-TAG output and the two were significantly related. The area-under-curves (AUC) for splanchnic extraction...

  4. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice.

    Science.gov (United States)

    De Angelis, Katia; Senador, Danielle D; Mostarda, Cristiano; Irigoyen, Maria C; Morris, Mariana

    2012-04-15

    Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

  5. Effect of antibiotics on gut microbiota, glucose metabolism and bodyweight regulation - a review of the literature

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbaek; Allin, Kristine Højgaard; Knop, Filip Krag

    2016-01-01

    Gut bacteria are involved in a number of host metabolic processes and have been implicated in the development of obesity and type 2 diabetes in humans. Use of antibiotics changes the composition of the gut microbiota and there is accumulating evidence from observational studies for an association...... between exposure to antibiotics and development of obesity and type 2 diabetes. Here we review human studies examining effects of antibiotics on bodyweight regulation and glucose metabolism and discuss whether the observed findings may relate to alterations in the composition and function of the gut...... microbiota....

  6. Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

    Directory of Open Access Journals (Sweden)

    Reiner Jumpertz

    Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

  7. Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2014-05-15

    The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide - a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential. PMID:24629597

  8. Molecular mechanism of hepatitis C virus-induced glucose metabolic disorders

    Directory of Open Access Journals (Sweden)

    Ikuo eShoji

    2012-01-01

    Full Text Available Hepatitis C virus (HCV infection causes not only intrahepatic diseases but also extrahepatic manifestations, including metabolic disorders. Chronic HCV infection is often associated with type 2 diabetes. However, the precise mechanism underlying this association is still unclear. Glucose is transported into hepatocytes via glucose transporter 2 (GLUT2. Hepatocytes play a crucial role in maintaining plasma glucose homeostasis via the gluconeogenic and glycolytic pathways. We have been investigating the molecular mechanism of HCV-related type 2 diabetes using HCV RNA replicon cells and HCV J6/JFH1 system. We found that HCV replication down-regulates cell surface expression of GLUT2 at the transcriptional level. We also found that HCV infection promotes hepatic gluconeogenesis in HCV J6/JFH1-infected Huh-7.5 cells. HCV infection transcriptionally up-regulated the genes for PEPCK and G6Pase, the rate-limiting enzymes for hepatic gluconeogenesis. Gene expression of PEPCK and G6Pase was regulated by the transcription factor forkhead box O1 (FoxO1 in HCV-infected cells. Phosphorylation of FoxO1 at Ser319 was markedly diminished in HCV-infected cells, resulting in increased nuclear accumulation of FoxO1. HCV NS5A protein was directly linked with the FoxO1-dependent increased gluconeogenesis. This paper will discuss the current model of HCV-induced glucose metabolic disorders.

  9. Elevation in Tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells.

    Science.gov (United States)

    Gao, Yuan; Walder, Ken; Sunderland, Terry; Kantham, Lakshmi; Feng, Helen C; Quick, Melissa; Bishara, Natalie; de Silva, Andrea; Augert, Guy; Tenne-Brown, Janette; Collier, Gregory R

    2003-04-01

    Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

  10. The Relationship between Selenoprotein P and Glucose Metabolism in Experimental Studies

    OpenAIRE

    Jinyuan Mao; Weiping Teng

    2013-01-01

    Selenium is an essential trace element in the diet of mammals which is important for many physiological functions. However, a number of epidemiological studies have suggested that high selenium status is a possible risk factor for the development of type 2 diabetes, although they cannot distinguish between cause and effect. Selenoprotein P (Sepp1) is central to selenium homeostasis and widely expressed in the organism. Here we review the interaction between Sepp1 and glucose metabolism with a...

  11. Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle

    OpenAIRE

    Yasuhiko Minokoshi; Chitoku Toda; Shiki Okamoto

    2012-01-01

    Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulation of food intake, energy expenditure, and neuroendocrine function. Several lines of evidences indicate that independent of the anorexic effect, leptin regulates glucose and lipid metabolism in peripheral tissues in rodents and humans. It has been shown that leptin improves the diabetes phenotype in lipodystrophic patients and rodents. Moreover, leptin suppresses the development of severe, progressive impairment o...

  12. Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

    OpenAIRE

    Krak, Nanda; Hoeven, John; Hoekstra, Otto; Twisk, Jos; Wall, Ernst; Lammertsma, A. A.

    2008-01-01

    textabstractObjective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tum...

  13. Insights into the molecular mechanism of glucose metabolism regulation under stress in chicken skeletal muscle tissues

    OpenAIRE

    Liu, Wuyi; Zhao, Jingpeng

    2014-01-01

    As substantial progress has been achieved in modern poultry production with large-scale and intensive feeding and farming in recent years, stress becomes a vital factor affecting chicken growth, development, and production yield, especially the quality and quantity of skeletal muscle mass. The review was aimed to outline and understand the stress-related genetic regulatory mechanism, which significantly affects glucose metabolism regulation in chicken skeletal muscle tissues. Progress in curr...

  14. Influence of creatine supplementation on indicators of glucose metabolism in skeletal muscle of exercised rats

    OpenAIRE

    Michel Barbosa de Araújo; Roberto Carlos Vieira Junior; Leandro Pereira de Moura; Marcelo Costa Junior; Rodrigo Augusto Dalia; Amanda Christine da Silva Sponton; Carla Ribeiro; Maria Alice Rostom de Mello

    2013-01-01

    The purpose of this study was to evaluate the effect of creatine supplementation in the diet on indicators of glucose metabolism in skeletal muscle of exercised rats. Forty Wistar adult rats were distributed into four groups for eight weeks: 1) Control: sedentary rats that received balanced diet; 2) Creatine control: sedentary rats that received supplementation of 2% creatine in the balanced diet; 3) Trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received balanc...

  15. Zonation of glucose and fatty acid metabolism in the liver : Mechanism and metabolic consequences

    NARCIS (Netherlands)

    Hijmans, Brenda S.; Greffiorst, Aldo; Oosterveer, Maaike H.; Groen, Albert K.

    2014-01-01

    The liver is generally considered as a relatively homogeneous organ containing four different cell types. It is however well-known that the liver is not homogeneous and consists of clearly demarcated metabolic zones. Hepatocytes from different zones show phenotypical heterogeneity in metabolic featu

  16. Expensive brains: ‘brainy’ rodents have higher metabolic rate

    Directory of Open Access Journals (Sweden)

    Raúl eSobrero

    2011-07-01

    Full Text Available Brains are the centers of the nervous system of animals, controlling the organ systems of the body and coordinating responses to changes in the ecological and social environment. The evolution traits that correlate with cognitive ability, such as relative brain size is thus of broad interest. Brain mass relative to body mass varies among mammals, and diverse factors have been proposed to explain this variation. A recent study provided evidence that energetics play an important role in brain evolution (Isler and van Schaik, 2006. Using composite phylogenies and data drawn from multiple sources, these authors showed that basal metabolic rate (BMR correlates with brain mass across mammals. However, no such relationship was found within rodents. Here we re-examined the relationship between BMR and brain mass within Rodentia using a novel species-level phylogeny. Our results are sensitive to parameter evaluation; in particular how species mass is estimated. We detect no pattern when applying an approach used by previous studies, where each species body mass is represented by two different numbers, one being the individual that happened to be used for BMR estimates of that species. However, this approach may compromise the analysis. When using a single value of body mass for each species, whether representing a single individual, or available species mean, our findings provide evidence that brain mass (independent of body mass and BMR are correlated. These findings are thus consistent with the hypothesis that large brains evolve when the payoff for increased brain mass is greater than the energetic cost they incur.

  17. Effects of over-expressing resistin on glucose and lipid metabolism in mice

    Institute of Scientific and Technical Information of China (English)

    You LIU; Qun WANG; Ying-bin PAN; Zhi-jie GAO; Yan-fen LIU; Shao-hong CHEN

    2008-01-01

    Resistin, a newly discovered peptide hormone mainly secreted by adipose tissues, is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However, some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans, no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study, we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection, serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice, both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control, whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore, lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.

  18. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  19. Glucose metabolic flux distribution of Lactobacillus amylophilus during lactic acid production using kitchen waste saccharified solution.

    Science.gov (United States)

    Liu, Jianguo; Wang, Qunhui; Zou, Hui; Liu, Yingying; Wang, Juan; Gan, Kemin; Xiang, Juan

    2013-11-01

    The (13) C isotope tracer method was used to investigate the glucose metabolic flux distribution and regulation in Lactobacillus amylophilus to improve lactic acid production using kitchen waste saccharified solution (KWSS). The results demonstrate that L. amylophilus is a homofermentative bacterium. In synthetic medium, 60.6% of the glucose entered the Embden-Meyerhof-Parnas (EMP) to produce lactic acid, whereas 36.4% of the glucose entered the pentose phosphate metabolic pathway (HMP). After solid-liquid separation of the KWSS, the addition of Fe(3+) during fermentation enhanced the NADPH production efficiency and increased the NADH content. The flux to the EMP was also effectively increased. Compared with the control (60.6% flux to EMP without Fe(3+) addition), the flux to the EMP with the addition of Fe(3+) (74.3%) increased by 23.8%. In the subsequent pyruvate metabolism, Fe(3+) also increased lactate dehydrogenase activity, and inhibited alcohol dehydrogenase, pyruvate dehydrogenase and pyruvate carboxylase, thereby increasing the lactic acid production to 9.03 g l(-1) , an increase of 8% compared with the control. All other organic acid by-products were lower than in the control. However, the addition of Zn(2+) showed an opposite effect, decreasing the lactic acid production. In conclusion it is feasible and effective means using GC-MS, isotope experiment and MATLAB software to integrate research the metabolic flux distribution of lactic acid bacteria, and the results provide the theoretical foundation for similar metabolic flux distribution. PMID:23489617

  20. Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals

    DEFF Research Database (Denmark)

    Jacobsen, Siv H; Bojsen-Møller, Kirstine N; Dirksen, Carsten;

    2013-01-01

    AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles...

  1. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

    Science.gov (United States)

    Garcia-Carbonell, Ricard; Divakaruni, Ajit S.; Lodi, Alessia; Vicente-Suarez, Ildefonso; Saha, Arindam; Cheroutre, Hilde; Boss, Gerry R.; Tiziani, Stefano; Murphy, Anne N.; Guma, Monica

    2016-01-01

    Objective Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. Methods Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-D-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. Results Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo

  2. Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Görs, S; Röntgen, M; Sauerwein, H; Bruckmaier, R M; Metges, C C; Kuhla, B; Hammon, H M

    2016-08-01

    Dairy cows undergo significant metabolic and endocrine changes during the transition from pregnancy to lactation, and impaired insulin action influences nutrient partitioning toward the fetus and the mammary gland. Because impaired insulin action during transition is thought to be related to elevated body condition and body fat mobilization, we hypothesized that over-conditioned cows with excessive body fat mobilization around calving may have impaired insulin metabolism compared with cows with low fat mobilization. Nineteen dairy cows were grouped according to their average concentration of total liver fat (LFC) after calving in low [LLFC; LFC 24.4% total fat/DM; n=10) fat-mobilizing cows. Blood samples were taken from wk 7 antepartum (ap) to wk 5 postpartum (pp) to determine plasma concentrations of glucose, insulin, glucagon, and adiponectin. We applied euglycemic-hyperinsulinemic (EGHIC) and hyperglycemic clamps (HGC) in wk 5 ap and wk 3 pp to measure insulin responsiveness in peripheral tissue and pancreatic insulin secretion during the transition period. Before and during the pp EGHIC, [(13)C6] glucose was infused to determine the rate of glucose appearance (GlucRa) and glucose oxidation (GOx). Body condition, back fat thickness, and energy-corrected milk were greater, but energy balance was lower in HLFC than in LLFC. Plasma concentrations of glucose, insulin, glucagon, and adiponectin decreased at calving, and this was followed by an immediate increase of glucagon and adiponectin after calving. Insulin concentrations ap were higher in HLFC than in LLFC cows, but the EGHIC indicated no differences in peripheral insulin responsiveness among cows ap and pp. However, GlucRa and GOx:GlucRa during the pp EGHIC were greater in HLFC than in LLFC cows. During HGC, pancreatic insulin secretion was lower, but the glucose infusion rate was higher pp than ap in both groups. Plasma concentrations of nonesterified fatty acids decreased during HGC and EGHIC, but in both

  3. Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose.

    Science.gov (United States)

    Jalloh, Ibrahim; Carpenter, Keri L H; Grice, Peter; Howe, Duncan J; Mason, Andrew; Gallagher, Clare N; Helmy, Adel; Murphy, Michael P; Menon, David K; Carpenter, T Adrian; Pickard, John D; Hutchinson, Peter J

    2015-01-01

    Increased 'anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-(13)C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. (13)C enrichment for glycolytic 2,3-(13)C2 lactate was the median 5.4% (interquartile range (IQR) 4.6-7.5%) in TBI brain and 4.2% (2.4-4.4%) in 'normal' brain (P<0.01). The ratio of PPP-derived 3-(13)C lactate to glycolytic 2,3-(13)C2 lactate was median 4.9% (3.6-8.2%) in TBI brain and 6.7% (6.3-8.9%) in 'normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=-0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than 'normal' brain. Several TBI patients exhibited PPP-lactate elevation above the 'normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain.

  4. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Directory of Open Access Journals (Sweden)

    Vladimir O Murovets

    Full Text Available The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+ inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-. Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  5. Response of C2C12 Myoblasts to Hypoxia: The Relative Roles of Glucose and Oxygen in Adaptive Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wei Li

    2013-01-01

    Full Text Available Background. Oxygen and glucose are two important nutrients for mammalian cell function. In this study, the effect of glucose and oxygen concentrations on C2C12 cellular metabolism was characterized with an emphasis on detecting whether cells show oxygen conformance (OC in response to hypoxia. Methods. After C2C12 cells being cultured in the levels of glucose at 0.6 mM (LG, 5.6 mM (MG, or 23.3 mM(HG under normoxic or hypoxic (1% oxygen condition, cellular oxygen consumption, glucose consumption, lactate production, and metabolic status were determined. Short-term oxygen consumption was measured with a novel oxygen biosensor technique. Longer-term measurements were performed with standard glucose, lactate, and cell metabolism assays. Results. It was found that oxygen depletion in normoxia is dependent on the glucose concentration in the medium. Cellular glucose uptake and lactate production increased significantly in hypoxia than those in normoxia. In hypoxia the cellular response to the level of glucose was different to that in normoxia. The metabolic activities decreased while glucose concentration increased in normoxia, while in hypoxia, metabolic activity was reduced in LG and MG, but unchanged in HG condition. The OC phenomenon was not observed in the present study. Conclusions. Our findings suggested that a combination of low oxygen and low glucose damages the viability of C2C12 cells more seriously than low oxygen alone. In addition, when there is sufficient glucose, C2C12 cells will respond to hypoxia by upregulating anaerobic respiration, as shown by lactate production.

  6. Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Y.Y.; Seto, K.; Saito, H.; Kawakami, M.

    A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of /sup 14/C-1, 5-citric acid and /sup 14/C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment.

  7. Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

    Science.gov (United States)

    Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

    2016-06-01

    What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC

  8. Effects of Cooling and Supplemental Bovine Somatotropin on Milk Production relating to Body Glucose Metabolism and Utilization of Glucose by the Mammary Gland in Crossbred Holstein Cattle

    Directory of Open Access Journals (Sweden)

    Siravit Sitprija

    2010-01-01

    Full Text Available Problem statement: The low milk yield and shorter persistency of lactation of dairy cattle is the major problem for the dairy practices in the tropics. High environmental temperatures and rapid decline of plasma growth hormone level can influence milk production. Regulation of the milk yield of animals is mainly based on the mechanisms governing the quantity of glucose extracted by the mammary gland for lactose biosynthetic pathways. The mechanism(s underlying the effects of cooling and supplemental bovine somatotropin on milk production relating to body glucose metabolism and intracellular metabolism of glucose in the mammary gland of crossbred Holstein cattle in the tropics have not been investigated to date. Approach: Ten crossbred 87.5% Holstein cows were divided into two groups of five animals each. Animals were housed in Normal Shade barn (NS as non-cooled cows and cows in the second group were housed in barn which was equipped with a two Misty-Fan cooling system (MF as cooled cows. Supplementation of recombinant bovine Somatotropin (rbST (POSILAC, 500 mg per cow were performed in both groups to study body glucose metabolism and the utilization of glucose in the mammary gland using a continuous infusion of [3-3H] glucose and [U- 14C] glucose as markers in early, mid and late stages of lactation. Results: Milk yield significantly increased in both groups during supplemental rbST with a high level of mammary blood flow. Body glucose turnover rates were not significant different between cooled and non-cooled cows whether supplemental rbST or not. The glucose taken up by the mammary gland of both non-cooled and cooled cows increased flux through the lactose synthesis and the pentose cycle pathway with significant increases in NADPH formation for fatty acid synthesis during rbST supplementation. The utilization of glucose carbon incorporation into milk appeared to increase in milk lactose and milk triacylglycerol but not for

  9. Glutamate Acts as a Key Signal Linking Glucose Metabolism to Incretin/cAMP Action to Amplify Insulin Secretion

    OpenAIRE

    Ghupurjan Gheni; Masahito Ogura; Masahiro Iwasaki; Norihide Yokoi; Kohtaro Minami; Yasumune Nakayama; Kazuo Harada; Benoit Hastoy; Xichen Wu; Harumi Takahashi; Kazushi Kimura; Toshiya Matsubara; Ritsuko Hoshikawa; Naoya Hatano; Kenji Sugawara

    2014-01-01

    Summary Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shu...

  10. Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism.

    Science.gov (United States)

    Shinoda, Gen; Shyh-Chang, Ng; Soysa, T Yvanka de; Zhu, Hao; Seligson, Marc T; Shah, Samar P; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P; Gregory, Richard I; Asara, John M; Cantley, Lewis C; Moss, Eric G; Daley, George Q

    2013-08-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here, we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling.

  11. Effects of glucogenic and ketogenic feeding strategies on splanchnic glucose and amino acid metabolism in postpartum transition Holstein cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2012-01-01

    Nine periparturient Holstein cows catheterized in major splanchnic vessels were used in a complete randomized design with repeated measurements to investigate effects of glucogenic and ketogenic feeding strategies on splanchnic metabolism of glucose and amino acids. At parturition, cows were...... incremental increase in hepatic glucose release rather than hepatic catabolism of amino acids....

  12. Effect of Intermittent Hypoxia and Rimonabant on Glucose Metabolism in Rats: Involvement of Expression of GLUT4 in Skeletal Muscle

    OpenAIRE

    Wang, Xiaoya; Yu, Qin; Yue, Hongmei; Zeng, Shuang; Cui, Fenfen

    2015-01-01

    Background Obstructive sleep apnea (OSA) and its main feature, chronic intermittent hypoxia (IH) during sleep, is closely associated with insulin resistance (IR) and diabetes. Rimonabant can regulate glucose metabolism and improve IR. The present study aimed to assess the effect of IH and rimonabant on glucose metabolism and insulin sensitivity, and to explore the possible mechanisms. Material/Methods Thirty-two rats were randomly assigned into 4 groups: Control group, subjected to intermitte...

  13. Chronic fatigue syndrome in middle-aged women: the role of disorders of glucose metabolism

    Directory of Open Access Journals (Sweden)

    Anastasiya V Pleshcheva

    2014-12-01

    Full Text Available Objectives: To determine the prevalence of chronic fatigue syndrome (CFS among middle-aged women and to assess the role of glucose metabolism disturbances in the development of this pathology. Materials and Methods: The study included 231 women from 40 to 60 years old (mean age 52.3 ± 5 years, observed at urban polyclinic in Moscow, who was referred to or was observed by an endocrinologist (n = 142, group 1, therapist (n = 56, group 2 or had a prophylactic medical examinations (n = 33, group 3. We recorded demographic and anthropometric data, accessed levels of glucose, glycated hemoglobin, insulin and calculated BMI and HOMA indexes. Results: The prevalence of CFS in the whole group of patients studied was 27%. The highest frequency of CFS is registered in the group of patients observed by the endocrinologist – 35%, and at dispensary examination – 21%, which was significantly different from the prevalence of CFS in patients seeking an appointment with a therapist – 13% (p = 0.002 and p = 0.03 for Fisher's exact test, respectively. Higher BMI, blood glucose, glycosylated hemoglobin, and HOMA insulin resistance index as naturally expected were observed in group 1, but after further division for the presence or absence of CFS, significant differences for patients with CFS were only higher fasting glucose levels in group 2. Conclusions: We determined the prevalence of CFS in the examined groups of patients and showed only a weak correlation of CFS and disturbances of glucose metabolism.

  14. Cocoa and Whey Protein Differentially Affect Markers of Lipid and Glucose Metabolism and Satiety.

    Science.gov (United States)

    Campbell, Caroline L; Foegeding, E Allen; Harris, G Keith

    2016-03-01

    Food formulation with bioactive ingredients is a potential strategy to promote satiety and weight management. Whey proteins are high in leucine and are shown to decrease hunger ratings and increase satiety hormone levels; cocoa polyphenolics moderate glucose levels and slow digestion. This study examined the effects of cocoa and whey proteins on lipid and glucose metabolism and satiety in vitro and in a clinical trial. In vitro, 3T3-L1 preadipocytes were treated with 0.5-100 μg/mL cocoa polyphenolic extract (CPE) and/or 1-15 mM leucine (Leu) and assayed for lipid accumulation and leptin production. In vivo, a 6-week clinical trial consisted of nine panelists (age: 22.6 ± 1.7; BMI: 22.3 ± 2.1) consuming chocolate-protein beverages once per week, including placebo, whey protein isolate (WPI), low polyphenolic cocoa (LP), high polyphenolic cocoa (HP), LP-WPI, and HP-WPI. Measurements included blood glucose and adiponectin levels, and hunger ratings at baseline and 0.5-4.0 h following beverage consumption. At levels of 50 and 100 μg/mL, CPE significantly inhibited preadipocyte lipid accumulation by 35% and 50%, respectively, and by 22% and 36% when combined with 15 mM Leu. Leu treatment increased adipocyte leptin production by 26-37%. In the clinical trial, all beverages significantly moderated blood glucose levels 30 min postconsumption. WPI beverages elicited lowest peak glucose levels and HP levels were significantly lower than LP. The WPI and HP beverage treatments significantly increased adiponectin levels, but elicited no significant changes in hunger ratings. These trends suggest that combinations of WPI and cocoa polyphenols may improve markers of metabolic syndrome and satiety. PMID:26987021

  15. The influence of social status on hepatic glucose metabolism in rainbow trout Oncorhynchus mykiss.

    Science.gov (United States)

    Gilmour, Kathleen M; Kirkpatrick, Sheryn; Massarsky, Andrey; Pearce, Brenda; Saliba, Sarah; Stephany, Céleste-Élise; Moon, Thomas W

    2012-01-01

    The effects of chronic social stress on hepatic glycogen metabolism were examined in rainbow trout Oncorhynchus mykiss by comparing hepatocyte glucose production, liver glycogen phosphorylase (GP) activity, and liver β-adrenergic receptors in dominant, subordinate, control, fasted, and cortisol-treated fish. Hepatocyte glucose production in subordinate fish was approximately half that of dominant fish, reflecting hepatocyte glycogen stores in subordinate trout that were just 16% of those in dominant fish. Fasting and/or chronic elevation of cortisol likely contributed to these differences based on similarities among subordinate, fasted, and cortisol-treated fish. However, calculation of the "glycogen gap"--the difference between glycogen stores used and glucose produced--suggested an enhanced gluconeogenic potential in subordinate fish that was not present in fasted or cortisol-treated trout. Subordinate, fasted, and cortisol-treated trout also exhibited similar GP activities (both total activity and that of the active or a form), and these activities were in all cases significantly lower than those in control trout, perhaps reflecting an attempt to protect liver glycogen stores or a modified capacity to activate GP. Dominant trout exhibited the lowest GP activities (20%-24% of the values in control trout). Low GP activities, presumably in conjunction with incoming energy from feeding, allowed dominant fish to achieve the highest liver glycogen concentrations (double the value in control trout). Liver membrane β-adrenoceptor numbers (assessed as the number of (3)H-CGP binding sites) were significantly lower in subordinate than in dominant trout, although this difference did not translate into attenuated adrenergic responsiveness in hepatocyte glucose production in vitro. Transcriptional regulation, likely as a result of fasting, was indicated by significantly lower β(2)-adrenoceptor relative mRNA levels in subordinate and fasted trout. Collectively, the data

  16. Impaired glucose metabolism in HIV-infected pregnant women: a retrospective analysis.

    Science.gov (United States)

    Moore, Rebecca; Adler, Hugh; Jackson, Valerie; Lawless, Mairead; Byrne, Maria; Eogan, Maeve; Lambert, John S

    2016-06-01

    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. We conducted a retrospective review of all HIV-infected women attending a combined infectious disease and antenatal clinic between 2007 and 2013 who underwent a 100 g oral glucose tolerance test (OGTT) at 24-28 weeks. We grouped the patients based on whether their OGTT result was normal or abnormal, and compared the groups using standard parametric tests (t-test and Fisher's exact test). Of 263 women with HIV who attended the clinic, 142 (53.9%) attended for OGTT and were eligible for inclusion. The mean age was 31 years (SD 5.37), all women were of European or African origin and 33.7% had a body mass index ≥30 kg/m(2) About 93.7% were on PI-based regimens. At delivery, the mean CD4 count was 526 cells/µL, and 13% of patients had a detectable viraemia. The prevalence of IGT was 2.8%, while the prevalence of GDM was 2.1%. Also, 71.4% (n = 5) of women with abnormal glucose metabolism were taking PIs versus 94.8% (n = 128) of normoglycaemic women (p = 0.06). We did not confirm an increased rate of GDM in HIV-infected women in our patient population and found no association between PI use and GDM. PMID:25999164

  17. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction.

    Science.gov (United States)

    Barry, James S; Rozance, Paul J; Brown, Laura D; Anthony, Russell V; Thornburg, Kent L; Hay, William W

    2016-04-01

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128-132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r(2 )= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic-euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply in the IUGR condition via increased glucose uptake and

  18. Impact of switching from lopinavir/ritonavir to boosted and un-boosted atazanavir on glucose metabolism: the ATAzanavir & GLUcose metabolism (ATAGLU) study.

    Science.gov (United States)

    d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Zaccarelli, Mauro; Ascoli-Bartoli, Tommaso; Bianchi, Luigi; Bellelli, Valeria; De Girolamo, Gabriella; Serafino, Sara; Giustini, Noemi; Mastroianni, Claudio M; Vullo, Vincenzo

    2016-07-01

    Previous studies have reported that protease inhibitors (PIs) can contribute to glycaemic alterations. However, there are few trials examining the direct effect of a single PI. The objective of the study was to evaluate the modifications of glucose and lipid profiles after a switch from lopinavir/ritonavir (LPV/r) to atazanavir, used as ritonavir-boosted (ATV/r) or un-boosted. We conducted a retrospective observational cohort study on the effect of ATV/(r) on glycaemic metabolism (ATAGLU) in patients with undetectable levels of HIV-RNA who switched from LPV/r. In total, 235 patients treated for 48 weeks with LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) and with undetectable HIV-RNA were included: 134 continued LPV/r after the initial 48 weeks and 101 switched to ATV(/r) (18.3% to ATV; 24.7% to ATV/r). A significant decrease in mean glucose level and insulin resistance was observed in patients who switched to ATV(/r). The mean cholesterol triglyceride levels increased in the LPV/r group and decreased among the patients who switched. A significant increase of CD4 T cells with undetectable levels of HIV-RNA was observed in all groups. The long-term results obtained in this real-life study suggest that patients who have achieved initial suppression on a regimen including LPV/r + two NRTIs can switch to ATV/(r) + two NRTIs with an improvement in lipid and glycaemic metabolism.

  19. Protective properties of radio-chemoresistant glioblastoma stem cell clones are associated with metabolic adaptation to reduced glucose dependence.

    Directory of Open Access Journals (Sweden)

    Fei Ye

    Full Text Available Glioblastoma stem cells (GSC are a significant cell model for explaining brain tumor recurrence. However, mechanisms underlying their radiochemoresistance remain obscure. Here we show that most clonogenic cells in GSC cultures are sensitive to radiation treatment (RT with or without temozolomide (TMZ. Only a few single cells survive treatment and regain their self-repopulating capacity. Cells re-populated from treatment-resistant GSC clones contain more clonogenic cells compared to those grown from treatment-sensitive GSC clones, and repeated treatment cycles rapidly enriched clonogenic survival. When compared to sensitive clones, resistant clones exhibited slower tumor development in animals. Upregulated genes identified in resistant clones via comparative expression microarray analysis characterized cells under metabolic stress, including blocked glucose uptake, impaired insulin/Akt signaling, enhanced lipid catabolism and oxidative stress, and suppressed growth and inflammation. Moreover, many upregulated genes highlighted maintenance and repair activities, including detoxifying lipid peroxidation products, activating lysosomal autophagy/ubiquitin-proteasome pathways, and enhancing telomere maintenance and DNA repair, closely resembling the anti-aging effects of caloric/glucose restriction (CR/GR, a nutritional intervention that is known to increase lifespan and stress resistance in model organisms. Although treatment-introduced genetic mutations were detected in resistant clones, all resistant and sensitive clones were subclassified to either proneural (PN or mesenchymal (MES glioblastoma subtype based on their expression profiles. Functional assays demonstrated the association of treatment resistance with energy stress, including reduced glucose uptake, fatty acid oxidation (FAO-dependent ATP maintenance, elevated reactive oxygen species (ROS production and autophagic activity, and increased AMPK activity and NAD(+ levels accompanied by

  20. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study.

    Directory of Open Access Journals (Sweden)

    Maria Lankinen

    Full Text Available BACKGROUND: Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1 whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group, (2 Whole grain enriched diet (WGED group, which includes principally the same grain products as group (1, but with no change in fish or berry consumption, and (3 refined wheat breads (Control. Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3 long-chain PUFAs increased (False Discovery Rate p-values <0.05. Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3 PUFA. CONCLUSIONS/SIGNIFICANCE: The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a

  1. Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer

    Science.gov (United States)

    Wang, Jihong; Weygand, Joseph; Hwang, Ken-Pin; Mohamed, Abdallah S. R.; Ding, Yao; Fuller, Clifton D.; Lai, Stephen Y.; Frank, Steven J.; Zhou, Jinyuan

    2016-01-01

    Imaging metabolic dysfunction, a hallmark of solid tumors, usually requires radioactive tracers. Chemical exchange saturation transfer (CEST) imaging can potentially detect and visualize glucose uptake and metabolism, without the need for radioisotopes. Here, we tested the feasibility of using glucose CEST (glucoCEST) to image unlabeled glucose uptake in head and neck cancer by using a clinical 3T magnetic resonance imaging (MRI) scanner. The average CEST contrast between tumors and normal tissue in 17 patients was 7.58% (P = 0.006) in the 3–4 ppm offset frequency range and 5.06% (P = 0.02) in 1–5 ppm range. In a subgroup of eight patients, glucoCEST signal enhancement was higher in tumors than in normal muscle (4.98% vs. 1.28%, P < 0.021). We conclude that glucoCEST images of head and neck cancer can be obtained with a clinical 3T MRI scanner. PMID:27461165

  2. Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion.

    Science.gov (United States)

    Patterson, Jessica N; Cousteils, Katelyn; Lou, Jennifer W; Manning Fox, Jocelyn E; MacDonald, Patrick E; Joseph, Jamie W

    2014-05-01

    It is well known that mitochondrial metabolism of pyruvate is critical for insulin secretion; however, we know little about how pyruvate is transported into mitochondria in β-cells. Part of the reason for this lack of knowledge is that the carrier gene was only discovered in 2012. In the current study, we assess the role of the recently identified carrier in the regulation of insulin secretion. Our studies show that β-cells express both mitochondrial pyruvate carriers (Mpc1 and Mpc2). Using both pharmacological inhibitors and siRNA-mediated knockdown of the MPCs we show that this carrier plays a key role in regulating insulin secretion in clonal 832/13 β-cells as well as rat and human islets. We also show that the MPC is an essential regulator of both the ATP-regulated potassium (KATP) channel-dependent and -independent pathways of insulin secretion. Inhibition of the MPC blocks the glucose-stimulated increase in two key signaling molecules involved in regulating insulin secretion, the ATP/ADP ratio and NADPH/NADP(+) ratio. The MPC also plays a role in in vivo glucose homeostasis as inhibition of MPC by the pharmacological inhibitor α-cyano-β-(1-phenylindol-3-yl)-acrylate (UK5099) resulted in impaired glucose tolerance. These studies clearly show that the newly identified mitochondrial pyruvate carrier sits at an important branching point in nutrient metabolism and that it is an essential regulator of insulin secretion. PMID:24675076

  3. Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer.

    Science.gov (United States)

    Wang, Jihong; Weygand, Joseph; Hwang, Ken-Pin; Mohamed, Abdallah S R; Ding, Yao; Fuller, Clifton D; Lai, Stephen Y; Frank, Steven J; Zhou, Jinyuan

    2016-01-01

    Imaging metabolic dysfunction, a hallmark of solid tumors, usually requires radioactive tracers. Chemical exchange saturation transfer (CEST) imaging can potentially detect and visualize glucose uptake and metabolism, without the need for radioisotopes. Here, we tested the feasibility of using glucose CEST (glucoCEST) to image unlabeled glucose uptake in head and neck cancer by using a clinical 3T magnetic resonance imaging (MRI) scanner. The average CEST contrast between tumors and normal tissue in 17 patients was 7.58% (P = 0.006) in the 3-4 ppm offset frequency range and 5.06% (P = 0.02) in 1-5 ppm range. In a subgroup of eight patients, glucoCEST signal enhancement was higher in tumors than in normal muscle (4.98% vs. 1.28%, P < 0.021). We conclude that glucoCEST images of head and neck cancer can be obtained with a clinical 3T MRI scanner. PMID:27461165

  4. The Effect of Exercise on Glucose Metabolism in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Tuba Tulay Koca

    2015-09-01

    Full Text Available Diabetes mellitus is one of the major causes of disability and death due to the complications accompanying this disease. The incidence of type 2 diabetes mellitus and insulin resistance has increased worldwide during the last decades, despite the development of effective drug therapy and improved clinical diagnoses. Recent epidemiological studies indicate that individuals who maintain a physically active lifestyle are much less likely to develop impaired glucose tolerance and diabetes mellitus. Additional to protective effect of physical activity for individuals at highest risk of developing diabetes mellitus, physical activity has positive impacts on fasting glucose, insulin sensitivity and blood glucose level for patients with overt diabetes. The essential mechanism of exercises is enhancing sensitivity of insulin on pheripheral tissues (especially skeletal muscle. With exercise training significant improvements in glucose metabolism is observed in many of these studies. Especially, the improvements in insulin sensitivity with exercise training observed better in high magnitude of aerobic exercises. Also adaptation of patients is very high to combined type exercises. However worldwide standardization of these training programmes in many of the studies is lacking and current practice in daily life is unsatisfactory. [Archives Medical Review Journal 2015; 24(3.000: 306-316

  5. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  6. Effect of dietary protein on lipid and glucose metabolism: implications for metabolic health

    NARCIS (Netherlands)

    Rietman, A.

    2015-01-01

    Abstract Background: Diet is an important factor in the development of the Metabolic Syndrome (Mets) and type 2 Diabetes Mellitus. Accumulation of intra hepatic lipid (IHL) can result in non-alcoholic fatty liver disease (NAFLD), which is sometimes considered the he

  7. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Directory of Open Access Journals (Sweden)

    Darren J Creek

    2015-03-01

    Full Text Available Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

  8. Study of regional cerebral metabolic rate of glucose with positron emission computed tomography in Alzheimer's disease

    International Nuclear Information System (INIS)

    Using positron emission computed tomography with F-18 fluoro-D-deoxyglucose, regional cerebral metabolic rate of glucose (rCMRglc) was measured in 8 patients with Alzheimer's disease and 3 healthy volunteers. A decreased rCMRglc was observed in the widespread cortex and basal ganglia of the cerebrum, but not observed in white matter, thalamus, and cerebellum. There was no bilateral difference. rCMRglc was the lowest in the parietal lobe, followed by the temporal lobe and the curvature of the frontal lobe. A decrease in rCMRglu was relatively mild in the inner part of the frontal lobe, primary sensory and motor area of the cerebral cortex, and cerebral basilar ganglia. Alzheimer's disease proved to be characterized by severe glucose metabolic disorder in the association area of the bilateral cerebral cortices. The degree of metabolic disorder was correlated with the degree of dementia in the outer part of the left frontal lobe and the curvature of the cerebral cortex. (Namekawa, K.)

  9. Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

    Science.gov (United States)

    Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

    2012-09-01

    The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

  10. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    Science.gov (United States)

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26683700

  11. Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain

    DEFF Research Database (Denmark)

    Zhang, Yiming; Liu, Guodong; Engqvist, Martin K. M.;

    2015-01-01

    Background: A Saccharomyces cerevisiae strain carrying deletions in all three pyruvate decarboxylase (PDC) genes (also called Pdc negative yeast) represents a non-ethanol producing platform strain for the production of pyruvate derived biochemicals. However, it cannot grow on glucose as the sole...... carbon source, and requires supplementation of C2 compounds to the medium in order to meet the requirement for cytosolic acetyl-CoA for biosynthesis of fatty acids and ergosterol. Results: In this study, a Pdc negative strain was adaptively evolved for improved growth in glucose medium via serial...... expression of several hexose transporter genes. The non-synonymous mutations in HXT2 and CIT1 may function in the presence of mutated MTH1 alleles and could be related to an altered central carbon metabolism in order to ensure production of cytosolic acetyl-CoA in the Pdc negative strain....

  12. Study on the effect of valproate (VPA) on glucose metabolism in pediatric patients with epilepsy

    International Nuclear Information System (INIS)

    Objective: To study the effect on glucose metabolism in pediatric patients with epilepsy under valproate treatment. Methods: Fasting serum glucose (with oxidase method) and insulin (with RIA) levels, insulin resistance index, body weight, BMI were examined in (1) 65 pediatric patients with epilepsy before valproate treatment (2) 65 patients after 3 months' valproate treatment (3) 65 patients after 6 months' treatment and (4) 65 controls. Results: In the patients after 3 months' treatment, the body weight, BMI, fasting insulin levels were significantly higher than those in patients before treatment (P 0.05). The calculated HOMA did not change much throughout the whole study. The proportion of patients with increased appetite after 6 months' treatment was 47 /65 (vs 20 /65 before treatment, P < 0.05). Conclusion: The increase of body weight and BMI asually observed during valproate treatment is mainly due to increased appetite with limited increase of fasting insulin level. Insulin resistance was not found in present study. (authors)

  13. The effect of microbial glucose metabolism on bytownite feldspar dissolution rates between 5 and 35 C

    Energy Technology Data Exchange (ETDEWEB)

    Welch, S.A.; Ullman, W.J.

    1999-10-01

    The rate of Si release from dissolving bytownite feldspar in abiotic batch reactors increased as temperatures increased from 5 to 35 C. Metabolically inert subsurface bacteria (bacteria in solution with no organic substrate) had no apparent effect on dissolution rates over this temperature range. When glucose was added to the microbial cultures, the bacteria responded by producing gluconic acid, which catalyzed the dissolution reaction by both proton- and ligand-promoted mechanisms. The metabolic production, excretion, and consumption of gluconic acid in the course of glucose oxidation, and therefore, the degree of microbial enhancement of mineral dissolution, depend on temperature. There was little accumulation of gluconic acid and therefore, no significant enhancement of mineral dissolution rates at 35 C compared to the abiotic controls. At 20 C, gluconate accumulated in the experimental solutions only at the beginning of the experiment and led to a twofold increase in dissolved Si release compared to the controls, primarily by the ligand-promoted dissolution mechanism. There was significant accumulation of gluconic acid in the 5 C experiment, which is reflected in a significant reduction in pH, leading to 20-fold increase in Si release, primarily attributable to the proton-promoted dissolution mechanism. These results indicate that bacteria and microbial metabolism can affect mineral dissolution rates in organic-rich, nutrient-poor environments; the impact of microbial metabolism on aluminum silicate dissolution rates may be greater at lower rather than at higher temperatures due to the metabolic accumulation of dissolution-enhancing protons and ligands in solution.

  14. Effect of triiodothyronine and insulin on glucose metabolism in tissue explants and isolated adipocytes from lean and obese Zucker rats

    International Nuclear Information System (INIS)

    Glucose metabolism in adipocytes from 6 week old lean and obese Zucker rats were sensitive to direct and chronic treatment with insulin and triidothyronine (T3). Insulin had a large stimulatory effect on glucose metabolism in acutely isolated adipocytes. This effect was greater in the lean than in the obese. Fatty acid, CO2, and glycerol-glyceride formation from radiolabeled glucose was elevated in the obese over the leans. Pretreatment of isolated adipocytes with pharmacological concentrations of T3 for 30 minutes prior to the measurement of glucose metabolism had a greater effect on lean than obese adipocytes. The presence of insulin was required to observe the acute effects of T3. A 2-hour exposure to physiological levels of T3 in the presence of insulin in both lean and obese adipocytes decreased lipogenesis. In the absence of insulin, a 2 hour pretreatment with physiological levels of T3 in tissue from a euthyroid animal produced increased lipogenesis

  15. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng

    2016-05-01

    Full Text Available Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient–host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control and hippocampus (cognitive processing from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

  16. Effect of systemically increasing human full-length Klotho on glucose metabolism in db/db mice.

    Science.gov (United States)

    Forsberg, E A; Olauson, H; Larsson, T; Catrina, S B

    2016-03-01

    The metabolic effects of antiaging Klotho were previously investigated in vivo by genetic manipulation. We have here studied the metabolic effect of physiologic levels of circulating full length Klotho in db/db mice. Increasing the full-length human Klotho levels has a positive effect on blood glucose through increasing insulin secretion. PMID:26806457

  17. Quantitative on-line monitoring of hippocampus glucose and lactate metabolism in organotypic cultures using biosensor technology

    NARCIS (Netherlands)

    Gramsbergen, JB; Leegsma-Vogt, G; Venema, K; Noraberg, J; Korf, J

    2003-01-01

    Quantitative glucose and lactate metabolism was assessed in continuously perfused organotypic hippocampal slices under control conditions and during exposure to glutamate and drugs that interfere with aerobic and anaerobic metabolism. On-line detection was possible with a system based on slow perfus

  18. Thermodynamics of Microbial Growth Coupled to Metabolism of Glucose, Ethanol, Short-Chain Organic Acids, and Hydrogen ▿ †

    Science.gov (United States)

    Roden, Eric E.; Jin, Qusheng

    2011-01-01

    A literature compilation demonstrated a linear relationship between microbial growth yield and the free energy of aerobic and anaerobic (respiratory and/or fermentative) metabolism of glucose, ethanol, formate, acetate, lactate, propionate, butyrate, and H2. This relationship provides a means to estimate growth yields for modeling microbial redox metabolism in soil and sedimentary environments. PMID:21216913

  19. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar;

    2012-01-01

    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors...... years. The magnitudes of CMRO(2) and CBF declined in large parts of the cerebral cortex, including association areas, but the primary motor and sensory areas were relatively spared. We found significant increases of OEF in frontal and parietal cortices, excluding primary motor and somatosensory regions......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

  20. Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia

    DEFF Research Database (Denmark)

    Gejl, Michael; Egefjord, Lærke; Lerche, Susanne;

    2012-01-01

    Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD...... in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia....

  1. Glucose Metabolism in T Cells and Monocytes: New Perspectives in HIV Pathogenesis

    Science.gov (United States)

    Palmer, Clovis S.; Cherry, Catherine L.; Sada-Ovalle, Isabel; Singh, Amit; Crowe, Suzanne M.

    2016-01-01

    Activation of the immune system occurs in response to the recognition of foreign antigens and receipt of optimal stimulatory signals by immune cells, a process that requires energy. Energy is also needed to support cellular growth, differentiation, proliferation, and effector functions of immune cells. In HIV-infected individuals, persistent viral replication, together with inflammatory stimuli contributes to chronic immune activation and oxidative stress. These conditions remain even in subjects with sustained virologic suppression on antiretroviral therapy. Here we highlight recent studies demonstrating the importance of metabolic pathways, particularly those involving glucose metabolism, in differentiation and maintenance of the activation states of T cells and monocytes. We also discuss how changes in the metabolic status of these cells may contribute to ongoing immune activation and inflammation in HIV- infected persons and how this may contribute to disease progression, establishment and persistence of the HIV reservoir, and the development of co-morbidities. We provide evidence that other viruses such as Epstein–Barr and Flu virus also disrupt the metabolic machinery of their host cells. Finally, we discuss how redox signaling mediated by oxidative stress may regulate metabolic responses in T cells and monocytes during HIV infection. PMID:27211546

  2. Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Bolado-Carrancio, A. [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain); Riancho, J.A. [Department of Internal Medicine, Hospital U.M. Valdecilla-IDIVAL, University of Cantabria, RETICEF, Santander (Spain); Sainz, J. [Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, Santander (Spain); Rodríguez-Rey, J.C., E-mail: rodriguj@unican.es [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain)

    2014-04-04

    Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.

  3. Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

    International Nuclear Information System (INIS)

    Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose leve