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Sample records for cerebral glucose metabolic

  1. Cerebral glucose metabolism in patients with spasmodic torticollis

    NARCIS (Netherlands)

    MagyarLehmann, S; Antonini, A; Roelcke, U; Maguire, RP; Missimer, J; Leenders, KL

    1997-01-01

    The pathophysiology of spasmodic torticollis is not clear. Basal ganglia dysfunction has been suggested to underlie this clinical syndrome. We studied resting cerebral glucose metabolism in 10 spasmodic torticollis patients and 10 healthy controls by using positron-emission tomography and [F-18]2-fl

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

    DEFF Research Database (Denmark)

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    2012-01-01

    The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow...... not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation...

  3. 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.

  4. 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.).

  5. Local cerebral glucose metabolism during controlled hypoxemia in rats.

    Science.gov (United States)

    Pulsinelli, W A; Duffy, T E

    1979-05-11

    2-Deoxy-[14C]glucose metabolism was examined in brains of hypoxic, normotensive rats by autoradiography, which revealed alternating cortical columns of high and low metabolism. Activity in white matter was increased severalfold over that in adjacent gray matter. The columns were anatomically related to penetrating cortical arteries with areas between arteries demonstrating higher rates of metabolism. The results suggest the presence of interarterial tissue oxygen gradients that influence regional glucose metabolism. The relatively greater sensitivity of white matter metabolism to hypoxia may lead to an understanding of white matter damage in postanoxic leukoencephalopathy.

  6. Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.

    OpenAIRE

    Balestri, P; Lucignani, G; Fois, A.; Magliani, L; Calistri, L; Grana, C.; Di Bartolo, R M; Perani, D; Fazio, F.

    1994-01-01

    Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This fi...

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

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, R.L.; London, E.D.; Links, J.M.; Cascella, N.G. (NIDA Addiction Research Center, Baltimore, MD (USA))

    1990-12-01

    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.

  8. 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).

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

    Science.gov (United States)

    Haier, Richard J.; And Others

    1995-01-01

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

  10. [Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography].

    Science.gov (United States)

    Franck, G; Salmon, E; Poirrier, R; Sadzot, B; Franco, G

    1987-03-01

    Measurements of regional cerebral glucose uptake by the 18F-fluorodeoxyglucose technique (18FDG) and positron emission tomography (PET) along with polygraph recordings were made serially during relaxed wakefulness and different stages of nocturnal sleep in two right-handed normal volunteers. During stage III-IV sleep, values declined diffusely in both hemispheric regions (-31%), thalamus (-33%), cerebellum (-33%) and brain stem (-25%). During paradoxical sleep regional values increased diffusely compared with slow wave sleep. Compared to wakefulness, regional metabolic values seemed to increase but the results were more variable from one volunteer to the other. These preliminary data indicate important regional alterations in cerebral metabolism between sleep states.

  11. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    Science.gov (United States)

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD.

  12. 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.

  13. 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

  14. Determination of patterns of regional cerebral glucose metabolism in normal aging and dementia

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    Alavi, A.; Chawluk, J.; Hurtig, H.; Dann, R.; Rosen, M.; Kushner, M.; Silver, F.; Reivich, M.

    1985-05-01

    Regional cerebral metabolic rates for glucose (rCMRGlc) were measured using 18F-FDG and positron emission tomography (PET) in 14 patients with probable Alzheimer's disease (AD) (age=64), 9 elderly controls (age=61), and 9 young controls (age=28). PET studies were performed without sensory stimulation or deprivation. Metabolic rates in individual brain regions were determined using an atlas overlay. Relative metabolic rates (rCMRGl c/global CMRGlc) were determined for all subjects. Comparison of young and elderly controls demonstrated significant decreases in frontal metabolism (rho<0.005) and right inferior parietal (IP) metabolism (rho<0.02) with normal aging. Patients with mild-moderate AD (NMAD) (n=8) when compared to age-matched controls, showed further reduction in right IP metabolism (rho<0.02). SAD patients also demonstrated metabolic decrements in left hemisphere language areas (rho<0.01). This latter finding is consistent with language disturbance observed late in the course of the disease. Out data reveal progressive changes in patterns of cerebral glucose utilization with aging and demential with reflect salient clinical features of these processes.

  15. Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Levy, D E; Duffy, T E

    1982-05-01

    Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and metabolism. Regional cerebral blood flow (rCBF) and cerebral glucose utilization (rCGU) were measured in adult rats prior to, during (only rCBF), and serially after transient forebrain ischemia. Animals were subjected to 30 minutes of forebrain ischemia by occluding both common carotid arteries 24 hours after cauterizing the vertebral arteries. Regional CBF was measured by the indicator-fractionation technique using 4-iodo-[14C]-antipyrine. Regional CGU was measured by the 2-[14C]deoxyglucose method. The results were correlated with the distribution and progression of ischemic neuronal damage in animals subjected to an identical ischemic insult. Cerebral blood flow to forebrain after 30 minutes of moderate to severe ischemia (less than 10% control CBF) was characterized by 5 to 15 minutes of hyperemia; rCBF then fell below normal and remained low for as long as 24 hours. Post-ischemic glucose utilization in the forebrain, except in the hippocampus, was depressed below control values at 1 hour and either remained low (neocortex, striatum) or gradually rose to normal (white matter) by 48 hours. In the hippocampus, glucose utilization equaled the control value at 1 hour and fell below control between 24 and 48 hours. The appearance of moderate to severe morphological damage in striatum and hippocampus coincided with a late rise of rCBF above normal and with a fall of rCGU; the late depression of rCGU was usually preceded by a period during which metabolism was increased relative to adjacent tissue. Further refinement of these studies may help identify salvageable brain after ischemia and define ways to manipulate CBF and metabolism in the treatment of stroke.

  16. Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.

    Science.gov (United States)

    Balestri, P; Lucignani, G; Fois, A; Magliani, L; Calistri, L; Grana, C; Di Bartolo, R M; Perani, D; Fazio, F

    1994-01-01

    Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This finding suggests that the abnormalities seen on MRI are not due to defective blood supply, localised oedema, or grey matter heterotopic foci as previously hypothesised. The presence of the hypometabolic areas seems to be inconsistently related to the occurrence of seizures and is not proportional to the degree of mental impairment. This study provides evidence of a widespread cerebral hypometabolism that is not related to the presence of MRI abnormalities; conversely normal metabolism was present in the areas with an abnormal MRI signal. Images PMID:7798976

  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. A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS

    DEFF Research Database (Denmark)

    Blinkenberg, M; Jensen, C.V.; Holm, S;

    1999-01-01

    in longitudinal studies of MS patients, but little is known about the associated changes in cerebral neural function. METHODS: The authors studied 10 patients with clinically definite MS who underwent serial measurements of CMRglc, MRI T2-weighted total lesion area (TLA), and clinical evaluation of disability...... (Expanded Disability Status Scale [EDSS]) over a period of approximately 2 years (three examinations). CMRglc was calculated using PET and 18-fluorodeoxyglucose (FDG). RESULTS: The global cortical CMRglc decreased with time (p...OBJECTIVE: To study the time-related changes in cerebral metabolic rate of glucose (CMRglc) in MS patients and to correlate these with changes in MRI lesion load and disability. BACKGROUND: Measurements of MRI lesion load and neurologic disability are used widely to monitor disease progression...

  19. EFFECT OF ELECTRO0-SCALP ACUPUNCTURE ON GLUCOSE METABOLISM OF THE CEREBRAL REGIONS INVOLVING MENTAL ACTIVITY IN HEAL THY PEOPLE

    Institute of Scientific and Technical Information of China (English)

    HUANG Yong(黄泳); Win Moe Htut; LI Dong-jiang(李东江); TANG An-wu(唐安戊); LI Qiu-shi(李求实)

    2004-01-01

    Objective: To observe the effect of electro-scalp acupuncture on glucose metabolism of cerebral regions involving mental activity in healthy people. Methods: A total of 6 cases of volunteer healthy subjects (3 males and 3 females) ranging in age from 22 to 36 years were subjected to this study. Changes of cerebral glucose metabolism before and after electro-scalp acupuncture were observed by using positron emission tomography (PET) and semi-quantifying analysis method. Electro-scalp acupuncture stimulation (50 Hz, 2 mA) of Middle Line of Vertex (Dingzhongxian,顶中线,MS5), Middle Line of Forehead (Ezhongxian, 额中线,MS1) and bilateral Lateral Line 1 of Forehead (Epangyixian,额旁一线,MS2) was administered for 30 minutes. Then cerebral regions of interest (ROIs) were chosen and their average glucose metabolism levels (radioactivity of 18 fluorine deoxyglucose ) were analyzed. Results:After administration of electro-scalp acupuncture, the glucose metabolism levels in bilateral frontal lobes and bilateral caudate nuclei, left cingulate gyrus and right cerebellum increased significantly in comparison with those of pre-stimulation (P<0.05). Conclusion:Electro-scalp acupuncture of MS1, MS2 and MS5 can increase the glucose metabolism of certain cerebral regions involving in mental activity in healthy subjects.

  20. 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.

  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. Gender differences in age-related decline in regional cerebral glucose metabolism

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

    2007-07-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause.

  3. 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.

  4. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

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    Kwak, Young Bin; Cho, Sang Soo; Lee, Sung Ha; Chey, Jean Yung; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2004-07-01

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.1{+-}4.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.69{+-}0.09 {mu} g/dL), while 14 (mean age, 67.2{+-}4.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.27{+-}0.03 {mu} g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted.

  5. Positron computed tomography studies of cerebral glucose metabolism in man: theory and application in nuclear medicine.

    Science.gov (United States)

    Phelps, M E

    1981-01-01

    The capability of positron computed tomography (PCT) to delineate the substructures of the brain and its facility for accurately measuring the local tissue radioactivity concentration allow the application of tracer kinetic models for the study of local cerebral function in man. This principle and an adaptation of the 14C-deoxyglucose (DG) model of Sokoloff et al. with 18F-2-fluoro-deoxy-D-glucose (FDG) is being used at UCLA. Brookhaven National Laboratory, University of Pennsylvania, NIH, and the Massachusetts General Hospital to determine the local cerebral glucose metabolic rate (LCMRGIc) in normal man at rest and during sensory activation and the changes that occur in patients with a variety of cerebral disorders. Kinetic studies with PCT have been employed to measure the rate constants of the model in different gray and white matter structures of the brain in both normal and ischemic states. The precision of the method in normals has been shown to be about +/- 5% for 1.5-2.0 sq cm regions of the brain. Studies in normals have yielded values for hemispheric CMRGIc that are in agreement with measurement using the Kety-Schmidt technique and LCMRGIc values in agreement with values in monkeys using DG autoradiography. Studies in volunteers subjected to visual and auditory stimulation are demonstrating the potential of this technique for investigating the human brain's response to different stimuli. STudies in patients with stroke show excellent correlation between the degree, extent, and particular structures involved and the clinical symptoms. The method consistently detected hypometabolism in cortical, thalamic, and striatal tissues that were dysfunctional due to deactivation or damage but which appeared normal on x-ray CT. Studies in patients with partial epilepsy have shown hypometabolic zones that highly correlated anatomically with interictal EEG spike foci and were associated with normal x-ray CT studies in 77% of the patients studied. The studies on

  6. 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.

  7. 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...

  8. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.

    Science.gov (United States)

    Nofzinger, Eric A; Buysse, Daniel J; Miewald, Jean M; Meltzer, Carolyn C; Price, Julie C; Sembrat, Robert C; Ombao, Hernando; Reynolds, Charles F; Monk, Timothy H; Hall, Martica; Kupfer, David J; Moore, Robert Y

    2002-05-01

    Sleep is an essential human function. Although the function of sleep has generally been regarded to be restorative, recent data indicate that it also plays an important role in cognition. The neurobiology of human sleep is most effectively analysed with functional imaging, and PET studies have contributed substantially to our understanding of both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. In this study, PET was used to determine patterns of regional glucose metabolism in NREM sleep compared with waking. We hypothesized that brain structures related to waking cognitive function would show a persistence of function into the NREM sleep state. Fourteen healthy subjects (age range 21-49 years; 10 women, 4 men) underwent concurrent EEG sleep studies and [(18)F]fluoro-2-deoxy-D-glucose PET scans during waking and NREM sleep. Whole-brain glucose metabolism declined significantly from waking to NREM sleep. Relative decreases in regional metabolism from waking to NREM sleep occurred in wide areas of frontal, parietal, temporal and occipital association cortex, primary visual cortex, and in anterior/dorsomedial thalamus. After controlling for the whole-brain declines in absolute metabolism, relative increases in regional metabolism from waking to NREM were found bilaterally in the dorsal pontine tegmentum, hypothalamus, basal forebrain, ventral striatum, anterior cingulate cortex and extensive regions of the mesial temporal lobe, including the amygdala and hippocampus, and in the right dorsal parietal association cortex and primary somatosensory and motor cortices. The reductions in relative metabolism in NREM sleep compared with waking are consistent with prior findings from blood flow studies. The relative increases in glucose utilization in the basal forebrain, hypothalamus, ventral striatum, amygdala, hippocampus and pontine reticular formation are new observations that are in accordance with the view that NREM sleep is important to brain

  9. Increased interictal cerebral glucose metabolism in a cortical-subcortical network in drug naive patients with cryptogenic temporal lobe epilepsy.

    Science.gov (United States)

    Franceschi, M; Lucignani, G; Del Sole, A; Grana, C; Bressi, S; Minicucci, F; Messa, C; Canevini, M P; Fazio, F

    1995-01-01

    Positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) has been used to assess the pattern of cerebral metabolism in different types of epilepsies. However, PET with [18F]FDG has never been used to evaluate drug naive patients with cryptogenic temporal lobe epilepsy, in whom the mechanism of origin and diffusion of the epileptic discharge may differ from that underlying other epilepsies. In a group of patients with cryptogenic temporal lobe epilepsy, never treated with antiepileptic drugs, evidence has been found of significant interictal glucose hypermetabolism in a bilateral neural network including the temporal lobes, thalami, basal ganglia, and cingular cortices. The metabolism in these areas and frontal lateral cortex enables the correct classification of all patients with temporal lobe epilepsy and controls by discriminant function analysis. Other cortical areas--namely, frontal basal and lateral, temporal mesial, and cerebellar cortices--had bilateral increases of glucose metabolism ranging from 10 to 15% of normal controls, although lacking stringent statistical significance. This metabolic pattern could represent a pathophysiological state of hyperactivity predisposing to epileptic discharge generation or diffusion, or else a network of inhibitory circuits activated to prevent the diffusion of the epileptic discharge. PMID:7561924

  10. 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

  11. 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.

  12. The effect of diazepam sedation on cerebral glucose metabolism in Alzheimer's disease as measured using positron emission tomography.

    Science.gov (United States)

    Foster, N L; VanDerSpek, A F; Aldrich, M S; Berent, S; Hichwa, R H; Sackellares, J C; Gilman, S; Agranoff, B W

    1987-08-01

    The effect of sedation induced by intravenous diazepam on cerebral glucose metabolic activity was examined with [18F]2-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in five patients with probable Alzheimer's disease. Each subject was studied on 2 separate days: on one occasion at rest with eyes patched and ears open, and on the second when sedated with intravenous diazepam titrated to maintain stage II sleep by clinical and EEG criteria. Similar patterns of glucose uptake were observed in both the presence and the absence of sedation, but overall glucose utilization was depressed an average of 20% and was closely correlated with the amount of diazepam administered prior to the injection of FDG. The predominant temporoparietal hypometabolism and relative sparing of frontal metabolism observed in this disease are therefore not explained by differences in anxiety or activity level in this patient group. Utilization of diazepam sedation for PET study appears to be safe and may permit the study of patients otherwise unable to cooperate with FDG-PET procedures.

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

    Science.gov (United States)

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

    2014-01-01

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60–85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [18F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults. PMID:25463973

  14. 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.

  15. 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.

  16. 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...

  17. Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

    Energy Technology Data Exchange (ETDEWEB)

    Verfaillie, Sander C.J.; Adriaanse, Sofie M.; Binnewijzend, Maja A.A.; Benedictus, Marije R.; Ossenkoppele, Rik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Wattjes, Mike P.; Lammertsma, Adriaan A.; Boellaard, Ronald; Berckel, Bart N.M. van; Barkhof, Frederik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Pijnenburg, Yolande A.L.; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Kuijer, Joost P.A. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2015-10-15

    Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [{sup 18}F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-15

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

  19. Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Tatsuro; Itoh, Harumi [Department of Radiology, Fukui Medical University, Matsuoka (Japan); Sadato, Norihiro; Nishizawa, Sadahiko; Yonekura, Yoshiharu [Biomedical Imaging Research Center, Fukui Medical University (Japan)

    2002-02-01

    The aim of this study was to determine the effect of postprandial hyperglycaemia (HG) on the non-invasive measurement of cerebral metabolic rate of glucose (CMRGlc). Five patients who had a meal within an hour before a fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) examination were recruited in this study. They underwent intermittent arterial blood sampling (measured input function), and, based on this sampling, CMRGlc was calculated using an autoradiographic method (CMRGlc{sub real}). Simulated input functions were generated based on standardised input function, body surface area and net injected dose of FDG, and simulated CMRGlc (CMRGlc{sub sim}) was also calculated. Percent error of the area under the curve (AUC) between measured (AUC{sub real}) and simulated input function (AUC{sub IFsim}) and percent error between CMRGlc{sub real} and CMRGlc{sub sim} were calculated. These values were compared with those obtained from a previous study conducted under fasting conditions (F). The serum glucose level in the HG group was significantly higher than that in the F group (165{+-}69 vs 100{+-}9 mg/dl, P=0.0007). Percent errors of AUC and CMRGlc in grey matter and white matter in HG were significantly higher than those in F (12.9%{+-}1.3% vs 3.5%{+-}2.2% in AUC, P=0.0015; 18.2%{+-}2.2% vs 2.9%{+-}1.9% in CMRGlc in grey matter, P=0.0028; 24.0%{+-}4.6% vs 3.4%{+-}2.2% in CMRGlc in white matter, P=0.0028). It is concluded that a non-invasive method of measuring CMRGlc should be applied only in non-diabetic subjects under fasting conditions. (orig.)

  20. 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

  1. Towards a neurobiology of dysfunctional arousal in depression: the relationship between beta EEG power and regional cerebral glucose metabolism during NREM sleep.

    Science.gov (United States)

    Nofzinger, E A; Price, J C; Meltzer, C C; Buysse, D J; Villemagne, V L; Miewald, J M; Sembrat, R C; Steppe, D A; Kupfer, D J

    2000-04-10

    This study sought to clarify the neurobiological basis of variations in one aspect of central nervous system 'arousal' in depression by characterizing the functional neuroanatomic correlates of beta electroencephalographic (EEG) power density during non-rapid eye movement (NREM) sleep. First, nine healthy (n=9) subjects underwent concurrent EEG sleep studies and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans during their first NREM period of sleep in order to generate hypotheses about specific brain structures that show a relationship between increased beta power and increased relative glucose metabolism. Second, brain structures identified in the healthy subjects were then used as a priori regions of interest in similar analyses from identical studies in 12 depressed subjects. Statistical parametric mapping was used to identify the relationship between beta power and relative regional cerebral glucose metabolism (rCMRglu) during NREM sleep. Regions that demonstrated significant correlations between beta power and relative cerebral glucose metabolism in both the healthy and depressed subjects included the ventromedial prefrontal cortex and the right lateral inferior occipital cortex. During a baseline night of sleep, depressed patients demonstrated a trend toward greater beta power in relation to a separate age- and gender-matched healthy control group. In both healthy and depressed subjects, beta power negatively correlated with subjective sleep quality. Finally, in the depressed group, there was a trend for beta power to correlate with an indirect measure of absolute whole brain metabolism during NREM sleep. This study demonstrates a similar relationship between electrophysiological arousal and glucose metabolism in the ventromedial prefrontal cortex in depressed and healthy subjects. Given the increased electrophysiological arousal in some depressed patients and the known anatomical relations between the ventromedial

  2. Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory Performance in Community-Dwelling Older Adults.

    Science.gov (United States)

    Gardener, Samantha L; Sohrabi, Hamid R; Shen, Kai-Kai; Rainey-Smith, Stephanie R; Weinborn, Michael; Bates, Kristyn A; Shah, Tejal; Foster, Jonathan K; Lenzo, Nat; Salvado, Olivier; Laske, Christoph; Laws, Simon M; Taddei, Kevin; Verdile, Giuseppe; Martins, Ralph N

    2016-03-31

    Increasing evidence suggests that Alzheimer's disease (AD) sufferers show region-specific reductions in cerebral glucose metabolism, as measured by [18F]-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). We investigated preclinical disease stage by cross-sectionally examining the association between global cognition, verbal and visual memory, and 18F-FDG PET standardized uptake value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on differences between subjective memory complainers and non-memory complainers. The 18F-FDG PET regions of interest investigated include the hippocampus, amygdala, posterior cingulate, superior parietal, entorhinal cortices, frontal cortex, temporal cortex, and inferior parietal region. In the cohort as a whole, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in both the left hippocampus and right amygdala. There were no associations observed between global cognition, delayed recall in logical memory, or visual reproduction and 18F-FDG PET SUVR. Following stratification of the cohort into subjective memory complainers and non-complainers, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in the right amygdala in those with subjective memory complaints. There were no significant associations observed in non-memory complainers between 18F-FDG PET SUVR in regions of interest and cognitive performance. We observed subjective memory complaint-specific associations between 18F-FDG PET SUVR and immediate verbal memory performance in our cohort, however found no associations between delayed recall of verbal memory performance or visual memory performance. It is here argued that the neural mechanisms underlying verbal and visual memory performance may in fact differ in their pathways, and the characteristic reduction of 18F-FDG PET SUVR observed in this and previous studies likely reflects the pathophysiological changes in specific

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder.

    Science.gov (United States)

    Ramage, Amy E; Litz, Brett T; Resick, Patricia A; Woolsey, Mary D; Dondanville, Katherine A; Young-McCaughan, Stacey; Borah, Adam M; Borah, Elisa V; Peterson, Alan L; Fox, Peter T

    2016-02-01

    Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with (18)fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger- (n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R(2 )= 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R(2 )= 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context.

  8. 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.

  9. Differential regional cerebral glucose metabolism in clinical syndromes of frontotemporal lobar degeneration: a study with FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Park, J. M.; Cho, S. S.; Na, D. L.; Lee, K. H.; Choi, Y.; Choe, Y. S.; Kim, B. T.; Kim, S. E. [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    2001-07-01

    Frontotemporal lobar degeneration( FTLD) is the third most common dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neurobehavioral 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 patient with FTLD presented with four different clinical syndromes. We analysed 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. Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral premotor are 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 features of FTLD syndromes. These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD.

  10. 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.

  11. Uncoupling Protein 2 (UCP2) Function in the Brain as Revealed by the Cerebral Metabolism of (1-(13)C)-Glucose.

    Science.gov (United States)

    Contreras, Laura; Rial, Eduardo; Cerdan, Sebastian; Satrustegui, Jorgina

    2017-01-01

    The mitochondrial aspartate/glutamate transporter Aralar/AGC1/Slc25a12 is critically involved in brain aspartate synthesis, and AGC1 deficiency results in a drastic fall of brain aspartate levels in humans and mice. It has recently been described that the uncoupling protein UCP2 transports four carbon metabolites including aspartate. Since UCP2 is expressed in several brain cell types and AGC1 is mainly neuronal, we set to test whether UCP2 could be a mitochondrial aspartate carrier in the brain glial compartment. The study of the cerebral metabolism of (1-(13)C)-glucose in vivo in wild type and UCP2-knockout mice showed no differences in C3 or C2 labeling of aspartate, suggesting that UCP2 does not function as a mitochondrial aspartate carrier in brain. However, surprisingly, a clear decrease (of about 30-35 %) in the fractional enrichment of glutamate, glutamine and GABA was observed in the brains of UCP2-KO mice which was not associated with differences in either glucose or lactate enrichments. The results suggest that the dilution in the labeling of glutamate and its downstream metabolites could originate from the uptake of an unlabeled substrate that could not leave the matrix via UCP2 becoming trapped in the matrix. Understanding the nature of the unlabeled substrate and its precursor(s) as alternative substrates to glucose is of interest in the context of neurological diseases associated with UCP2.

  12. Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy.

    Science.gov (United States)

    Jeong, Jeong-Won; Asano, Eishi; Kumar Pilli, Vinod; Nakai, Yasuo; Chugani, Harry T; Juhász, Csaba

    2017-03-21

    To determine the spatial relationship between 2-deoxy-2[(18) F]fluoro-D-glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two-stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo- and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG-PET scans of 37 children with intractable epilepsy (31 with non-localizing MRI) were compared with age-matched pseudo-normal pediatric control PET data. Hypo-/hypermetabolic maps were transformed to 3D-MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG-defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface-distance analysis demonstrated that large portions of ECoG-defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18-0.25/0.94-0.90 for overlap 3-cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG-PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age-matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp, 2017. © 2017

  13. ''Ecstasy''-induced changes of cerebral glucose metabolism and their correlation to acute psychopathology. A 18-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Schreckenberger, M.; Sabri, O.; Arning, C.; Zimny, M.; Zeggel, T.; Wagenknecht, G.; Kaiser, H.J.; Buell, U. [Technische Hochschule Aachen (Germany). Klinik fuer Nuklearmedizin; Gouzoulis-Mayfrank, E.; Sass, H. [Technische Hochschule Aachen (Germany). Dept. of Psychiatry

    1999-12-01

    The aim of this study was to determine the acute effects of the 'Ecstasy' analogue MDE (3,4-methylene dioxyethamphetamine) on cerebral glucose metabolism (rMRGlu) of healthy volunteers and to correlate neurometabolism with acute psychopathology. In a radomized double-blind trial, 15 healthy volunteers without a history of drug abuse were examined with fluorine-18-deoxyglucose ({sup 18}FDG) positron emission tomography (PET) 110-120 min after oral administration of 2 mg/kg MDE (n=7) or placebo (n=8). Two minutes prior to radiotracer injection, constant cognitive stimulation was started and maintained for 32 min using a word repetition paradigm to ensure constant and comparable mental conditions during cerebral glucose uptake. Individual brain anatomy was represented using T1-weighted 3D flash magnetic resonance imaging (MRI), followed by manual regionalization into 108 regions of interest and PET/MRI overlay. After absolute quantification of rMR-Glu and normalization to global metabolism, normalized rMRGlu under MDE was compared to placebo using the Mann-Whitney U-test. Acute psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and rMRGlu was correlated to PANSS scores according to Spearman. MDE subjects showed 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, rMR-Glu 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). There were positive correlations between rMRGlu in the middle right cingulate and grandiosity (r=0.87; P<0.05), both the right amygadala (r=0.90, P<0.01) and the left posterior cingulate (r=0.90, P<0.01) to difficulties in abstract thinking, and the right frontal inferior (r=0.85, P<0.05), right anterior cingulate (r=0.93, P<0.01), and left anterior cingulate (r=0.85, P<0.05) to attentional deficits. A

  14. Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-(13)C]Glucose and [1,2-(13)C]Acetate as Substrates

    DEFF Research Database (Denmark)

    McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B;

    2016-01-01

    Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few c...

  15. Alterations in Cerebral Cortical Glucose and Glutamine Metabolism Precedes Amyloid Plaques in the APPswe/PSEN1dE9 Mouse Model of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Andersen, Jens V; Christensen, Sofie K; Aldana, Blanca I;

    2016-01-01

    Alterations in brain energy metabolism have been suggested to be of fundamental importance for the development of Alzheimer's disease (AD). However, specific changes in brain energetics in the early stages of AD are poorly known. The aim of this study was to investigate cerebral energy metabolism...

  16. Local cerebral glucose utilization during status epilepticus in newborn primates

    Energy Technology Data Exchange (ETDEWEB)

    Fujikawa, D.G.; Dwyer, B.E.; Lake, R.R.; Wasterlain, C.G.

    1989-06-01

    The effect of bicuculline-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) was studied in 2-wk-old ketamine-anesthetized marmoset monkeys, using the 2-(/sup 14/C)-deoxy-D-glucose autoradiographical technique. To estimate LCMRglc in cerebral cortex and thalamus during SE, the lumped constant (LC) for 2-deoxy-D-glucose (2-DG) and the rate constants for 2-DG and glucose were calculated for these regions. The control LC was 0.43 in frontoparietal cortex, 0.51 in temporal cortex, and 0.50 in thalamus; it increased to 1.07 in frontoparietal cortex, 1.13 in temporal cortex, and 1.25 in thalamus after 30 min of seizures. With control LC values, LCMRglc in frontoparietal cortex, temporal cortex, and dorsomedial thalamus appeared to increase four to sixfold. With seizure LC values, LCMRglc increased 1.5- to 2-fold and only in cortex. During 45-min seizures, LCMRglc in cortex and thalamus probably increases 4- to 6-fold initially and later falls to the 1.5- to 2-fold level as tissue glucose concentrations decrease. Together with our previous results demonstrating depletion of high-energy phosphates and glucose in these regions, the data suggest that energy demands exceed glucose supply. The long-term effects of these metabolic changes on the developing brain remain to be determined.

  17. Cerebral glucose utilization during stage 2 sleep in man.

    Science.gov (United States)

    Maquet, P; Dive, D; Salmon, E; Sadzot, B; Franco, G; Poirrier, R; Franck, G

    1992-01-31

    Using [18F]fluorodeoxyglucose method and positron emission tomography, we performed paired determinations of the cerebral glucose utilization at one week intervals during sleep and wakefulness, in 12 young normal subjects. During 6 of 28 sleep runs, a stable stage 2 SWS was observed that fulfilled the steady-state conditions of the model. The cerebral glucose utilization during stage 2 SWS was lower than during wakefulness, but the variation did not significantly differ from zero (mean variation: -11.5 +/- 25.57%, P = 0.28). The analysis of 89 regions of interest showed that glucose metabolism differed significantly from that observed at wake in 6 brain regions, among them both thalamic nuclei. We conclude that the brain energy metabolism is not homogeneous throughout all the stages of non-REMS but decreases from stage 2 SWS to deep SWS; we suggest that a low thalamic glucose metabolism is a metabolic feature common to both stage 2 and deep SWS, reflecting the inhibitory processes observed in the thalamus during these stages of sleep. Stage 2 SWS might protect the stability of sleep by insulating the subject from the environment and might be a prerequisite to the full development of other phases of sleep, especially deep SWS.

  18. 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.

  19. The significance of changes in cerebral oxygen and glucose metabolism in patients with cerebral hemorrhage caused by acute hypertension%急性高血压脑出血患者脑糖氧代谢变化及意义

    Institute of Scientific and Technical Information of China (English)

    马骏; 陈锷峰; 屠传建; 钱辉; 骆明; 顾志伟; 张建民

    2014-01-01

    Objective To study the clinical significance of early changes in cerebral oxygen and glucose metabolism in patients with cerebral hemorrhage and with Glasgow coma score (GCS) of 5-8 caused by acute hypertension in order to find relationship between those changes and prognosis.Methods From January 1,2011 to June 30,2012,a cohort of 43 patients with cerebral hemorrhage caused by acute hypertension were enrolled for retrospective study.Radial artery and internal jugular vein were separately cannulated retrogradely for collecting blood for blood gas analysis and blood glucose tests carried out 24 hours after the onset of the cerebral hemorrhage and then every 6-8 hours and as any major changes in physical signs of patients occurred.And this monitoring kept for consecutive 3 days.The data of these laboratory findings were analyzed and calculated to determine internal jugular vein oxygen saturation (SjVO2),cerebral oxygen utilization rate (CEO2),cerebral arterio-venous oxygen difference (AVDO2),arterio-venous blood glucose difference (V-Aglu),arterio-venous lactic acid difference (V-Alac) and absolute value of carbon dioxide pressure difference between jugular vein and artery (V-APCO2).All patients met the diagnostic criteria of hypertensive cerebral hemorrhage revised by the 4th National Academic Conference on cerebrovascular disease in 1995 requiring diagnosis confirmed by brain CT,admitted within 24 hours of onset,Glasgow coma score (GCS) 5-8 and a history of hypertension.Exclusion criteria were:cerebral hemorrhage caused by traumatic intracranial hematoma,spontaneous subarachnoid hemorrhage,arteriovenous malformation and Moyamoya disease,intracranial tumor apoplexy,cerebral bleeding derived from the disturbance of blood coagulation system,and cerebral hemorrhagic infarction.According to the short-term prognosis,the patients were divided into the death group and the survival group.Then the differences in biomarkers mentioned above between two groups were compared to

  20. Glucose metabolism and hyperglycemia.

    Science.gov (United States)

    Giugliano, Dario; Ceriello, Antonio; Esposito, Katherine

    2008-01-01

    Islet dysfunction and peripheral insulin resistance are both present in type 2 diabetes and are both necessary for the development of hyperglycemia. In both type 1 and type 2 diabetes, large, prospective clinical studies have shown a strong relation between time-averaged mean values of glycemia, measured as glycated hemoglobin (HbA1c), and vascular diabetic complications. These studies are the basis for the American Diabetes Association's current recommended treatment goal that HbA1c should be regulation is accompanied by a significant improvement of many pathways supposed to be involved in diabetic complications, including oxidative stress, endothelial dysfunction, inflammation, and nuclear factor-kappaB activation. The goal of therapy should be to achieve glycemic status as near to normal as safely possible in all 3 components of glycemic control: HbA1c, fasting glucose, and postmeal glucose peak.

  1. Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Rasmussen, Peter; Seifert, Thomas;

    2011-01-01

    Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose + 1/2 lactate) and metabolic acidosis appears to promote cerebral lactate uptake. However, the influence of pH on cerebral lactate uptake and, in turn, on the cerebral metabolic ratio during exercise is not known. Sodium.......05) following the Sal and Bicarb trials, respectively. Accordingly, the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials: from 5.8 ± 0.6 at rest to 1.7 ± 0.1 and 1.8 ± 0.2, respectively. The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis...

  2. Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic

    OpenAIRE

    Powers, William. J.; Videen, Tom O.; Markham, Joanne; Walter, Vonn; Perlmutter, Joel S.

    2011-01-01

    Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO2) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO2, CMRglc, and other covariates as predictors of resting ...

  3. 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.

  4. Cerebral energy metabolism during induced mitochondrial dysfunction

    DEFF Research Database (Denmark)

    Nielsen, T H; Bindslev, TT; Pedersen, S M

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  5. [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.

  6. 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.)

  7. Sex steroids and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Carolyn A Allan

    2014-04-01

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

  8. 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

  9. HDL and glucose metabolism: current evidence and therapeutic potential.

    Science.gov (United States)

    Siebel, Andrew L; Heywood, Sarah Elizabeth; Kingwell, Bronwyn A

    2015-01-01

    High-density lipoprotein (HDL) and its principal apolipoprotein A-I (ApoA-I) have now been convincingly shown to influence glucose metabolism through multiple mechanisms. The key clinically relevant observations are that both acute HDL elevation via short-term reconstituted HDL (rHDL) infusion and chronically raising HDL via a cholesteryl ester transfer protein (CETP) inhibitor reduce blood glucose in individuals with type 2 diabetes mellitus (T2DM). HDL may mediate effects on glucose metabolism through actions in multiple organs (e.g., pancreas, skeletal muscle, heart, adipose, liver, brain) by three distinct mechanisms: (i) Insulin secretion from pancreatic beta cells, (ii) Insulin-independent glucose uptake, (iii) Insulin sensitivity. The molecular mechanisms appear to involve both direct HDL signaling actions as well as effects secondary to lipid removal from cells. The implications of glucoregulatory mechanisms linked to HDL extend from glycemic control to potential anti-ischemic actions via increased tissue glucose uptake and utilization. Such effects not only have implications for the prevention and management of diabetes, but also for ischemic vascular diseases including angina pectoris, intermittent claudication, cerebral ischemia and even some forms of dementia. This review will discuss the growing evidence for a role of HDL in glucose metabolism and outline related potential for HDL therapies.

  10. Regional cerebral glucose utilization during morphine withdrawal in the rat.

    OpenAIRE

    Wooten, G.F.; DiStefano, P.; Collins, R. C.

    1982-01-01

    Regional cerebral glucose utilization was studied by 2-deoxy[14C]glucose autoradiography in morphine-dependent rats and during naloxone-induced morphine withdrawal. In morphine-dependent rats, glucose utilization was increased compared with naive controls uniformly (23-54%) in hippocampus, dentate gyrus, and subiculum and reduced in frontal cortex, striatum, anterior ventral thalamus, and medial habenular nucleus. On precipitation of morphine withdrawal by subcutaneous administration of nalox...

  11. Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Thomsen, Gerda;

    2002-01-01

    BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates...... to baseline ventilation, whereas CMR(glu) increased. CONCLUSION: In patients with acute bacterial meningitis, we found variable levels of CBF and cerebrovascular CO(2) reactivity, a low a-v DO(2), low cerebral metabolic rates of oxygen and glucose, and a cerebral lactate efflux. In these patients...

  12. Early evaluation of cerebral metabolic rate of glucose (CMRglu) with {sup 18}F-FDG PET/CT and clinical assessment in idiopathic normal pressure hydrocephalus (INPH) patients before and after ventricular shunt placement: preliminary experience

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Maria Lucia; Lavalle, Mariadea; Leccisotti, Lucia; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Institute of Nuclear Medicine, Rome (Italy); Mangiola, Annunziato; De Bonis, Pasquale; Anile, Carmelo [Universita Cattolica del Sacro Cuore, Institute of Neurosurgery, Rome (Italy); Indovina, Luca [Universita Cattolica del Sacro Cuore, Institute of Physics, Rome (Italy); Marra, Camillo [Universita Cattolica del Sacro Cuore, Institute of Neurology, Rome (Italy); Pelliccioni, Armando [Istituto Nazionale per l' Assicurazione contro gli Infortuni sul Lavoro (INAIL), Rome (Italy)

    2012-02-15

    We evaluated the relationships between the cerebral metabolic rate of glucose (CMRglu) measured by dynamic {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the clinical and neuropsychological assessment before and after the surgical procedure in idiopathic normal pressure hydrocephalus (INPH) patients. Eleven selected INPH patients underwent clinical assessment (modified Rankin scale, Krauss scale, Larsson categorization system and Stein-Langfitt scale), cognitive evaluation (Mini-Mental State Examination, MMSE) and dynamic {sup 18}F-FDG PET/CT scan 3 days before and 1 week after ventricular shunt placement. After shunting, the global CMRglu significantly increased (2.95 {+-} 0.44 vs 4.38 {+-} 0.68, p = 10{sup -7}) in all INPH patients with a mean percentage value of 48.7%. After shunting, no significant change was found in the Evans ratio whereas a significant decrease in all clinical scale scores was observed. Only a slight reduction in the MMSE was found. After shunting, a significant correlation between the global CMRglu value and clinical assessment was found (R {sup 2} = 0.75, p = 0.024); indeed all clinical scale scores varied (decreasing) and the CMRglu value also varied (increasing) in all INPH patients. Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of ''neuronal plasticity'' and for the cells' reactivity in order to recover their metabolic function. (orig.)

  13. Purine Metabolism in Acute Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ye. V. Oreshnikov

    2008-01-01

    Full Text Available Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

  14. 脑血管重度狭窄患者脑代谢与脑血流损害特点初步研究%Initial research on the damaged characteristics of cerebral glucose metabolism and cerebral blood flow in patients with severe cerebral artery stenosis

    Institute of Scientific and Technical Information of China (English)

    崔璨; 马云川; 王曼; 苏玉盛; 彭程; 张琳瑛; 刘亭廷; 尚建文; 仇英

    2014-01-01

    目的:探讨脑血管重度狭窄或闭塞患者脑葡萄糖代谢与脑血流灌注的受损特点。方法采用18F-FDG和13N-Ammonia PET联合脑显像,对33例缺血性脑血管病(ICVD)患者进行检查,获得同期脑葡萄糖代谢和脑血流灌注影像。经半定量分析,得到脑代谢减低率、脑血流减低率和脑代谢/脑血流比值。结果①共发现病灶121个,18F-FDG显像阳性率为91.7%,13N-Ammonia显像阳性率为78.5%。②ICVD病灶呈多灶性和不对称性分布。③根据两种影像的匹配性,将病灶分为两大类(5种类型):匹配型(I型)病灶66个,占54.5%;不匹配型(II型~V型)病灶55个,占45.5%。④以脑代谢/脑血流比值为指标,匹配型病灶的比值为1.10±0.13;不匹配型病灶比值增高组的95%CI为1.28~1.56,比值减低组的95%CI为0.95~1.08。将脑代谢/脑血流比值1.1~1.3作为区分匹配型与不匹配型的标准。⑤以脑代谢减低率和脑血流减低率为指标,将66个匹配型病灶分为轻度、中度、重度受损3组,各组之间的脑代谢、脑血流减低率差异均有统计学意义(χ2=56.854和56.800,P均<0.01)。其中,轻度受损病灶27个,占40.9%;中度受损病灶15个病灶,占22.7%;重度受损病灶24个,占36.4%。⑥4例单侧脑内病变者可见交叉性小脑失联络。结论脑血管重度狭窄患者脑代谢与脑血流的匹配关系明显受损,但其中存在着不同程度的脑代谢与脑血流损害;脑代谢-脑血流联合PET显像在脑血管重度狭窄患者脑损伤程度的评估中具有重要意义和应用价值。%Objective To investigate the damaged characteristics of cerebral glucose metabolism (CGM)and cerebral blood flow (CBF)in ischemic cerebrovascular disease (ICVD)patients with severe cerebral artery stenosis or occlusion. Methods Thirty-three cases of ICVD patients were examined by 18F-FDG PET and 13N

  15. Investigations on the effects of ``Ecstasy`` on cerebral glucose metabolism: an 18-FDG PET study; Untersuchungen zum Einfluss von ``Ecstasy`` auf den zerebralen Glukosemetabolismus: eine 18-FDG-PET-Studie

    Energy Technology Data Exchange (ETDEWEB)

    Schreckenberger, M.; Sabri, O.; Arning, C.; Tuttass, T.; Schulz, G.; Kaiser, H.J.; Wagenknecht, G.; Buell, U. [Klinik fuer Nuklearmedizin, Universitaetsklinik, RWTH Aachen (Germany); Gouzoulis-Mayfrank, E.; Sass, H. [Klinik fuer Psychiatrie, Universitaetsklinikum, RWTH Aachen (Germany)

    1998-12-31

    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 {mu}mol/min/100 g, placebo: 50,1{+-}18,1 {mu}mol/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.) [Deutsch] Ziel: In der vorliegenden Studie sollte die Akutwirkung des `Ecstasy`-Analogons MDE (3,4-Methylendioxyethamphetamin) auf den zentralen Glukosemetabolismus (rMRGlu) gesunder Probanden untersucht werden. Methode: In einer randomisierten

  16. Relationship between cerebral sodium-glucose transporter and hyperglycemia in cerebral ischemia.

    Science.gov (United States)

    Yamazaki, Yui; Harada, Shinichi; Tokuyama, Shogo

    2015-09-14

    Post-ischemic hyperglycemia exacerbates the development of cerebral ischemia. To elucidate this exacerbation mechanism, we focused on sodium-glucose transporter (SGLT) as a mediator that lead hyperglycemia to cerebral ischemia. SGLT transport glucose into the cell, together with sodium ion, using the sodium concentration gradient. We have previously reported that suppression of cerebral SGLT ameliorates cerebral ischemic neuronal damage. However, detail relationship cerebral between SGLT and post-ischemic hyperglycemia remain incompletely defined. Therefore, we examined the involvement of cerebral SGLT on cerebral ischemic neuronal damage with or without hyperglycemic condition. Cell survival rate of primary cultured neurons was assessed by biochemical assay. A mouse model of focal ischemia was generated using a middle cerebral artery occlusion (MCAO). Neuronal damage was assessed with histological and behavioral analyses. Concomitant hydrogen peroxide/glucose treatment exacerbated hydrogen peroxide alone-induced cell death. Although a SGLT family-specific inhibitor, phlorizin had no effect on developed hydrogen peroxide alone-induced cell death, it suppressed cell death induced by concomitant hydrogen peroxide/glucose treatment. α-MG induced a concentration-dependent and significant decrease in neuronal survival. PHZ administered on immediately after reperfusion had no effect, but PHZ given at 6h after reperfusion had an effect. Our in vitro study indicates that SGLT is not involved in neuronal cell death in non-hyperglycemic condition. We have already reported that post-ischemic hyperglycemia begins to develop at 6h after MCAO. Therefore, current our in vivo study show post-ischemic hyperglycemic condition may be necessary for the SGLT-mediated exacerbation of cerebral ischemic neuronal damage.

  17. One-year follow-up of neuropsychology, MRI, rCBF and glucose metabolism (rMRGlu) in cerebral microangiopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sabri, O.; Hellwig, D.; Schreckenberger, M.; Kaiser, H.-J.; Wagenknecht, G.; Setani, K.; Reinartz, P.; Zimny, M.; Buell, U. [Department of Nuclear Medicine, Technische Univ. Aachen (Germany); Schneider, R. [Department of Neurology, Technische Univ. Aachen (Germany); Mull, M. [Department of Neuroradiology, Technische Univ. Aachen (Germany); Ringelstein, E.-B. [Department of Neurology, Muenster Univ. (Germany)

    2000-07-01

    Background: MRI shows lacunar infarctions (LI), deep white matter lesions (DWML) and atrophy in cerebral microangiopathy, which is said to lead to vascular dementia. In a first trial series on 57 patients with confirmed pure cerebral microangiopathy (without concomitant macroangiopathy), neuropsychological impairment and (where present) brain atrophy correlated with decreased rCBF and rMRGlu. LI and DWML did not correlate with either neuropsychological impairment or decreased rCBF/rMRGlu. This study was done one year later to detect changes in any of the study parameters. Methods: 26 patients were re-examined for rCBF, rMRGlu, LI, DWML, atrophy and neuropsychological performance (7 cognitive, 3 mnestic, 4 attentiveness tests). Using a special head holder for exact repositioning, rCBF (SPECT) and rMRGlu (PET) were measured and imaged slice by slice. White matter/cortex were quantified using MRI-defined ROIs. Results: After one year the patients did not show significant decreases in rCBF or rMRGlu either in cortex or in white matter (p>0.05), nor did any patient show LI, DWML or atrophy changes on MRI. There were no significant neuropsychological decreases (p>0.05). (orig.) [German] Ziel: In der MRT zeigen sich bei zerebraler Mikroangiopathie (ZMA) lakunaere Infarkte (LI), Deep White Matter Lesions (DWML) und Atrophie (Atr). Die sogenannte vaskulaere Demenz wurde dabei hauptsaechlich auf die Laesionen der weissen Substanz zurueckgefuehrt. In einer ersten Untersuchungsreihe waren bei 57 Patienten mit gesicherter ZMA nur neuropsychologische Defizite (Nps) und, falls vorhanden, Atr als Grundlage fuer erniedrigte rCBF/rMRGlu-Werte zu eruieren, jedoch nicht LI/DWML. Es sollte geklaert werden, ob sich im Verlauf der Erkrankung nach einem Jahr Veraenderungen dieser Parameter ergeben. Methode: 26 Patienten wurden nach einem Jahr erneut neuropsychologisch untersucht (7 kognitive, 3 mnestrische, 4 Aufmerksamkeitstests). Mittels eines speziellen Kopfhalterungssystems wurden in

  18. Glucose metabolism in rat retinal pigment epithelium.

    Science.gov (United States)

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress.

  19. Complementary acupuncture treatment increases cerebral metabolism in patients with Parkinson's disease.

    Science.gov (United States)

    Huang, Yong; Jiang, Xuemei; Zhuo, Ying; Tang, Anwu; Wik, Gustav

    2009-01-01

    We used positron emission tomography (PET) and the 18-flourodeoxyglucose tracer to study cerebral effects of complementary acupuncture in Parkinson's disease. Five patients received scalp-acupuncture and Madopa, while the other five had Madopa only. PET scans before and after 5 weeks of complementary acupuncture treatment show increased glucose metabolisms in parietal, temporal, occipital lobes, the thalamus, and the cerebellum in the light-diseased hemisphere, and in parietal and occipital lobes of the severe-diseased hemisphere. No changes were observed in the Madopa-only group. Acupuncture in combination with Madopa may improve cerebral glucose metabolism in Parkinson's disease.

  20. PET measurements of cerebral metabolism corrected for CSF contributions

    Energy Technology Data Exchange (ETDEWEB)

    Chawluk, J.; Alavi, A.; Dann, R.; Kushner, M.J.; Hurtig, H.; Zimmerman, R.A.; Reivich, M.

    1984-01-01

    Thirty-three subjects have been studied with PET and anatomic imaging (proton-NMR and/or CT) in order to determine the effect of cerebral atrophy on calculations of metabolic rates. Subgroups of neurologic disease investigated include stroke, brain tumor, epilepsy, psychosis, and dementia. Anatomic images were digitized through a Vidicon camera and analyzed volumetrically. Relative areas for ventricles, sulci, and brain tissue were calculated. Preliminary analysis suggests that ventricular volumes as determined by NMR and CT are similar, while sulcal volumes are larger on NMR scans. Metabolic rates (18F-FDG) were calculated before and after correction for CSF spaces, with initial focus upon dementia and normal aging. Correction for atrophy led to a greater increase (%) in global metabolic rates in demented individuals (18.2 +- 5.3) compared to elderly controls (8.3 +- 3.0,p < .05). A trend towards significantly lower glucose metabolism in demented subjects before CSF correction was not seen following correction for atrophy. These data suggest that volumetric analysis of NMR images may more accurately reflect the degree of cerebral atrophy, since NMR does not suffer from beam hardening artifact due to bone-parenchyma juxtapositions. Furthermore, appropriate correction for CSF spaces should be employed if current resolution PET scanners are to accurately measure residual brain tissue metabolism in various pathological states.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    Background:Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors.This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types.Methods:One hundred and twenty patients with primary untreated lung cancer,who visited People's Hospital of Zhengzhou University from February 2012 to July 2013,were divided into three groups based on histological types confirmed by biopsy or surgical pathology,which included adenocarcinoma (52 cases),squamous cell carcinoma (43 cases),and small-cell carcinoma (25 cases).The whole body 18F-fluorodeoxyglucose (1 8F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied.The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software,with 50 age-matched and gender-matched healthy controls for comparison.Results:The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction.The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal,bilateral superior and middle temporal and inferior and middle temporal gyrus.Besides,the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group.The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292).Conclusions:The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  2. Improved cerebral energetics and ketone body metabolism in db/db mice.

    Science.gov (United States)

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D; Waagepetersen, Helle S

    2017-03-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate for cerebral glucose hypometabolism and unravel the functionality of cerebral mitochondria in type 2 diabetes mellitus. Acutely isolated cerebral cortical and hippocampal slices of db/db mice were incubated in media containing [U-(13)C]glucose, [1,2-(13)C]acetate or [U-(13)C]β-hydroxybutyrate and tissue extracts were analysed by mass spectrometry. Oxygen consumption and ATP synthesis of brain mitochondria of db/db mice were assessed by Seahorse XFe96 and luciferin-luciferase assay, respectively. Glucose hypometabolism was observed for both cerebral cortical and hippocampal slices of db/db mice. Significant increased metabolism of [1,2-(13)C]acetate and [U-(13)C]β-hydroxybutyrate was observed for hippocampal slices of db/db mice. Furthermore, brain mitochondria of db/db mice exhibited elevated oxygen consumption and ATP synthesis rate. This study provides evidence of several changes in brain energy metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism.

  3. Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas; Balchen, T; Bruhn, T;

    1999-01-01

    A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral...

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

    NARCIS (Netherlands)

    Teune, Laura K.; Renken, Remco J.; de Jong, Bauke M.; Willemsen, Antoon T.; van Osch, Matthias J.; Roerdink, Jos B. T. M.; Dierckx, Rudi A.; Leenders, Klaus L.

    2014-01-01

    INTRODUCTION: Under normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfu

  5. 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)

  6. Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets

    DEFF Research Database (Denmark)

    Nielsen, Troels Halfeld; Olsen, N.V.; Toft, P;

    2013-01-01

    variables related to energy metabolism. METHODS: Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2 ) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis...... metabolism and degradation of cellular membranes, respectively. CONCLUSION: Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2 . The condition is biochemically characterised by a marked increase in cerebral lactate...... with a normal or elevated pyruvate level. The metabolic pattern is different from cerebral ischemia, which is characterised by simultaneous decreases in intracerebral pyruvate and PbtO2 . The study supports the hypothesis that cerebral ischemia and mitochondrial dysfunction may be identified and separated...

  7. 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.

  8. Melatonin and glucose metabolism: clinical relevance.

    Science.gov (United States)

    Lardone, P J; Alvarez-Sanchez, Sanchez N; Guerrero, J M; Carrillo-Vico, A

    2014-01-01

    The role of melatonin in glucose homeostasis is an active area of investigation. There is a growing body of evidence suggesting a link between disturbances in melatonin production and impaired insulin, glucose, lipid metabolism, and antioxidant capacity. Furthermore, melatonin has been found to influence insulin secretion both in vivo and in vitro, and night-time melatonin levels are related to night-time insulin concentrations in patients with diabetes. In several recent studies, a single nucleotide polymorphism of the human melatonin receptor 1B has been described as being causally linked to an increased risk of developing type 2 diabetes. Taken together, these data suggest that endogenous as well as exogenous melatonin may play a role in diabetes and associated metabolic disturbances not only by regulating insulin secretion but also by providing protection against reactive oxygen species, considering pancreatic β-cells are particularly susceptible to oxidative stress because they possess only low-antioxidative capacity.

  9. Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices

    Directory of Open Access Journals (Sweden)

    Torres I.L.S.

    2001-01-01

    Full Text Available It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 µCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

  10. Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals

    DEFF Research Database (Denmark)

    Fisher, James P; Hartwich, Doreen; Seifert, Thomas

    2013-01-01

    artery blood velocity (MCA V(mean)), mean arterial pressure (MAP), cardiac output (CO) and the partial pressure of arterial carbon dioxide (PaCO(2)) were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O(2......)), glucose and lactate across the brain. The molar ratio between the cerebral uptake of O(2) versus carbohydrate (O(2)-carbohydrate index; O(2) / [glucose + 0.5 lactate]; OCI), the cerebral metabolic rate of O(2) (CMRO(2)) and changes in mitochondrial O(2) tension (P(mito)O(2)) were calculated. W...

  11. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  12. Cerebral blood flow and metabolism during sleep.

    Science.gov (United States)

    Madsen, P L; Vorstrup, S

    1991-01-01

    A review of the current literature regarding sleep-induced changes in cerebral blood flow (CBF) and cerebral metabolic rate (CMR) is presented. Early investigations have led to the notion that dreamless sleep was characterized by global values of CBF and CMR practically at the level of wakefulness, while rapid eye movement (REM) sleep (dream sleep) was a state characterized by a dramatically increased level of CBF and possibly also of CMR. However, recent investigations firmly contradict this notion. Investigations on CBF and CMR performed during non-REM sleep, taking the effect of different levels of sleep into consideration, show that light sleep (stage II) is characterized by global levels of CBF and CMR only slightly reduced by 3-10% below the level associated with wakefulness, whereas CBF and CMR during deep sleep (stage III-IV) is dramatically reduced by 25-44%. Furthermore, recent data indicate that global levels of CBF and CMR are about the same during REM sleep as in wakefulness. On the regional level, deep sleep seems to be associated with a uniform decrease in regional CBF and CMR. Investigations concerning regional CBF and CMR during REM sleep are few but data from recent investigations seem to identify site-specific changes in regional CBF and CMR during REM sleep. CBF and CMR are reflections of cerebral synaptic activity and the magnitude of reduction in these variables associated with deep sleep indicates that overall cerebral synaptic activity is reduced to approximately one-half the level associated with wakefulness, while cerebral synaptic activity levels during REM sleep are similar to wakefulness. However, even though the new understanding of CBF and CMR during sleep provides significant and important information of the brain's mode of working during sleep, it does not at its current state identify the physiological processes involved in sleep or the physiological role of sleep.

  13. Activation-induced resetting of cerebral oxygen and glucose uptake in the rat

    DEFF Research Database (Denmark)

    Madsen, P L; Linde, R; Hasselbalch, S G;

    1998-01-01

    In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose...... and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize...

  14. Relationship Between HbAlc Levels and Cerebral Arterial Lesions in Patients With Ischemic Stroke With Different Glucose Metabolism%不同糖代谢状况缺血性脑卒中患者HbAlc水平与脑动脉病变程度的关系

    Institute of Scientific and Technical Information of China (English)

    詹红艳; 杨红英; 袁莉; 牛春华; 王丽英; 陈丽丽

    2015-01-01

    ObjectiveTo study the relationship between the level of glycosylated hemoglobin and cerebral arterial lesions in patients with ischemic stroke with different glucose metabolism.Methods 120 cases of ischemic stroke patients were chosen from June 2013 to June 2015 in Tangshan workers hospital, according to glucose metabolism is divided into normal group (n=20) and abnormal group (n=65), diabetes group (n=35). To analysis of HbA1c level, risk factors for cerebral artery disease, cerebral artery lesion sites and count of the three groups were compared. ResultsThere were no significant differences in gender, hypertension, smoking, TG, Hcy among the three groups (P>0.05), the differences were statistically signiifcant with alcohol, coronary heart disease, TC, HDL-C, HbAlc, LDL-C In the three groups of patients (P<0.05). In the patients with abnormal glucose metabolism and diabetes mellitus, cerebral blood vessel stenosis was dominated by moderate and severe cerebral artery stenosis, and the main was the main and the most affected (P<0.05).Conclusion Different levels of glucose metabolism affect cerebral vascular lesions and HbAlc level of cerebral artery stenosis, the location of the lesion and lesion count is affect brain artery disease are important risk factors.%目的研究不同糖代谢状况缺血性脑卒中患者的糖化血红蛋白水平与脑动脉病变程度的关系。方法选取2013年6月~2015年6月唐山市工人医院收治的缺血性脑卒中患者120例,根据糖代谢情况分为正常组(n=20)、异常组(n=65)、糖尿病组(n=35),比较三组的一般资料、分析HbAlc水平、脑动脉病变危险因素、脑动脉病变部位及支数。结果三组患者性别、高血压、吸烟、TG、Hcy等方面比较,差异无统计学意义(P>0.05),三组患者中饮酒、冠心病、HbAlc、TC、HDL-C、LDL-C比较,差异有统计学意义(P<0.05);三组患者中,正常组脑血管狭窄以轻度为主,

  15. Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose method.

    Science.gov (United States)

    Maquet, P; Dive, D; Salmon, E; Sadzot, B; Franco, G; Poirrier, R; von Frenckell, R; Franck, G

    1990-04-09

    Using the [18F]fluorodeoxyglucose method and positron emission tomography, we studied cerebral glucose utilization during sleep and wakefulness in 11 young normal subjects. Each of them was studied at least thrice: during wakefulness, slow wave sleep (SWS) and rapid eye movement sleep (REMS), at 1 week intervals. Four stage 3-4 SWS and 4 REMS fulfilled the steady state conditions of the model. The control population consisted of 9 normal age-matched subjects studied twice during wakefulness at, at least, 1 week intervals. Under these conditions, the average difference between the first and the second cerebral glucose metabolic rates (CMRGlu was: -7.91 +/- 15.46%, which does not differ significantly from zero (P = 0.13). During SWS, a significant decrease in CMRGlu was observed as compared to wakefulness (mean difference: -43.80 +/- 14.10%, P less than 0.01). All brain regions were equally affected but thalamic nuclei had significantly lower glucose utilization than the average cortex. During REMS, the CMRGlu were as high as during wakefulness (mean difference: 4.30 +/- 7.40%, P = 0.35). The metabolic pattern during REMS appeared more heterogeneous than at wake. An activation of left temporal and occipital areas is suggested. It is hypothetized that energy requirements for maintaining membrane polarity are reduced during SWS because of a decreased rate of synaptic events. During REMS, cerebral glucose utilization is similar to that of wakefulness, presumably because of reactivated neurotransmission and increased need for ion gradients maintenance.

  16. Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic.

    Science.gov (United States)

    Powers, William J; Videen, Tom O; Markham, Joanne; Walter, Vonn; Perlmutter, Joel S

    2011-05-01

    Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO(2)) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO(2), CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO(2) was a significant predictor of CBF. The final multivariate model contained two additional terms in addition to CMRO(2): arterial oxygen content and oxygen extraction fraction. Notably, arterial plasma glucose concentration and CMRglc were not included in the final model. Our data demonstrate that the metabolic factor controlling hemispheric CBF in the normal resting brain is CMRO(2) and that CMRglc does not make a contribution. Our findings provide evidence for compartmentalization of brain metabolism into a basal component in which CBF is coupled to oxygen metabolism and an activation component in which CBF is controlled by another mechanism.

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic...

  18. Metabolic fate of extracted glucose in normal human myocardium.

    OpenAIRE

    Wisneski, J A; Gertz, E W; Neese, R A; Gruenke, L D; D. L. Morris; Craig, J. C.

    1985-01-01

    Glucose is an important substrate for myocardial metabolism. This study was designed to determine the effect of circulating metabolic substrates on myocardial glucose extraction and to determine the metabolic fate of glucose in normal human myocardium. Coronary sinus and arterial catheters were placed in 23 healthy male volunteers. [6-14C]Glucose was infused as a tracer in 10 subjects. [6-14C]Glucose and [U-13C]lactate were simultaneously infused in the other 13 subjects. Simultaneous blood s...

  19. 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...

  20. Characterization of cerebral glucose dynamics in vivo with a four-state conformational model of transport at the blood-brain barrier.

    Science.gov (United States)

    Duarte, João M N; Gruetter, Rolf

    2012-05-01

    Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state conformational model of glucose transport than with any of the other models tested. Furthermore, we confirmed the utility of the present method to determine glucose transport and consumption by analysing the modulation of both glucose transport and consumption by anaesthesia conditions that modify cerebral activity. In particular, deep thiopental anaesthesia caused a significant reduction of both T(max) and cerebral metabolic rate for glucose consumption. In conclusion, dynamic measurement of brain glucose in vivo in function of plasma glucose allows robust determination of both glucose uptake and consumption kinetics.

  1. The effect of herbs on cerebral energy metabolism in cerebral ischemia-reperfusion mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Vascular dementia is one of the most familiar types of senile dementia. Over the past few years, the research on the damage of cerebral tissues after ischemia has become a focus. The factors and mechanism of cerebral tissue damage after ischemia are very complex. The handicap of energy metabolism is regarded as the beginning factor which leads to the damage of neurons, but its dynamic changes in ischemic area and its role during the process of neuronal damage are not very clear. There are few civil reports on using 31 P nuclear magnetic resonance instrument to explore the changes of cerebral energy metabolism in intravital animals. After exploring the influence of herbs on cerebral energy metabolism in ischemia-reperfusion mice, we came to the conclusion that herbs can improve the cerebral energy metabolism in ischemia-reperfusion mice.

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

  3. Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Møller, Kirsten; Volianitis, Stefanos

    2002-01-01

    The development of hyperthermia during prolonged exercise in humans is associated with various changes in the brain, but it is not known whether the cerebral metabolism or the global cerebral blood flow (gCBF) is affected. Eight endurance-trained subjects completed two exercise bouts on a cycle...... ergometer. The gCBF and cerebral metabolic rates of oxygen, glucose, and lactate were determined with the Kety-Schmidt technique after 15 min of exercise when core temperature was similar across trials, and at the end of exercise, either when subjects remained normothermic (core temperature = 37.9 degrees C...... with control at the end of exercise (43 +/- 4 vs. 51 +/- 4 ml. 100 g(-1). min(-1); P

  4. Simultaneous Voltammetric Measurements of Glucose and Dopamine Demonstrate the Coupling of Glucose Availability with Increased Metabolic Demand in the Rat Striatum.

    Science.gov (United States)

    Smith, Samantha K; Lee, Christie A; Dausch, Matthew E; Horman, Brian M; Patisaul, Heather B; McCarty, Gregory S; Sombers, Leslie A

    2017-02-15

    Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain. This work evaluates several waveforms to enable the first simultaneous detection of endogenous glucose and dopamine at single recording sites. These molecules, one electroactive and one nonelectroactive, were found to fluctuate in the dorsal striatum in response to electrical stimulation of the midbrain and systemic infusion of cocaine/raclopride. The data reveal the second-by-second dynamics of these species in a striatal microenvironment, and directly demonstrate the coupling of glucose availability with increased metabolic demand. This work provides a foundation that will enable detailed investigation of local mechanisms that regulate the coupling of cerebral blood flow with metabolic demand under normal conditions, and in animal studies of drug abuse and addiction.

  5. In vivo measurements of brain glucose transport using the reversible Michaelis-Menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia.

    Science.gov (United States)

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

    2001-06-01

    Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood-brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in alpha-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma glucose, which is consistent with the reversible Michaelis-Menten model. When the model was fitted to the brain glucose measurements, the apparent Michaelis-Menten constant, Kt, was 3.3 +/- 1.0 mmol/L, and the ratio of the maximal transport rate relative to CMRglc, Tmax/CMRglc, was 2.7 +/- 0.1. This Kt is comparable to the authors' previous human data, suggesting that glucose transport kinetics in humans and rats are similar. Cerebral blood flow (CBF) was simultaneously assessed and constant above 2 mmol/L plasma glucose at 73 +/- 6 mL 100 g(-1) min(-1). Extrapolation of the reversible Michaelis-Menten model to hypoglycemia correctly predicted the plasma glucose concentration (2.1 +/- 0.6 mmol/L) at which brain glucose concentrations approached zero. At this point, CBF increased sharply by 57% +/- 22%, suggesting that brain glucose concentration is the signal that triggers defense mechanisms aimed at improving glucose delivery to the brain during hypoglycemia.

  6. Persistent impaired glucose metabolism in a zebrafish hyperglycemia model.

    Science.gov (United States)

    Capiotti, Katiucia Marques; Antonioli, Régis; Kist, Luiza Wilges; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

    2014-05-01

    Diabetes mellitus (DM) affects over 10% of the world's population. Hyperglycemia is the main feature for the diagnosis of this disease. The zebrafish (Danio rerio) is an established model organism for the study of various metabolic diseases. In this paper, hyperglycemic zebrafish, when immersed in a 111 mM glucose solution for 14 days, developed increased glycation of proteins from the eyes, decreased mRNA levels of insulin receptors in the muscle, and a reversion of high blood glucose level after treatment with anti-diabetic drugs (glimepiride and metformin) even after 7 days of glucose withdrawal. Additionally, hyperglycemic zebrafish developed an impaired response to exogenous insulin, which was recovered after 7 days of glucose withdrawal. These data suggest that the exposure of adult zebrafish to high glucose concentration is able to induce persistent metabolic changes probably underlined by a hyperinsulinemic state and impaired peripheral glucose metabolism.

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ratib, O.; Phelps, M.E.; Huang, S.C.; Henze, E.; Selin, C.E.; Schelbert, H.R.

    1981-01-01

    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.

  9. 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

    .29 +/- 0.01 g/g). The glucose metabolism of S. kluyveri was further characterized by the new and powerful techniques of metabolic network analysis. Flux distributions in the central carbon metabolism were estimated for respiro-fermentative growth in aerobic batch cultivation on glucose and respiratory...... at a constant specific rate of 0.12 g ethyl acetate per g dry weight per hour. The aerobic glucose metabolism in S. kluyveri was found to be less fermentative than in S. cerevisiae, as illustrated by the comparably low yield of ethanol on glucose (0.08 +/- 0.02 g/g), and high yield of biomass on glucose (0...... 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...

  10. 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.

  11. 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.

  12. Cerebral blood flow and metabolism during sleep

    DEFF Research Database (Denmark)

    Madsen, Peter Lund; Vorstrup, S

    1991-01-01

    investigations seem to identify site-specific changes in regional CBF and CMR during REM sleep. CBF and CMR are reflections of cerebral synaptic activity and the magnitude of reduction in these variables associated with deep sleep indicates that overall cerebral synaptic activity is reduced to approximately one......-half the level associated with wakefulness, while cerebral synaptic activity levels during REM sleep are similar to wakefulness. However, even though the new understanding of CBF and CMR during sleep provides significant and important information of the brain's mode of working during sleep, it does not at its...

  13. Visfatin, glucose metabolism and vascular disease: a review of evidence

    Directory of Open Access Journals (Sweden)

    Saddi-Rosa Pedro

    2010-03-01

    Full Text Available Abstract The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease.

  14. 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

  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.......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. Glucose metabolism in injured tissue: A longitudinal study

    Energy Technology Data Exchange (ETDEWEB)

    Daley, J.M.; Shearer, J.D.; Mastrofrancesco, B.; Caldwell, M.D. (Brown Univ., Providence, RI (USA))

    1990-02-01

    Injured tissue is characterized by increased glucose uptake and increased lactate production as compared to normal tissue. These metabolic changes have been attributed to the presence of inflammatory cells in injured tissues. To correlate these metabolic changes with changes in the inflammatory cell population at various times after injury, we studied the lambda-carrageenan hindlimb wound model in anesthetized rats. Perfusion studies demonstrated that at 3 and 5 days after injury glucose uptake was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. At 3, 5, and 10 days after injury, lactate production from glucose was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. These metabolic changes were not related to differences in body weight or food intake. There was no difference in glucose oxidation or in oxygen consumption in injured hindlimbs, compared with hindlimbs from pair-fed control animals. The increased glucose uptake and increased lactate production from glucose was coincident with the presence of inflammatory cells--predominantly macrophages--at the site of injury. It is suggested that the glucose metabolism in injured tissue reflects the metabolism of the inflammatory cells at the site of injury.

  17. Cerebral vascular control and metabolism in heat stress

    DEFF Research Database (Denmark)

    Bain, Anthony R; Nybo, Lars; Ainslie, Philip N

    2015-01-01

    in cerebral oxygen extraction. However, severe increases in whole-body and brain temperature may increase blood-brain barrier permeability, potentially leading to cerebral vasogenic edema. The cerebrovascular challenges associated with hyperthermia are of paramount importance for populations with compromised......This review provides an in-depth update on the impact of heat stress on cerebrovascular functioning. The regulation of cerebral temperature, blood flow, and metabolism are discussed. We further provide an overview of vascular permeability, the neurocognitive changes, and the key clinical...... implications and pathologies known to confound cerebral functioning during hyperthermia. A reduction in cerebral blood flow (CBF), derived primarily from a respiratory-induced alkalosis, underscores the cerebrovascular changes to hyperthermia. Arterial pressures may also become compromised because of reduced...

  18. 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

  19. Changes in cerebral glucose metabolism induced by postoperative delirium in elderly patients and the effects of dexmedetomidine on it%术后谵妄老年病人脑葡萄糖代谢的变化及右美托咪定对其影响

    Institute of Scientific and Technical Information of China (English)

    马昊; 欧阳文; 莫逸; 黎祖荣; 廖琴; 王懿春; 段开明; 陈明华; 廖炎

    2012-01-01

    Objective To investigate the changes in cerebral glucose metabolism induced by postoperative delirium in the elderly patients and the effects of dexmedetomidine on it.Methods Forty-two patients of both sexes aged 65-85 yr with a body mass index of 19-25 kg/m2 undergoing abdominal surgery under general anesthesia were enrolled in this study.Delirium occurred during the first 2 days after operation in 39 out of the 42 patients (29/42).The 29 patients were randomly divided into 2 groups:group delirium without any treatment (group D,n =13) and group delirium + dexmedetomidine (group Dex,n =16).The remaining 13 patients did not develop delirium after operation and served as control group (group C).In group Dex a loading dose of dexmedetomidine 1 μg/kg was administered iv over 10 min after occurrence of delirium followed by continuous infusion at 0.2-0.7μg· kg-1 · h-1.PET scan was performed within the time period in which delirium occurred.18 Fluorine-deoxyglucose was injected for observation of imaging of glucose metabolism.The standard uptake value of glucose of bilateral parietal,temporal and frontal lobes was calculated.Results Delirium was controlled within 30 min after adminnistration of dexmedetomidine.Delirium significantly reduced cerebral glucose metabolism in the bilateral parietal,temporal and frontal lobes in group D as compared with group C (P < 0.05).Dexmedetomidine significantly attenuated the delirium-induced decrease in cerebral glucose metabolic rate of the 3 lobes in group Dex as compared with group D (P < 0.05).Conclusion Postoperative delirium reduces cerebral glucose metabolism and dexmedetomidine can significantly control pastoperative delirium in the elderly patients.%目的 探讨术后谵妄老年病人脑葡萄糖代谢的变化及右美托咪定对其影响.方法 择期全麻下行腹部手术的老年病人,性别不限,BMI 19~ 25 kg/m2,年龄65~ 85岁,ASA分级Ⅰ或Ⅱ级.术后2d内评价谵妄的发生情况,将术后谵妄

  20. 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.

  1. Effects of central gastrin-releasing peptide on glucose metabolism

    NARCIS (Netherlands)

    Jha, Pawan Kumar; Foppen, Ewout; Challet, Etienne; Kalsbeek, A.

    2015-01-01

    Gastrin-releasing peptide (GRP) mediated signals in the central nervous system (CNS) influence many functions associated with energy metabolism. The purpose of the present study was to investigate the central effect of GRP on glucose metabolism in the male rat. Intracerebroventricular (icv) administ

  2. Cerebral blood flow and oxidative metabolism during human endotoxemia

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Qvist, Jesper;

    2002-01-01

    The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been suggested to mediate septic encephalopathy through an effect on cerebral blood flow (CBF) and metabolism. The effect of an intravenous bolus of endotoxin on global CBF, metabolism, and net flux of cytokines...... and catecholamines was investigated in eight healthy young volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique at baseline (during normocapnia and voluntary hyperventilation for calculation of subject-specific cerebrovascular CO reactivity), and 90 minutes after an intravenous bolus...

  3. 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

  4. Metabolic pattern of the acute phase of subarachnoid hemorrhage in a novel porcine model: studies with cerebral microdialysis with high temporal resolution.

    Directory of Open Access Journals (Sweden)

    Christoffer Nyberg

    Full Text Available BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed. OBJECTIVE: To study early cerebral energy changes in an animal model. METHODS: Experimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate. RESULTS: In nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia. CONCLUSION: The animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.

  5. Effects of Metformin on the Cerebral Metabolic Changes in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Yung-Cheng Huang

    2014-01-01

    Full Text Available Metformin, a widely used antidiabetic drug, has numerous effects on human metabolism. Based on emerging cellular, animal, and epidemiological studies, we hypothesized that metformin leads to cerebral metabolic changes in diabetic patients. To explore metabolism-influenced foci of brain, we used 2-deoxy-2-[18F]fluoro-D-glucose (FDG positron emission tomography for type 2 diabetic patients taking metformin (MET, n=18, withdrawing from metformin (wdMET, n=13, and not taking metformin (noMET, n=9. Compared with the noMET group, statistical parametric mapping showed that the MET group had clusters with significantly higher metabolism in right temporal, right frontal, and left occipital lobe white matter and lower metabolism in the left parahippocampal gyrus, left fusiform gyrus, and ventromedial prefrontal cortex. In volume of interest (VOI- based group comparisons, the normalized FDG uptake values of both hypermetabolic and hypometabolic clusters were significantly different between groups. The VOI-based correlation analysis across the MET and wdMET groups showed a significant negative correlation between normalized FDG uptake values of hypermetabolic clusters and metformin withdrawal durations and a positive but nonsignificant correlation in the turn of hypometabolic clusters. Conclusively, metformin affects cerebral metabolism in some white matter and semantic memory related sites in patients with type 2 diabetes.

  6. 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.

  7. 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.

  8. 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...

  9. Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Wildschiødtz, Gordon

    1991-01-01

    It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restriction...... associated with light anesthesia. During REM sleep (dream sleep) CMRO2 was practically the same as in the awake state. Changes in CBF paralleled changes in CMRO2 during both deep and REM sleep....... on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography....... Contrary to the only previous study in humans, which reported an insignificant 3% reduction in CMRO2 during sleep, we found a deep-sleep-associated statistically highly significant 25% decrease in CMRO2, a magnitude of depression according with studies of glucose uptake and reaching levels otherwise...

  10. Perturbed glucose metabolism: insights into Multiple Sclerosis pathogenesis

    Directory of Open Access Journals (Sweden)

    Deepali eMathur

    2014-12-01

    Full Text Available Multiple sclerosis (MS is a complex debilitating disease of the central nervous system perceived to result from the autoimmune effect of T cells in damaging myelin sheath. However, the exact pathogenesis of the disease remains elusive. Initial studies describing the possibility of defective pyruvate metabolism in MS were performed in 1950s. The group observed elevated blood pyruvate level in both fasting and postprandial times in MS patients with relapse. Similarly, other investigators also reported increased fasting pyruvate level in this disease. These reports hint to a possible abnormality of pyruvate metabolism in MS patients. In addition, increase in levels of Krebs cycle acids like alpha-ketoglutarate in fasting and citrate after glucose intake in MS patients further strengthened the connection of disturbed pyruvate metabolism with MS progression. These studies led the investigators to explore the role of disturbed glucose metabolism in pathophysiological brain function. Under normal circumstances, complex molecules are metabolized into simpler molecules through their respective pathways. Differential expression of genes encoding enzymes of the glucose metabolic pathway in central nervous system (CNS may result in neurological deficits. In this review article, we discussed the studies related to disturbed carbohydrate metabolism in MS and other neurodegenerative diseases. These observations open new perspectives for the understanding of metabolic dynamics in multiple sclerosis yet many puzzling aspects and critical questions need to be addressed. Much more research is required to fully unravel the disease mechanism, and a proper understanding of the disease could eventually lead to new treatments.

  11. 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....

  12. 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......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...

  13. Antilipolytic drug boosts glucose metabolism in prostate cancer

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. Cerebral blood flow and oxygen metabolism in the Rett syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Hideto; Fueki, Noboru; Suzuki, Hisaharu; Sakuragawa, Norio; Iio, Masaaki (National Central Hospital for Mental, Nervous and Muscular Disorders, Tokyo (Japan))

    1992-05-01

    Positron emission tomography (PET) was performed on six patients with the Rett syndrome and the results were compared with the concurrent clinical status of the patients. The cerebral metabolic rate of oxygen (CMRO{sub 2}) was low in five patients, and oxygen extraction fraction (OEF) was low in four patients; both had a tendency to decline with advancing age. Although the cause is unknown, it is suggested that impaired oxidative metabolism exists in the Rett syndrome. An analysis of the distribution among brain regions showed that the ratios of values for the frontal cortex to those for the temporal cortex for both the cerebral blood flow (CBF) and CMRO{sub 2} were lower than those for the controls, which may indicate the loss of of hyperfrontality in the Rett syndrome. Distribution of brain metabolism may be immature in the Rett syndrome. (author).

  15. Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms

    DEFF Research Database (Denmark)

    Madsen, J B; Cold, G E; Hansen, E S;

    1987-01-01

    Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classi......Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification......). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping...

  16. Non-invasive optical measurement of cerebral metabolism and hemodynamics in infants.

    Science.gov (United States)

    Lin, Pei-Yi; Roche-Labarbe, Nadege; Dehaes, Mathieu; Carp, Stefan; Fenoglio, Angela; Barbieri, Beniamino; Hagan, Katherine; Grant, P Ellen; Franceschini, Maria Angela

    2013-03-14

    Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO₂). Thus, measures of CMRO₂ are reflective of neuronal viability and provide critical diagnostic information, making CMRO₂ an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO₂) as a surrogate for cerebral oxygen consumption. However, SO₂ is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO₂ are not sensitive enough to detect brain injury hours after the insult, because oxygen consumption and delivery reach equilibrium after acute transients. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO₂ (CMRO₂i). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain

  17. 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

    metabolism in freely moving rats using rapid sampling microdialysis (every minute) coupled to flow-injection analysis (FIA) with biosensors for glucose and lactate. Blood samples for analysis of glucose and lactate were taken at 30-45 min intervals before and after drug dosing and body temperature...... 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...... 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...

  18. 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.

  19. Influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    Hui Lu; Ning-Ning Cui; Bin-Cheng Wang

    2016-01-01

    Objective:To study the influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease. Methods:A total of 58 patients with ischemic cerebrovascular disease in our hospital from April 2015 to January 2016 were selected as the study object, and 58 patients were randomly divided into two groups, 29 patients in control group were treated with routine treatment, 29 patients in observation group were treated with remote ischemic preconditioning on the basic treatment of control group, then the cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment and at first, third and sixth month after the treatment were respectively detected and compared.Results:The cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment all showed no significant differences (allP>0.05), while the cerebral oxygen metabolism and cerebral blood flow indexes of observation group at first, third and sixth month after the treatment were all significantly better than those before the treatment, and the results were all significantly better than those of control group at the same time too (allP>0.05).Conclusions: The influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease are better, and its application value for the patients with ischemic cerebrovascular disease is higher.

  20. Local cerebral metabolism during partial seizures

    Energy Technology Data Exchange (ETDEWEB)

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.; Rausch, R.; Nuwer, M.

    1983-04-01

    Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

  1. DLK1 regulates whole body glucose metabolism

    DEFF Research Database (Denmark)

    Abdallah, Basem; 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 osteoblasts (OBs)-derived undercaboxylated osteocalcin (Glu-OCN) and pancreatic β-cell-insulin; in turn insulin favors osteocalcin bioactivity. These data suggest the existence...... cells acts as a negative feedback mechanism to counteract the stimulatory effects of insulin on osteoblast production of Glu-OCN, a potential mechanism preventing OCN-induced hypoglycemia....

  2. Association of insulin resistance with cerebral glucose uptake in late middle-aged adults at risk for Alzheimer’s disease

    Science.gov (United States)

    Willette, Auriel A.; Bendlin, Barbara B.; Starks, Erika J.; Birdsill, Alex C.; Johnson, Sterling C.; Christian, Bradley T.; Okonkwo, Ozioma C.; La Rue, Asenath; Hermann, Bruce P.; Koscik, Rebecca L.; Jonaitis, Erin M.; Sager, Mark A.; Asthana, Sanjay

    2015-01-01

    related to worse immediate memory (β=0.317, p<.001) and delayed memory (β=0.305, p<.001) performance. Conclusions Our results show that IR, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral IR in order to maintain neural metabolism and cognitive function. PMID:26214150

  3. Glucose Metabolism via the Entner-Doudoroff Pathway in Campylobacter

    DEFF Research Database (Denmark)

    Vegge, Christina S; Jansen van Rensburg, Melissa J; Rasmussen, Janus J;

    2016-01-01

    Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search f...

  4. Decreased cerebral metabolism in stroke-prone spontaneously hypertensive rats (SHRSP) with stroke and its possible improvement by Solcoseryl.

    Science.gov (United States)

    Yamasaki, Y; Yamamoto, Y; Senga, Y; Isogai, M; Shimizu, H; Yamori, Y

    1991-01-01

    Local cerebral glucose utilization (LCGU) was decreased in SHRSP with stroke compared with normotensive Wistar rats. The decrement of LCGU was less in Solcoseryl-treated SHRSP with stroke than that in saline-treated SHRSP with stroke and these brain areas where LCGU was less damaged, in Solcoseryl-treated SHRSP were consistent with the important functioning sites of emotion, motor movement and memory. The result suggests that Solcoseryl may be useful for metabolic improvement of the brain damage after stroke.

  5. The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans

    DEFF Research Database (Denmark)

    Volianitis, S.; Fabricius-Bjerre, A.; Overgaard, A.;

    2008-01-01

    .2% during exercise with an inspired O(2) fraction of 0.17 and 0.30, respectively. Whilst the increase in a-v lactate difference was attenuated by manipulation of cerebral O(2) availability, the cerebral metabolic ratio was not affected significantly. During maximal rowing, the cerebral metabolic ratio...

  6. Propofol Compared to Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Atkinson, D. B.; Ledee, Dolena R.; Kayser, Ernst-Bernhard; Morgan, Phil G.; Sedensky, Margaret M.; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

    2014-01-08

    Anesthetics used in infants and children are implicated in development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in an immature swine model anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon labeled glucose and leucine in the common carotid artery in order to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared-spectroscopy. Compared to isoflurane, propofol depleted ATP and glycogen stores. Propofol also decreased pools of the CAC intermediates, citrate and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked accumulation of lactate. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype which resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations which typically accompany propofol infusion syndrome. These metabolic abnormalities may play a role in neurotoxity observed with propofol in the vulnerable immature brain.

  7. Ventilatory response in metabolic acidosis and cerebral blood volume in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Sluijs, M.C. van der; Oeseburg, B.; Folgering, H.T.M.

    2001-01-01

    The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (5610 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH(4)Cl)

  8. Cerebral blood flow response to functional activation

    DEFF Research Database (Denmark)

    Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill

    2010-01-01

    Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only...

  9. Correlation between cerebral oxygen metabolism and cerebral blood flow simultaneously measured before and after acetazolamide administration

    Science.gov (United States)

    Yamaguchi, Hiroichiro; Yamauchi, Hideto; Hazama, Shiro; Hamamoto, Hirotsugu; Inoue, Nobuhiro

    1999-10-01

    The cerebral circulation and metabolism of ten preoperative cardiac surgery patients were assessed. Alterations in regional cerebral blood flow (rCBF), measured by 123I-N- isopropyl-p-iodo-amphetamine single-photon emission computed tomography, and in cerebral oxygen metabolism, simultaneously detected by near-infrared spectroscopy (NIRS) before and after acetazolamide administration, were investigated. The rCBF (ml/min/100 g) increased significantly from 40.21 +/- 7.65 to 56.24 +/- 13.69 (p equals 0.001), and a significant increase in oxyhemoglobin (Oxy-Hb) of 13.9% (p equals 0.0022) and total hemoglobin (Total-Hb) of 5.7% (0.0047) along with a significant decrease in deoxyhemoglobin (Deoxy-Hb) of 8.9% (p equals 0.0414) were observed concomitantly. Thus, the Oxy-Hb/Total- Hb ratio (%Oxy-Hb) rose significantly from 67.26 +/- 9.82% to 72.98 +/- 8.09% (p equals 0.0022). Examination of the relationships between individual parameters showed that the percentage changes in rCBF and Oxy-Hb were significantly correlated (r equals 0.758, p equals 0.011). The percentage changes in rCBF and %Oxy-Hb were also correlated significantly (r equals 0.740, p equals 0.014). In conclusion, this evidence suggested that NIRS is able to detect relative changes in cerebral hemodynamics and reflect luxury perfusion induced by acetazolamide.

  10. Glucose Metabolism in Sheep Fed Grass Supplemented with Gliricidia Sepium

    Directory of Open Access Journals (Sweden)

    Y. Widiawati

    2014-12-01

    Full Text Available 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 nutritivefeed 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 propionat 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. Fifteen sheeps (18 months old were used in the experiment. Theseare 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]glucoseinfusate was infused continuously through the left jugular venous catheter of each animal to measure glucose metabolism in those sheeps. The 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 theutilization 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with pancreatic and extrapancreatic effects. Studies reveal significant effects in regions of brain tissue that regulate appetite and satiety. The effects cause that mimetics of GLP-1 serves as treatment of type 2 diabete...... and in vivo, as in pancreas. The apparent neuroprotective potential of GLP-1, indirectly acting through changes of cerebral blood flow, glucose metabolism or brain glucose concentration, or all of these, is worthy of close attention....

  12. Implications of Resveratrol on Glucose Uptake and Metabolism

    Directory of Open Access Journals (Sweden)

    David León

    2017-03-01

    Full Text Available Resveratrol—a polyphenol of natural origin—has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for medical applications including cancer and type 2 diabetes. Here, we review the latest advances in understanding how resveratrol modulates glucose uptake, regulates cellular metabolism, and how this may be useful to improve current therapies. We discuss challenges and findings regarding the inhibition of glucose uptake by resveratrol and other polyphenols of similar chemical structure. We review alternatives that can be exploited to improve cancer therapies, including the use of other polyphenols, or the combination of resveratrol with other molecules and their impact on glucose homeostasis in cancer and diabetes.

  13. 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....

  14. Persistence of disturbed thalamic glucose metabolism in a case of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Fellgiebel, Andreas; Scheurich, Armin; Siessmeier, Thomas; Schmidt, Lutz G; Bartenstein, Peter

    2003-10-30

    We report the case of a 40-year-old alcoholic male patient, hospitalized with an acute ataxia of stance and gait, ocular muscle weakness with nystagmus and a global apathetic-confusional state. After admission, an amnestic syndrome with confabulation was also observed and diagnosis of Wernicke-Korsakoff syndrome was made. Under treatment with intravenous thiamine, the patient recovered completely from gaze weakness and ataxia, whereas a severe amnestic syndrome persisted. Fluorodeoxyglucose (FDG) positron emission tomography (PET) showed bilateral thalamic and severe bilateral temporal-parietal hypometabolism resembling a pattern typical for Alzheimer's disease. Longitudinal assessment of the alcohol-abstinent and thiamine-substituted patient revealed improvements of clinical state and neuropsychological performance that were paralleled by recovered cerebral glucose metabolism. In contrast to metabolic rates that increased between 7.1% (anterior cingulate, left) and 23.5% (parietal, left) in cortical areas during a 9-month remission period, thalamic glucose metabolism remained severely disturbed over time (change: left +0.2%, right +0.3%).

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and...... was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism....

  16. 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.

  17. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat

    Energy Technology Data Exchange (ETDEWEB)

    Mraovitch, S.; Calando, Y.; Goadsby, P.J.; Seylaz, J. (Laboratoire de Recherches Cerebrovasculaire, Paris (France))

    1992-06-01

    Changes in cerebral cortical perfusion (CBF{sub LDF}), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with {alpha}-chloralose. CBF{sub LDF} was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic ({sup 14}C)iodoantipyrine and ({sup 14}C)-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. 19 refs., 2 figs., 1 tab.

  18. Blood constituents trigger brain swelling, tissue death, and reduction of glucose metabolism early after acute subdural hematoma in rats.

    Science.gov (United States)

    Baechli, Heidi; Behzad, Melika; Schreckenberger, Matthias; Buchholz, Hans-Georg; Heimann, Axel; Kempski, Oliver; Alessandri, Beat

    2010-03-01

    Outcome from acute subdural hematoma is often worse than would be expected from the pure increase of intracranial volume by bleeding. The aim was to test whether volume-independent pathomechanisms aggravate damage by comparing the effects of blood infusion with those of an inert fluid, paraffin oil, on intracranial pressure (ICP), cerebral perfusion pressure (CPP), local cerebral blood flow (CBF), edema formation, glucose metabolism ([18F]-deoxyglucose, MicroPET ), and histological outcome. Rats were injured by subdural infusion of 300 muL venous blood or paraffin. ICP, CPP, and CBF changes, assessed during the first 30 mins after injury, were not different between the injury groups at most time points (n=8 per group). Already at 2 h after injury, blood caused a significantly more pronounced decrease in glucose metabolism in the injured cortex when compared with paraffin (P<0.001, n=5 per group). Ipsilateral brain edema did not differ between groups at 2 h, but was significantly more pronounced in the blood-treated groups at 24 and 48 h after injury (n=8 per group). These changes caused a 56.2% larger lesion after blood when compared with paraffin (48.1+/-23.0 versus 21.1+/-11.8 mm(3); P<0.02). Blood constituent-triggered pathomechanisms aggravate the immediate effects due to ICP, CPP, and CBF during hemorrhage and lead to early reduction of glucose metabolism followed by more severe edema and histological damage.

  19. 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.

  20. Glucose Metabolism in the Progression of Prostate Cancer

    Science.gov (United States)

    Cutruzzolà, Francesca; Giardina, Giorgio; Marani, Marina; Macone, Alberto; Paiardini, Alessandro; Rinaldo, Serena; Paone, Alessio

    2017-01-01

    Prostate cancer is one of the most common types of cancer in western country males but the mechanisms involved in the transformation processes have not been clearly elucidated. Alteration in cellular metabolism in cancer cells is recognized as a hallmark of malignant transformation, although it is becoming clear that the biological features of metabolic reprogramming not only differ in different cancers, but also among different cells in a type of cancer. Normal prostate epithelial cells have a peculiar and very inefficient energy metabolism as they use glucose to synthesize citrate that is secreted as part of the seminal liquid. During the transformation process, prostate cancer cells modify their energy metabolism from inefficient to highly efficient, often taking advantage of the interaction with other cell types in the tumor microenvironment that are corrupted to produce and secrete metabolic intermediates used by cancer cells in catabolic and anabolic processes. We recapitulate the metabolic transformations occurring in the prostate from the normal cell to the metastasis, highlighting the role of the microenvironment and summarizing what is known on the molecular mechanisms involved in the process. PMID:28270771

  1. Cerebral oxygenation and metabolism during exercise following three months of endurance training in healthy overweight males

    DEFF Research Database (Denmark)

    Seifert, T; Rasmussen, P; Brassard, P

    2009-01-01

    Endurance training improves muscular and cardiovascular fitness, but the effect on cerebral oxygenation and metabolism remains unknown. We hypothesized that 3 mo of endurance training would reduce cerebral carbohydrate uptake with maintained cerebral oxygenation during submaximal exercise. Healthy...... with a lower plasma epinephrine concentration (P exercising at 70% of maximal oxygen uptake (approximately 211 W). Before training, both OCI (3.9 +/- 0.9) and DeltaP(Mito)O(2) (-22 mmHg) decreased (P ... attenuates the cerebral metabolic response to submaximal exercise, as reflected in a lower carbohydrate uptake and maintained cerebral oxygenation....

  2. High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature

    Directory of Open Access Journals (Sweden)

    Wei Li

    2015-08-01

    Full Text Available We previously demonstrated that in normal glucose (5 mM, methylglyoxal (MG, a model of carbonyl stress induced brain microvascular endothelial cell (IHEC dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC. Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia; moreover, barrier function remained disrupted 6 h after cell transfer to normal glucose media (acute glycemic fluctuation. Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG–occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG–occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes.

  3. Prognostic implications of total hemispheric glucose metabolism ratio in cerebro-cerebellar diaschisis

    DEFF Research Database (Denmark)

    Segtnan, Eivind Antonsen; Grupe, Peter; Jarden, Jens Ole

    2017-01-01

    PURPOSE: Diaschisis denotes brain dysfunction remote from a focal brain lesion. We have quantified diaschisis and investigated its prognostic value in glioma. METHODS AND MATERIAL: We compared 50 (18)F-FDG-PET-CT studies collected prospectively from 14 patients with supratentorial glioma (5 men...... and 9 women aged 35-77 years) with 10 single scans from healthy controls aged 43-75 years. Dedicated 3D-segmentation software was used to obtain total hemispheric glucose metabolic ratios (THGr) by dividing total hemispheric (18)F-fluorodeoxyglucose (FDG) uptake in each diaschitic hemisphere, i.......e., the ipsilateral cerebral hemisphere (THGr(Ce)) and the contralateral cerebellar hemisphere (THGr(Cb)), to its respective contralateral side. Receiver operating characteristic (ROC) analysis was performed to determine optimal cut-offs for combinations of THGr(Ce) and THGr(Cb). Two independent observers obtained...

  4. Preoperative cerebral metabolic difference related to the outcome of cochlear implantation in prelingually deaf children

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H.; Lim, G. C.; Ahn, J. H.; Lee, K. S.; Jeong, J. W.; Kim, J. S. [Asan Medical Center, Seoul (Korea, Republic of)

    2007-07-01

    The outcome of cochlear implantation (CI) has known to be variable. The aim of this study was to evaluate the preoperative regional glucose metabolism difference related to the speech perception outcome after CI in prelingually deaf children. Forty-one prelingually deaf children who underwent CI at age 2{approx}10 years were included. All patients underwent F-18 FDG brain PET within one month before CI and measured speech perception using the institute version of the CID at 2 years after CI. Patients were classified into younger (2{approx}6 years) and older (7{approx}10 years) groups. Each group was also divided into a GOOD (CID scores>80) and a BAD (CID scores<60) subgroup. We assessed regional metabolic difference according to CID scores and age by voxel based analysis (SPM2) comparing normal controls (n =8, 20{approx}30 years). Speech perception was good in 19 (68%) of 28 younger patients and 5 (38%) of 13 older patients after CI. Regional metabolism of both younger and older GOOD subgroup was significantly decreased in right temporal, left cerebellar and right frontal regions compared to normal controls (uncorrected p<0.001). In younger GOOD subgroup, left frontotemporal and both parietal regions showed decreased metabolism and right frontal, left temporal and anterior cingulate regions showed increased metabolism compared to BAD subgroup (uncorrected p<0.005). In younger group, regional metabolism in left superior frontal, right temporal and right occipital regions showed a significant negative correlation with CID scores (uncorrected p<0.005). In older group, the pattern of regional metabolic difference correlated with CID score was not similar to that of younger group. Preoperative regional cerebral metabolism is decreased in several brain regions related to the language in preligually deaf patients and the neuralplasty of younger patients are different according to the outcome of speech perception after CI.

  5. 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

  6. 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....

  7. Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis

    DEFF Research Database (Denmark)

    Rom Poulsen, Frantz; Schulz, Mette; Jacobsen, Anne;

    2015-01-01

    BACKGROUND: Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate...... that this technique may separate ischemia and non-ischemic mitochondrial dysfunction. The present study is a retrospective interpretation of biochemical data obtained in a series of patients with severe community-acquired meningitis. METHODS: Cerebral energy metabolism was monitored in 15 patients with severe...... community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio >30 with intracerebral pyruvate level

  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. Insulin signalling and the regulation of glucose and lipid metabolism

    Science.gov (United States)

    Saltiel, Alan R.; Kahn, C. Ronald

    2001-12-01

    The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.

  10. Enhanced muscle glucose metabolism after exercise in the rat

    DEFF Research Database (Denmark)

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

    1984-01-01

    glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity...... to near base-line values and only the increase in insulin sensitivity persists. It is proposed that phase I corresponds to the period of rapid glycogen repletion that immediately follows exercise and phase II to the period of supercompensation....

  11. Berberine improves glucose metabolism through induction of glycolysis.

    Science.gov (United States)

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

    2008-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. 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 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for > or =16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio.

  12. 一氧化碳中毒迟发脑病患者高压氧综合治疗前后脑葡萄糖代谢的变化%Change of cerebral metabolism rate of glucose in patient of delayed neuropsychologlcal sequelae after CO poisoning following combining hyperbaric oxygen treatment

    Institute of Scientific and Technical Information of China (English)

    高宇; 高春锦; 王铁; 葛环; 武连华; 赵立明; 宋振国

    2008-01-01

    Objective To estimate the effect of hyperbaric oxygen treatment on cerebral metabolism rate of glucose(CMRglc)in patients with delayed neuropsychological sequelae after CO poisoning(DNS).Methods Thirty cases of DNS were received 18F-FDGPET examination before hyperbaric oxygen treatment (HBOT)and after 40th HBOT respectively.At the same time 17 healthy examiner were also received 18F-FDG PET examination.Radioactive counts in bilateral frontal lobe,parietal lobe,temporal lobe,occipital lobe and ipsilateral cerebellum unit area were recorded,and the radio of radioactive counts were measured and used to evaluate PET study as semi-quantitative parameter.Results The CMRglc of DNS patient decreased in bilateral frontal lobe,parietal lobe,temporal lobe and occipital lobe before HBOT(P<0.05).After HBOT,there were obvious improvement of CMRglc in bilateral parietal lobe,occipital lobe and left side temporal lobe(P<0.05)and no differences in bilateral frontal lobe and right side temporal lobe.Conclusions The CMRglc decreased on the early phase of DNS.Combining hyperbaric oxygen treatment can improve CMRglc and cerebral function.%目的 观察一氧化碳中毒迟发脑病高压氧综合治疗前后患者脑葡萄糖代谢的变化,探讨高压氧综合治疗的作用.方法 一氧化碳中毒迟发脑病(DNS)患者30例(DNS组),高压氧综合治疗前及治疗40次后分别接受18F标记的脱氧葡萄糖正电子发射断层扫描(18F-FDG PET)检查,同时对17例年龄匹配的健康体检者(对照组)进行18F-FDG PET检查.记录DNS组与对照组的双侧额叶、顶叶、颞叶、枕叶与同侧小脑单位面积的放射性计数;计算双侧额叶、顶叶、颞叶、枕叶与同侧小脑单位面积放射性计数的比值,以此比值作为PET研究的半定量观察指标.结果 DNS组高压氧综合治疗前双侧的额/小脑、顶/小脑、颞/小脑、枕/1h脑的比值明显低于对照组(P<0.05);高压氧综合治疗40次后,双侧的顶/小脑、

  13. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling.

  14. Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized (13)C Magnetic Resonance Spectroscopic Imaging

    DEFF Research Database (Denmark)

    Butt, Sadia Asghar; Søgaard, Lise Vejby-Christensen; Magnusson, Peter O.;

    2012-01-01

    The branched chain amino acid transaminase (BCAT) has an important role in nitrogen shuttling and glutamate metabolism in the brain. The purpose of this study was to describe the cerebral distribution and metabolism of hyperpolarized 2-keto[1-(13)C]isocaproate (KIC) in the normal rat using magnetic...... resonance modalities. Hyperpolarized KIC is metabolized to [1-(13)C]leucine (leucine) by BCAT. The results show that KIC and its metabolic product, leucine, are present at imageable quantities 20 seconds after end of KIC administration throughout the brain. Further, significantly higher metabolism...... was observed in hippocampal regions compared with the muscle tissue. In conclusion, the cerebral metabolism of hyperpolarized KIC is imaged and hyperpolarized KIC may be a promising substrate for evaluation of cerebral BCAT activity in conjunction with neurodegenerative disease.Journal of Cerebral Blood Flow...

  15. Cerebral hemodynamics and metabolism in patients with moyamoya disease not demonstrating either cerebral infarct or hemorrhage on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kuwabara, Yasuo; Ichiya, Yuichi; Sasaki, Masayuki; Akashi, Yuko; Yoshida, Tsuyoshi; Fukumura, Toshimitsu; Masuda, Kouji; Matsushima, Toshio; Fukui, Masashi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1995-12-01

    We evaluated the cerebral hemodynamics and metabolism in moyamoya patients who did not demonstrate either cerebral infarct or hemorrhage on MRI. The subjects consisted of 5 patients with moyamoya disease (4 females and one male, aged from 15 to 40 ears). The CBF, OEF and CMRO{sub 2} of the moyamoya patients did not differ from those of the normal control subjects. The CBV did increase significantly in the cerebral cortices and striatum, but not in the cerebellum. The TT was also significantly prolonged in the frontal and parietal regions. The cerebrovascular CO{sub 2} response was markedly impaired in the frontal, temporal and parietal cortices. However, it was relatively preserved in the occipital cortex, thalamus and cerebellum. Thus, the cerebral hemodynamic reserve capacity decreased even in the moyamoya patients not demonstrating either cerebral infarct or hemorrhage on MRI, and it should be considered in the management of these patients. (author).

  16. Lactate storm marks cerebral metabolism following brain trauma.

    Science.gov (United States)

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

    2014-07-18

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

  17. Fatigue in Parkinson's disease: The contribution of cerebral metabolic changes.

    Science.gov (United States)

    Cho, Sang Soo; Aminian, Kelly; Li, Crystal; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2017-01-01

    Fatigue is a common and disabling non-motor symptom in Parkinson's disease associated with a feeling of overwhelming lack of energy. The aim of this study was to identify the neural substrates that may contribute to the development of fatigue in Parkinson's disease. Twenty-three Parkinson's disease patients meeting UK Brain Bank criteria for the diagnosis of idiopathic Parkinson's disease were recruited and completed the 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG)-PET scan. The metabolic activities of Parkinson's disease patients with fatigue were compared to those without fatigue using statistical parametric mapping analysis. The Parkinson's disease group exhibiting higher level of fatigue showed anti-correlated metabolic changes in cortical regions associated with the salience (i.e., right insular region) and default (i.e., bilateral posterior cingulate cortex) networks. The metabolic abnormalities detected in these brain regions displayed a significant correlation with level of fatigue and were associated with a disruption of the functional correlations with different cortical areas. These observations suggest that fatigue in Parkinson's disease may be the expression of metabolic abnormalities and impaired functional interactions between brain regions linked to the salience network and other neural networks. Hum Brain Mapp 38:283-292, 2017. © 2016 Wiley Periodicals, Inc.

  18. Sympathetic influence on cerebral blood flow and metabolism during exercise in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Secher, Niels H

    2011-01-01

    This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF......, but increases during cycling exercise. The increase in CMRO(2) is unaffected by beta-adrenergic blockade even though CBF is reduced suggesting that cerebral oxygenation becomes critical and a limited cerebral mitochondrial oxygen tension may induce fatigue. Also, sympathetic activity may drive cerebral non...

  19. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling

    Energy Technology Data Exchange (ETDEWEB)

    Hassel, B.

    1995-11-01

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.

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

    Science.gov (United States)

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

    2016-06-01

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

  1. Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes

    Science.gov (United States)

    Bally, Lia; Kempf, Patrick; Zueger, Thomas; Speck, Christian; Pasi, Nicola; Ciller, Carlos; Feller, Katrin; Loher, Hannah; Rosset, Robin; Wilhelm, Matthias; Boesch, Chris; Buehler, Tania; Dokumaci, Ayse S.; Tappy, Luc; Stettler, Christoph

    2017-01-01

    This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU) with glucose alone (GLU) in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol)) underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU) or glucose alone (GLU) to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46). Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg−1·min−1, p 0.05 for all). Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen. PMID:28230765

  2. Ghrelin function in insulin release and glucose metabolism.

    Science.gov (United States)

    Dezaki, Katsuya

    2013-01-01

    Given its wide spectrum of biological activities such as growth hormone (GH) release, feeding stimulation, adiposity and cardiovascular actions, the discovery of ghrelin opened many new perspectives within neuroendocrine, metabolic and cardiovascular research, thus suggesting its possible clinical application. Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues. Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats and humans. The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release. Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro. Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models. Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand. Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.

  3. Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study

    Science.gov (United States)

    Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M.; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

    2008-01-01

    Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention. PMID:18322043

  4. PET imaging of cerebral perfusion and oxygen metabolism in stroke

    Energy Technology Data Exchange (ETDEWEB)

    Pointon, O.; Yasaka, M.; Berlangieri, S.U.; Newton, M.R.; Thomas, D.L.; Chan, C.G.; Egan, G.F.; Tochon-Danguy, H.J.; O``Keefe, G.; Donnan, G.A.; McKay, W.J. [Austin Hospital, Melbourne, VIC (Australia). Centre for PET and Depts of Nuclear Medicine and Neurology

    1998-03-01

    Full text: Stroke remains a devastating clinical event with few therapeutic options. In patients with acute stroke, we studied the cerebral perfusion and metabolic patterns with {sup 15}O-CO{sub 2} or H{sub 2}O and {sup 15}O-O{sub 2} positron emission tomography and correlated these findings to the clinical background. Forty three patients underwent 45 studies 0-23 days post-stroke (mean 7 days). Fifteen patients showed luxury perfusion (Group A), 10 had matched low perfusion and metabolism (B) and 3 showed mixed pattern including an area of misery perfusion (C). Seventeen showed no relevant abnormality (D) and there were no examples of isolated misery perfusion. Twelve of the 15 in Group A had either haemorrhagic transformation on CT, re-opening on angiography, or a cardioembolic mechanism. In contrast only 5/10 in Group B, 0/3 in Group C and 2/17 in Group D had these features. Although 7/10 in group B had moderate or large size infarcts on CT the incidence of haemorrhagic transformation was low (2/10) and significant carotid stenoses were more common in those studied (5/8) compared with the other groups. Misery perfusion was not seen beyond five days. Thus, luxury perfusion seems to be related to a cardio-embolic mechanism or reperfusion. Matched low perfusion and metabolism was associated with a low rate of haemorrhagic transformation despite a high incidence of moderate to large size infarcts. Misery perfusion is an early phenomenon in the evolution of ischaemic stroke.

  5. Symptoms of depression in people with impaired glucose metabolism or Type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Adriaanse, M C; Dekker, J M; Heine, R. J.

    2008-01-01

    OBJECTIVE: To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2). RESEARCH DESIGN AND METHODS: Cross-sectional data from a population-based cohort study conducted...... among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D score > or = 16). Glucose metabolism status was determined by means of fasting and post-load glucose levels...

  6. 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.

  7. Effect of oxandrolone on glucose metabolism in growth hormone-treated girls with Turner syndrome

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Stijnen, T.; Zandwijken, G.R.; Muinck Keizer-Schrama, S.M.P.F. de; Otten, B.J.; Wit, J.M.

    2011-01-01

    BACKGROUND: The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). METHODS: In a randomized, placebo-controlled, double-blind study, we assessed the effect of Ox at a dosage of either 0.06 or 0.03 mg/kg/day on glucose metabol

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

    Science.gov (United States)

    Pichette, Jennifer; Gagnon, Jeffrey

    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.

  9. Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat

    DEFF Research Database (Denmark)

    Linde, Rasmus; Hasselbalch, Steen G.; Topp, Simon;

    2006-01-01

    In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated...

  10. 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

  11. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Knudsen, Karen Birgitte Moos; Kondrup, Jens;

    2001-01-01

    BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine...... metabolism. METHODS: The study consisted of patients with FHF (n = 16) or cirrhosis (n = 5), and healthy subjects (n = 8). Cerebral blood flow was measured by the 133Xe washout technique. Blood samples for determination of ammonia and amino acids were drawn simultaneously from the radial artery...... and the internal jugular bulb. RESULTS: A net cerebral ammonia uptake was only found in patients with FHF (1.62 +/- 0.79 micromol x 100 g(-1) x min(-1)). The cerebral glutamine efflux was higher in patients with FHF than in the healthy subjects and cirrhotics, -6.11 +/- 5.19 vs. -1.93 +/- 1.17 and -1.50 +/- 0...

  12. Metabolism of [U-13C]glucose in Human Brain Tumors In Vivo

    Science.gov (United States)

    Maher, Elizabeth A.; Marin-Valencia, Isaac; Bachoo, Robert M.; Mashimo, Tomoyuki; Raisanen, Jack; Hatanpaa, Kimmo J.; Jindal, Ashish; Jeffrey, F. Mark; Choi, Changho; Madden, Christopher; Mathews, Dana; Pascual, Juan M.; Mickey, Bruce E.; Malloy, Craig R.; DeBerardinis, Ralph J.

    2012-01-01

    Glioblastomas (GBMs) and brain metastases demonstrate avid uptake of 18fluoro-2-deoxyglucose (FDG) by positron emission tomography (PET) and display perturbations of intracellular metabolite pools by 1H magnetic resonance spectroscopy (MRS). These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. FDG-positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation compared to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain malignancies to oxidize glucose in the tricarboxylic acid cycle is unknown. Here we studied the metabolism of human brain tumors in situ. [U-13C]glucose was infused during surgical resection, and tumor samples were subsequently subjected to 13C NMR spectroscopy. Analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the TCA cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl-CoA pool was derived from blood-borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of 13C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse malignancies growing in their native microenvironment. PMID:22419606

  13. Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of acetate and glucose metabolism in the rat.

    Science.gov (United States)

    Serres, Sébastien; Bezancon, Eric; Franconi, Jean-Michel; Merle, Michel

    2007-06-01

    The occurrence of pyruvate recycling in the rat brain was studied in either pentobarbital anesthetized animals or awake animals receiving a light analgesic dose of morphine, which were infused with either [1-13C]glucose + acetate or glucose + [2-13C]acetate for various periods of time. Metabolite enrichments in the brain, blood and the liver were determined from NMR analyses of tissue extracts. They indicated that: (i) Pyruvate recycling was revealed in the brain of both the anesthetized and awake animals, as well as from lactate and alanine enrichments as from glutamate isotopomer composition, but only after infusion of glucose + [2-13C]acetate. (ii) Brain glucose was labelled from [2-13C]acetate at the same level in anaesthetized and awake rats (approximately 4%). Comparing its enrichment with that of blood and liver glucose indicated that brain glucose labelling resulted from hepatic gluconeogenesis. (iii) Analysing glucose 13C-13C coupling in the brain, blood and the liver confirmed that brain glucose could be labelled in the liver through the activities of both pyruvate recycling and gluconeogenesis. (iv) The rate of appearance and the amount of brain glutamate C4-C5 coupling, a marker of pyruvate recycling when starting from [2-13C]acetate, were lower than those of brain glucose labelling from hepatic metabolism. (v) The evaluation of the contributions of glucose and acetate to glutamate metabolism revealed that more than 60% of brain glutamate was synthesized from glucose whereas only 7% was from acetate and that glutamate C4-C5 coupling was mainly due to the metabolism of glucose labelled through hepatic gluconeogenesis. All these results indicate that, under the present conditions, the pyruvate recycling observed through the labelling of brain metabolites mainly originates from peripheral metabolism.

  14. Differential Incorporation of Glucose into Biomass during Warburg Metabolism

    OpenAIRE

    Chen, Ying-Jr; Huang, Xiaojing; Mahieu, Nathaniel G.; Cho, Kevin; Schaefer, Jacob; Patti, Gary J.

    2014-01-01

    It is well established that most cancer cells take up an increased amount of glucose relative to that taken up by normal differentiated cells. The majority of this glucose carbon is secreted from the cell as lactate. The fate of the remaining glucose carbon, however, has not been well-characterized. Here we apply a novel combination of metabolomic technologies to track uniformly labeled glucose in HeLa cancer cells. We provide a list of specific intracellular metabolites that become enriched ...

  15. 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.

  16. Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Lia Bally

    2017-02-01

    Full Text Available This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU with glucose alone (GLU in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU or glucose alone (GLU to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46. Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg−1·min−1, p < 0.001 and carbohydrate oxidation lower (18.1 ± 0.8 vs. 24.5 ± 0.8 mg·kg−1·min−1 p < 0.001 in GLUFRU compared to GLU, with decreased muscle glycogen oxidation in GLUFRU (10.2 ± 0.9 vs. 17.5 ± 1.0 mg·kg−1·min−1, p < 0.001. Lactate levels were higher (2.2 ± 0.2 vs. 1.8 ± 0.1 mmol/L, p = 0.012 in GLUFRU, with comparable counter-regulatory hormones between GLUFRU and GLU (p > 0.05 for all. Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen.

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

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

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

  18. High-Density Lipoprotein Modulates Glucose Metabolism in Patients With Type 2 Diabetes Mellitus

    NARCIS (Netherlands)

    Drew, Brian G.; Duffy, Stephen J.; Formosa, Melissa F.; Natoli, Alaina K.; Henstridge, Darren C.; Penfold, Sally A.; Thomas, Walter G.; Mukhamedova, Nigora; de Courten, Barbora; Forbes, Josephine M.; Yap, Felicia Y.; Kaye, David M.; van Hall, Gerrit; Febbraio, Mark A.; Kemp, Bruce E.; Sviridov, Dmitri; Steinberg, Gregory R.; Kingwell, Bronwyn A.

    2009-01-01

    Background-Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP-activat

  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. Glucose metabolism in isolated rat adipocytes: estimate of total recovery by the product summation method.

    Science.gov (United States)

    Groff, J L; Stugard, C E; Mays, C J; Koopmans, H S; DiGirolamo, M

    1992-03-01

    To determine the completeness of glucose recovery into its metabolic products, adipocyte glucose utilization was compared by two different methods in a basal and in an insulin-stimulated metabolic state. One of the methods (product summation) is based on the recovery of (( U-14C ))-labeled glucose in carbon dioxide and triglyceride, together with the assay of lactate and pyruvate released into the medium from the incubated cells. The second method is a modification of a procedure by which the quantity of tritiated water that is released by metabolism from +AD5-3H+BD-labeled glucose is determined. It was found that the results of the two methods were in very close agreement. Neither method measures glucose conversion to glycogen. However, glycogenic activity is very low in adipocytes and represents only a small percentage of utilized glucose. Therefore, the finding of comparable results between the two methods suggests that the summation of the metabolic products carbon dioxide, triglyceride, lactate, and pyruvate does account for nearly all of the glucose utilized. This has important implications for the understanding of the considerable variations in rate and patterns of glucose metabolism by the fat cells under a variety of experimental conditions.

  1. Cerebral blood flow and metabolism in adults with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten

    2007-01-01

    The intense intrathecal inflammation observed in acute bacterial meningitis (ABM) is associated with pronounced changes in cerebral blood flow (CBF) and metabolism. In seven substudies, CBF and metabolism were measured in adults with ABM as well as healthy volunteers during various interventions...

  2. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Deshmukh, Atul; Long, Yun Chau

    2007-01-01

    suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were...... incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P ... exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure....

  3. The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Ewa Jablonska

    2016-12-01

    Full Text Available The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast. Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

  4. The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

    Science.gov (United States)

    Jablonska, Ewa; Reszka, Edyta; Gromadzinska, Jolanta; Wieczorek, Edyta; Krol, Magdalena B.; Raimondi, Sara; Socha, Katarzyna; Borawska, Maria H.; Wasowicz, Wojciech

    2016-01-01

    The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects. PMID:27983572

  5. Cerebral carbohydrate cost of physical exertion in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ogoh, Shigehiko; Dawson, Ellen A

    2004-01-01

    Above a certain level of cerebral activation the brain increases its uptake of glucose more than that of O(2), i.e., the cerebral metabolic ratio of O(2)/(glucose + 12 lactate) decreases. This study quantified such surplus brain uptake of carbohydrate relative to O(2) in eight healthy males who p...

  6. 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...... was seen in the dizygotic twins. The effect of the polymorphisms on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism or through free fatty acids exerting their effect on glucose metabolism.......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...

  7. Alleviation of glucose repression of maltose metabolism by MIG1 disruption in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

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

    1996-01-01

    The MIG1 gene was disrupted in a haploid laboratory strain (B224) and in an industrial polyploid strain (DGI 342) of Saccharomyces cerevisiae. The alleviation of glucose repression of the expression of MAL genes and alleviation of glucose control of maltose metabolism were investigated in batch...... cultivations on glucose-maltose mixtures. In the MIG1-disrupted haploid strain, glucose repression was partly alleviated; i.e., maltose metabolism was initiated at higher glucose concentrations than in the corresponding wild-type strain. In contrast, the polyploid Delta mig1 strain exhibited an even more...... of glucose repression of the SUC genes. The disruption of MIG1 was shown to bring about pleiotropic effects, manifested in changes in the pattern of secreted metabolites and in the specific growth rate....

  8. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  9. Impaired fasting blood glucose is associated to cognitive impairment and cerebral atrophy in middle-aged non-human primates

    Science.gov (United States)

    Djelti, Fathia; Dhenain, Marc; Terrien, Jérémy; Picq, Jean-Luc; Hardy, Isabelle; Champeval, Delphine; Perret, Martine; Schenker, Esther; Epelbaum, Jacques; Aujard, Fabienne

    2017-01-01

    Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper normal range are associated with memory impairment and cerebral atrophy. Due to a close evolutional similarity to Man, non-human primates may be useful to investigate the relationships between glucose homeostasis, cognitive deficits and structural brain alterations. In the grey mouse lemur, Microcebus murinus, spatial memory deficits have been associated with age and cerebral atrophy but the origin of these alterations have not been clearly identified. Herein, we showed that, on 28 female grey mouse lemurs (age range 2.4-6.1 years-old), age correlated with impaired fasting blood glucose (rs=0.37) but not with impaired glucose tolerance or insulin resistance. In middle-aged animals (4.1-6.1 years-old), fasting blood glucose was inversely and closely linked with spatial memory performance (rs=0.56) and hippocampus (rs=−0.62) or septum (rs=−0.55) volumes. These findings corroborate observations in humans and further support the grey mouse lemur as a natural model to unravel mechanisms which link impaired glucose homeostasis, brain atrophy and cognitive processes. PMID:28039490

  10. 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

  11. 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.

  12. Metabolic Fate of Fructose Ingested with and without Glucose in a Mixed Meal

    OpenAIRE

    Fanny Theytaz; Sara de Giorgi; Leanne Hodson; Nathalie Stefanoni; Valentine Rey; Philippe Schneiter; Vittorio Giusti; Luc Tappy

    2014-01-01

    Ingestion of pure fructose stimulates de novo lipogenesis and gluconeogenesis. This may however not be relevant to typical nutritional situations, where fructose is invariably ingested with glucose. We therefore assessed the metabolic fate of fructose incorporated in a mixed meal without or with glucose in eight healthy volunteers. Each participant was studied over six hours after the ingestion of liquid meals containing either 13C-labelled fructose, unlabeled glucose, lipids and protein (Fr...

  13. Complex Patterns of Metabolic and Ca2+ Entrainment in Pancreatic Islets by Oscillatory Glucose

    OpenAIRE

    Pedersen, Morten Gram; Mosekilde, Erik; Polonsky, Kenneth S.; Luciani, Dan S.

    2013-01-01

    Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca2+ in pancreatic islets. Periodic variations in glucose can entrain islet Ca2+ and insulin secretion, possibly promoting interislet synchronization. Here, we used fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) i...

  14. Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

    Directory of Open Access Journals (Sweden)

    Lars Stechemesser

    2017-01-01

    Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

  15. Impact of 3-year lifestyle intervention on postprandial glucose metabolism : the SLIM study

    NARCIS (Netherlands)

    Roumen, C.; Corpeleijn, E.; Feskens, E. J. M.; Mensink, M.; Saris, W. H. M.; Blaak, E. E.

    2008-01-01

    Objective To determine the effect of a 3-year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT). Methods The study was a

  16. Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

    DEFF Research Database (Denmark)

    Lidegaard, Lærke P; Hansen, Anne-Louise Smidt; Johansen, Nanna B

    2015-01-01

    AIM/HYPOTHESIS: Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test...

  17. Sympathetic influence on cerebral blood flow and metabolism during exercise in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Secher, Niels H

    2011-01-01

    , but not by beta1-adrenergic blockade. Furthermore, endurance training appears to lower the cerebral non-oxidative carbohydrate uptake and preserve cerebral oxygenation during submaximal exercise. This is possibly related to an attenuated catecholamine response. Finally, exercise promotes brain health as evidenced......This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF...... as evidenced by pharmacological manipulation of adrenergic and cholinergic receptors. Cholinergic blockade by glycopyrrolate blocks the exercise-induced increase in the transcranial Doppler determined mean flow velocity (MCA Vmean). Conversely, alpha-adrenergic activation increases that expression of cerebral...

  18. Regulation of glucose and glycogen metabolism during and after exercise

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Richter, Erik

    2012-01-01

    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport...... in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation)....

  19. Metabolic ketoacidosis with normal blood glucose: A rare complication of sodium–glucose cotransporter 2 inhibitors

    OpenAIRE

    Saad Ullah; Noman Khan; Hassan Zeb; Hassan Tahir

    2016-01-01

    Ketoacidosis is a significant and often a life-threatening complication of diabetes mellitus seen mostly in type 1 diabetes mellitus as well as occasionally in type 2 diabetes mellitus. Diabetic ketoacidosis usually manifests with high blood glucose more than 250 mg/dL, but euglycemic diabetic ketoacidosis is defined as ketoacidosis associated with blood glucose level less than 250 mg/dL. Normal blood glucose in such patients results in significant delay in diagnosis and management of diabeti...

  20. 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...... in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell. Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was unaltered......; however its ability to stimulate the incorporation of [(14)C]glucose into glycogen in certain muscles was enhanced. Thus at a concentration of 75 muU/ml insulin stimulated glycogen synthesis eightfold more in the fast-twitch red fibers of the red gastrocnemius than it did in the same muscle...

  1. Time-dependent changes in cerebral blood flow after acetazolamide loading into patients with hemodynamic cerebral ischemia. Relationship to cerebral oxygen metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masakazu [Iwate Medical Univ., Morioka (Japan). School of Medicine

    2001-10-01

    The aim of this study was to clarify the relationship between time-dependent changes in cerebral blood flow (CBF) after acetazolamide loading and cerebral oxygen metabolism (CMRO{sub 2}). The subjects consisted of 30 patients with severe stenosis or occlusion of either internal carotid, middle cerebral, or vertebro-basilar artery. Regional CBF was measured at the resting state and 6, 16 and 30 minutes after intravenous administration of 1 gram of acetazolamide using the positron emission tomography in combination with the [{sup 15}O] H{sub 2}O bolus-injection method. Prior to CBF study, regional cerebral oxygen extraction fraction (OEF) was measured using the [{sup 15}O] O{sub 2} inhalation method. Regional CMRO{sub 2} was calculated based on CBF and OEF. According to the time-dependent changes in CBF responses to acetazolamide loading, the CBF responses are classified into good response type, paradoxical response type, and poor response type. Good response type (CBF increase rate more than 20% 6 minutes after acetazolamide loading), paradoxical response type (decrease of CBF 6 minutes after acetazolamide loading) and poor response type (CBF increase rate less than 20% 6 minutes after acetazolamide loading) were identified in 39, 11 and 10 areas, respectively. Brain areas with good response type showed normal OEF and normal CMRO{sub 2}. Brain areas with paradoxical response type showed increased OEF and normal CMRO{sub 2}. Brain areas with poor response type showed normal OEF and decreased CMRO{sub 2}. In view of these findings, the writer concludes that sequential measurement of cerebral blood flow (CBF) after acetazolamide loading enables one to know the regional cerebral oxygen metabolic state in patients with hemodynamic ischemia, and CBF should be measured at an early stage after the administration of acetazolamide to accurately detect misery perfusion. (author)

  2. Androgenic/estrogenic balance in the male rat cerebral circulation: metabolic enzymes and sex steroid receptors.

    Science.gov (United States)

    Gonzales, Rayna J; Ansar, Saema; Duckles, Sue P; Krause, Diana N

    2007-11-01

    Tissues from males can be regulated by a balance of androgenic and estrogenic effects because of local metabolism of testosterone and expression of relevant steroid hormone receptors. As a critical first step to understanding sex hormone influences in the cerebral circulation of males, we investigated the presence of enzymes that metabolize testosterone to active products and their respective receptors. We found that cerebral blood vessels from male rats express 5alpha-reductase type 2 and aromatase, enzymes responsible for conversion of testosterone into dihydrotestosterone (DHT) and 17beta-estradiol, respectively. Protein levels of these enzymes, however, were not modulated by long-term in vivo hormone treatment. We also showed the presence of receptors for both androgens (AR) and estrogens (ER) from male cerebral vessels. Western blot analysis showed bands corresponding to the full-length AR (110 kDa) and ERalpha (66 kDa). Long-term in vivo treatment of orchiectomized rats with testosterone or DHT, but not estrogen, increased AR levels in cerebral vessels. In contrast, ERalpha protein levels were increased after in vivo treatment with estrogen but not testosterone. Fluorescent immunostaining revealed ERalpha, AR, and 5alpha-reductase type 2 in both the endothelial and smooth muscle layers of cerebral arteries, whereas aromatase staining was solely localized to the endothelium. Thus, cerebral vessels from males are target tissues for both androgens and estrogen. Furthermore, local metabolism of testosterone might balance opposing androgenic and estrogenic influences on cerebrovascular as well as brain function in males.

  3. Cerebral blood flow and metabolism for Broca's aphasia using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Toshiaki

    1987-12-01

    A total of 11 patients with Broca's aphasia (BA) underwent positron emission tomography (PET) with the purpose of investigating the responsible region and the symptomatic flow and metabolism thresholds for BA. Computed tomography (CT) was concurrently performed. In the group of 3 patients undergoing PET with C-11 glucose, both PET and CT provided abnormal findings in the region that is thought to be responsible for BA (Broca's area), including the cortex and subcortex in the anterior region to Sylvian fissure. The Broca's area in the remaining one was shown as low C-11 accumulation area on PET and as isodensity on CT. The second group, consisting of 8 BA patients and 30 control patients without BA, underwent PET using O-15 steady method. PET showed reduction of regional cerebral blood flow (rCBF) and oxygen metabolic rate (rCMRO/sub 2/) in the Broca's area in all BA patients. Computed tomography showed abnormal low density in the Broca's area in 3 patients, and abnormal findings in the basal ganglionic region and subcortex without evidence for abnormal low density in the Broca's area in the other 5 patients. Comparison of rCBF and rCMRO/sub 2/ in BA patients with those in control patients may show the symptomatic thresholds to be 20 - 27 ml100 gmin for rCBF and 2.0 ml100 gmin for rCMRO/sub 2/. (Namekawa, K.).

  4. Pregnancy and undernutrition alter glucose metabolic responses to insulin in sheep.

    Science.gov (United States)

    Petterson, J A; Dunshea, F R; Ehrhardt, R A; Bell, A W

    1993-07-01

    Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Whole-body kinetics of glucose metabolism were measured under basal conditions, and the hyperinsulinemic, euglycemic clamp technique was used to define insulin-dose response profiles for several indices of whole-body glucose utilization, and for endogenous glucose production. Pregnancy increased and undernutrition decreased basal glucose entry rate (GER), glucose metabolic clearance rate (GMCR) and insulin-independent glucose utilization (IIGU). The consistent increment in IIGU of pregnant over nonpregnant ewes was comparable to previous estimates of uterine glucose uptake. Pregnancy resulted in higher plasma concentration for 50% maximal responses (ED50) to insulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to maintain euglycemia and insulin-dependent glucose utilization (IDGU). These changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (Rmax) were relatively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insulin-induced suppression of endogenous glucose production was significantly lower due to undernutrition; neither Rmax nor ED50 for this response was affected by pregnancy. Insulin resistance in late-pregnant ewes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.

  5. 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.

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

    DEFF Research Database (Denmark)

    Hao, Qin; Yadav, Rachita; Basse, Astrid L.

    2015-01-01

    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...... 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...

  7. The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics

    DEFF Research Database (Denmark)

    Karstoft, Kristian; Mortensen, Stefan; Knudsen, Sine H;

    2015-01-01

    The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under eu- and hyperglycemic conditions. Young, healthy males (n=10) underwent three trials in a randomized, controlled, cross-over study. Each trial...... consisted of a 2-stage (eu- and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism were measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial and common carotid artery blood flow...... a higher femoral blood flow during hyperglycemia in GIP (vs. CON and GLP-1, Pmetabolism or hemodynamics during euglycemia. On contrary, during...

  8. 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.

  9. Comparison of glucose and lipid metabolic gene expressions between fat and lean lines of rainbow trout after a glucose load.

    Directory of Open Access Journals (Sweden)

    Junyan Jin

    Full Text Available Two experimental rainbow trout lines developed through divergent selection for low (Lean 'L' line or high (Fat 'F' line muscle fat content were used as models to study the genetic determinism of fat depots. Previous nutritional studies suggested that the F line had a better capability to use glucose than the L line during feeding trials. Based on that, we put forward the hypothesis that F line has a greater metabolic ability to clear a glucose load effectively, compared to L line. In order to test this hypothesis, 250 mg/kg glucose was intraperitoneally injected to the two rainbow trout lines fasted for 48 h. Hyperglycemia was observed after glucose treatment in both lines without affecting the phosphorylation of AMPK (cellular energy sensor and Akt-TOR (insulin signaling components. Liver glucokinase and glucose-6-phosphate dehydrogenase expression levels were increased by glucose, whereas mRNA levels of β-oxidation enzymes (CPT1a, CPT1b, HOAD and ACO were down-regulated in the white skeletal muscle of both lines. Regarding the genotype effect, concordant with normoglycemia at 12 h after glucose treatment, higher muscle glycogen was found in F line compared to L line which exhibited hyperglycemia. Moreover, mRNA levels of hepatic glycolytic enzymes (GK, 6PFK and PK, gluconeogenic enzyme PEPCK and muscle fatty acid oxidation enzymes (CPT1a, CPT1b and HOAD were concurrently higher in the F line. Overall, these findings suggest that F line may have a better ability to maintain glucose homeostasis than L line.

  10. Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

    DEFF Research Database (Denmark)

    Dam, Gitte; Keiding, Susanne; Munk, Ole L

    2013-01-01

    Studies have shown decreased cerebral oxygen metabolism (CMRO(2)) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood...... ammonia concentration and cerebral metabolic rate of blood ammonia (CMRA). We addressed these questions in a paired study design by investigating patients with cirrhosis during and after recovery from an acute episode of HE type C. CMRO(2), CBF, and CMRA were measured by dynamic positron emission...

  11. Metabolic ketoacidosis with normal blood glucose: A rare complication of sodium–glucose cotransporter 2 inhibitors

    Science.gov (United States)

    Ullah, Saad; Khan, Noman; Zeb, Hassan; Tahir, Hassan

    2016-01-01

    Ketoacidosis is a significant and often a life-threatening complication of diabetes mellitus seen mostly in type 1 diabetes mellitus as well as occasionally in type 2 diabetes mellitus. Diabetic ketoacidosis usually manifests with high blood glucose more than 250 mg/dL, but euglycemic diabetic ketoacidosis is defined as ketoacidosis associated with blood glucose level less than 250 mg/dL. Normal blood glucose in such patients results in significant delay in diagnosis and management of diabetic ketoacidosis, thus increasing mortality and morbidity. We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient. PMID:27928503

  12. Metabolic ketoacidosis with normal blood glucose: A rare complication of sodium–glucose cotransporter 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Saad Ullah

    2016-11-01

    Full Text Available Ketoacidosis is a significant and often a life-threatening complication of diabetes mellitus seen mostly in type 1 diabetes mellitus as well as occasionally in type 2 diabetes mellitus. Diabetic ketoacidosis usually manifests with high blood glucose more than 250 mg/dL, but euglycemic diabetic ketoacidosis is defined as ketoacidosis associated with blood glucose level less than 250 mg/dL. Normal blood glucose in such patients results in significant delay in diagnosis and management of diabetic ketoacidosis, thus increasing mortality and morbidity. We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.

  13. Effects of an oral insulin nanoparticle administration on hepatic glucose metabolism assessed by 13C and 2H isotopomer analysis

    NARCIS (Netherlands)

    Reis, C.P.; Neufeld, R.; Veiga, F.; Figueiredo, I.V.; Jones, J.; Soares, A.F.; Nunes, P.M.; Damg\\'e, C.; Carvalho, R.A.

    2012-01-01

    The purpose of this study was to evaluate hepatic glucose metabolism of diabetic induced rats after a daily oral load of insulin nanoparticles over 2 weeks. After the 2-week treatment, an oral glucose tolerance test was performed with [U-‘‘C] glucose and ‘H2O. Plasma glucose ‘H and ‘‘C enrichments w

  14. Effects of pituitary hormone deficiency on growth and glucose metabolism of the sheep fetus.

    Science.gov (United States)

    Fowden, A L; Forhead, A J

    2007-10-01

    Pituitary hormones are essential for normal growth and metabolic responsiveness after birth, but their role before birth remains unclear. This study examined the effects of hypophysectomizing fetal sheep on their growth and glucose metabolism during the late normal and extended periods of gestation, and on their metabolic response to maternal fasting for 48 h near term. Fetal hypophysectomy reduced crown rump length (CRL), limb lengths, and body weight but increased ponderal index relative to controls near normal term. It also lowered the daily rate of crown rump length increment uniformly from 35 d before, to 20 d after normal term. Hypophysectomized (HX) fetuses had normal weight-specific rates of umbilical uptake, utilization, and oxidation of glucose but lower rates of umbilical oxygen uptake than controls near term. All these metabolic rates were significantly less in HX fetuses during the extended period of gestation than in HX and intact fetuses near normal term. In contrast to controls, glucogenesis was negligible in HX fetuses during maternal fasting. Consequently, the rate of glucose utilization decreased significantly in fasted HX but not intact fetuses. Conversely, the rate of CO(2) production from glucose carbon decreased in fasted intact but not HX fetuses. Fetal hypophysectomy also prevented the fasting-induced increases in plasma cortisol and norepinephrine concentrations seen in controls. These findings demonstrate that the pituitary hormones are important in regulating the growth rate and adaptive responses of glucose metabolism to undernutrition in fetal sheep. They also suggest that fetal metabolism is altered when gestational length is extended.

  15. Cerebral metabolism in dogs assessed by (18)F-FDG PET: a pilot study to understand physiological changes in behavioral disorders in dogs.

    Science.gov (United States)

    Irimajiri, Mami; Miller, Michael A; Green, Mark A; Jaeger, Christine B; Luescher, Andrew U; Hutchins, Gary D

    2010-01-01

    The positron emission tomography (PET) imaging technique, which is utilized in human behavior and psychiatric disorder research, was performed on the brains of clinically normal mixed breed dogs, 3 hound-type (long floppy ears) mixed breed dogs and 3 non-hound retriever-type mixed breed dogs. Glucose metabolism was obtained with F-18 fluorodeoxyglucose (FDG), and quantitative analysis was performed by standardized uptake value (SUV) measurement. Magnetic resonance (MR) images were obtained in each dog, and these images were superimposed on PET images to identify anatomical locations. The glucose metabolism in each region of interest was compared between the three hound-type dogs and 3 non-hound-type dogs. The two anatomically different types of dog were compared to assess whether breed-typical behavioral tendencies (e.g., sniffing behavior in hound-type dogs, staring and retrieving in Labrador-type dogs) are reflected in baseline brain metabolic activity. There were no significant differences between the hound-type dogs and non-hound-type dogs in cerebral SUV values. These data might serve as normal canine cerebral metabolism data for FDG PET studies in dogs and form the basis for investigations into behavioral disorders in dogs such as compulsive disorder, anxiety disorders and cognitive dysfunction.

  16. 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.

  17. 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.

  18. Cerebral oxygen metabolism in patients with early Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Østergaard, Karen;

    2012-01-01

    AIM: Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO(2)). To test this hypothesis, we compared CMRO(2...

  19. Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

    Directory of Open Access Journals (Sweden)

    Hill Nathan R

    2010-12-01

    Full Text Available Abstract Background Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM and impaired glucose metabolism (IGM. Methods Forty-five severely obese adults (36 women without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS and pancreatic beta-cell function (HOMA-B. Results Both increases in apnea-hypopnea index (AHI and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003. In subjects with NGM (n = 30, OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; P = 0.001 in women with NGM and with IL-6 (rho=-0.55; P = 0.035 in women with IGM (n = 15 matched individually for age, adiposity, and AHI. Conclusions OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly

  20. Brazilein inhibits neuronal inflammation induced by cerebral ischemia and oxygen-glucose deprivation through targeting NOD2 expression.

    Science.gov (United States)

    Yan, Xiao-Jin; Chai, Yu-Shuang; Yuan, Zhi-Yi; Wang, Xin-Pei; Jiang, Jing-Fei; Lei, Fan; Xing, Dong-Ming; DU, Li-Jun

    2016-05-01

    Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.

  1. 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.

  2. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain

    OpenAIRE

    2016-01-01

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography...

  3. Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation

    Science.gov (United States)

    Carneiro, Lionel; Geller, Sarah; Hébert, Audrey; Repond, Cendrine; Fioramonti, Xavier; Leloup, Corinne; Pellerin, Luc

    2016-01-01

    Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis. PMID:27708432

  4. Simultaneous utilization of glucose and gluconate in Penicillium chrysogenum during overflow metabolism.

    Science.gov (United States)

    Schmitz, Katja; Peter, Vivien; Meinert, Sabine; Kornfeld, Georg; Hardiman, Timo; Wiechert, Wolfgang; Noack, Stephan

    2013-12-01

    The filamentous fungus Penicillium chrysogenum is one of the most important production organism for β-lactam antibiotics, especially penicillin. A specific feature of P. chrysogenum is the formation of gluconate as the primary overflow metabolite under non-limiting growth on glucose. Gluconate can be formed extracellularly by the enzyme glucose oxidase (GOD) that shows high activities under glucose excess conditions. Currently, it is assumed that under these conditions glucose is the preferred carbon substrate for P. chrysogenum and gluconate consumption first starts after glucose becomes limiting. Here, we specifically address this hypothesis by combining batch cultivation experiments on defined glucose media, time-dependent GOD activity measurements, and (13)C-tracer studies. Our data prove that both substrates are metabolized simultaneously independent from the actual glucose concentration and therefore suggest that no distinct mechanism of carbon catabolite repression exists for gluconate in P. chrysogenum. Moreover, gluconate consumption does not interfere with penicillin V production by repression of the penicillin genes. Finally, by following a model-driven approach the specific uptake rates for glucose and gluconate were quantified and found to be significantly higher for gluconate. In summary, our results show that P. chrysogenum metabolizes gluconate directly and at high rates making it an interesting alternative carbon source for production purposes.

  5. Cerebral perfusion and metabolism in resuscitated patients with severe post-hypoxic encephalopathy

    NARCIS (Netherlands)

    Schaafsma, A.; de Jong, B M; Bams, J.L.; Haaxma-Reiche, H; Pruim, J; Zijlstra, J G

    2003-01-01

    Positron emission tomography (PET) was used for the study of regional cerebral perfusion and metabolism in eight patients with severe post-hypoxic encephalopathy, caused by cardiac arrest and resulting in a coma lasting for at least 24 h. Using this method, we aimed to identify regional vulnerabilit

  6. Neuroendocrinology: Electromagnetogenetic Control over Feeding and Glucose Metabolism.

    Science.gov (United States)

    Ruud, Johan; Brüning, Jens C

    2016-06-06

    Cutting-edge experiments show a new means to control the activity of specifically genetically targeted neurons in the hypothalamus using electromagnetic force. At the flip of a switch, the system bidirectionally regulates feeding behavior and glucose homeostasis, demonstrating wireless control over deep brain regions and their strong influence over energy balance.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Bruheim, Per; Nielsen, Jens

    2004-01-01

    primary carbon metabolism in further detail, Nonomuraea was cultivated with [1-C-13] glucose as the only carbon source and the C-13-labeling patterns of proteinogenic amino acids were determined by GC-MS analysis. Through this method, the fluxes in the central carbon metabolism during balanced growth were......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...

  9. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Fisher, James P; Young, Colin N;

    2010-01-01

    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral...... metabolism (from arterial and internal jugular venous O(2), glucose and lactate differences), as well as the middle cerebral artery mean blood velocity (MCA V(mean); transcranial Doppler ultrasound) during a sustained static handgrip contraction at 40% of maximal voluntary contraction (n = 9) and the MCA V...... abolished by glycopyrrolate (P perfusion without affecting the cerebral metabolic rate for oxygen....

  10. Sex-related differences in peripheral glucose metabolism in normal subjects.

    Science.gov (United States)

    Paula, F J; Pimenta, W P; Saad, M J; Paccola, G M; Piccinato, C E; Foss, M C

    1990-01-01

    The metabolic response of muscle tissue to glucose ingestion was studied in 10 normal men (M) and women (F) by using the forearm balance technique and indirect calorimetry simultaneously. During the 3 hours after a 75 g--oral glucose load, glucose uptake per unit muscle mass was significantly higher in women than in men, F = 187.3 +/- 26.9 vs M = 116.7 +/- 9.5 mg/100 g forearm muscle (P less than 0.05). A significant difference in muscle glucose fate was also observed since the amount of glucose utilized through a nonoxidative pathway was significantly higher in women, F = 84.5 +/- 2.6% (161.8 +/- 27.3 mg/100 g forearm muscle) vs M = 75.3 +/- 2.2% (87.2 +/- 8.6 mg/100 g forearm muscle) (P less than 0.05), whereas the amount of glucose oxidized in relation to glucose uptake was significantly higher in men, M = 24.7 +/- 2.2% (28.2 +/- 3.2 mg/100 g forearm muscle) vs F = 15.5 +/- 2.6% (27.8 +/- 5.4 mg/100 g forearm muscle) (P less than 0.05). No significant differences in insulin response to glucose ingestion were detected between groups. The women showed greater suppression of serum free fatty acids (FFA) levels in relation to basal levels than men. We conclude that: 1) after ingesting 75 g glucose, normal women showed greater glucose uptake per unit muscle mass than normal men, 2) for 3 hours after the ingestion of 75 g glucose, the predominant tendency toward utilizing glucose by a nonoxidative pathway is more marked in normal women than in normal men, and 3) the higher glucose uptake per unit muscle mass in the female group in the presence of an insulin response not significantly different from that of the male group suggests that muscle insulin sensitivity is greater in normal women.

  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. Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study

    DEFF Research Database (Denmark)

    Bartek, Jiri; Thelin, Eric Peter; Ghatan, Per Hamid;

    2016-01-01

    INTRODUCTION: Patients suffering from acute bacterial meningitis (ABM) with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP) guided therapy. By using intracranial microdialysis (MD) to monitor cerebral metabolism......) guided therapy. Serum biomarkers were obtained at admission and every 12 hours. The MD parameters glucose, lactate, pyruvate and glycerol were analyzed. Outcome was assessed at 12-55 months after discharge from hospital. Mann-Whitney U-Test and Wilcoxon matched-pairs signed rank test were applied...

  14. 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...

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

    OpenAIRE

    Vijayalakshmi Varma; Boros, László G; Nolen, Greg T.; Ching-Wei Chang; Martin Wabitsch; Beger, Richard D.; Jim Kaput

    2015-01-01

    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 asso...

  16. 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.

  17. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy

    Science.gov (United States)

    Imasawa, Toshiyuki; Obre, Emilie; Bellance, Nadège; Lavie, Julie; Imasawa, Tomoko; Rigothier, Claire; Delmas, Yahsou; Combe, Christian; Lacombe, Didier; Benard, Giovanni; Claverol, Stéphane; Bonneu, Marc; Rossignol, Rodrigue

    2017-01-01

    Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)–dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content. Conversely, when podocytes were cultured in high glucose (20 mM), stepwise oxidative phosphorylation biogenesis was aborted, and a glycolytic switch occurred, with consecutive lactic acidosis. Expression of the master regulators of oxidative metabolism transcription factor A mitochondrial, PGC-1α, AMPK, and serine–threonine liver kinase B1 was altered by high glucose, as well as their downstream signaling networks. Focused transcriptomics revealed that myocyte-specific enhancer factor 2C (MEF2C) and myogenic factor 5 (MYF5) expression was inhibited by high glucose levels, and endoribonuclease-prepared small interfering RNA–mediated combined inhibition of those transcription factors phenocopied the glycolytic shift that was observed in high glucose conditions. Accordingly, a reduced expression of MEF2C, MYF5, and PGC-1α was found in kidney tissue sections that were obtained from patients with diabetic nephropathy. These findings obtained in human samples demonstrate that MEF2C-MYF5–dependent bioenergetic dedifferentiation occurs in podocytes that are confronted with a high-glucose milieu.—Imasawa, T., Obre, E., Bellance, N., Lavie, J., Imasawa, T., Rigothier, C., Delmas, Y., Combe, C., Lacombe, D., Benard, G., Claverol, S., Bonneu, M., Rossignol, R. High glucose repatterns human podocyte energy

  18. Complex Patterns of Metabolic and Ca2+ Entrainment in Pancreatic Islets by Oscillatory Glucose

    DEFF Research Database (Denmark)

    Pedersen, Morten Gram; Mosekilde, Erik; Polonsky, Kenneth S.

    2013-01-01

    fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) in islet Ca2+ , NAD(P)H, and mitochondrial membrane potential. To our knowledge, this is the first......Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca2+in pancreatic islets. Periodic variations in glucose can entrain islet Ca2+ and insulin secretion, possibly promoting interislet synchronization. Here, we used...... demonstration of metabolic entrainment in islets, and we found that entrainment of metabolic oscillations requires voltage-gated Ca2+ influx. We identified diverse patterns of 1:2 entrainment and showed that islet synchronization during entrainment involves adjustments of both oscillatory phase and period. All...

  19. Akt Requires Glucose Metabolism to Suppress Puma Expression and Prevent Apoptosis of Leukemic T Cells*

    Science.gov (United States)

    Coloff, Jonathan L.; Mason, Emily F.; Altman, Brian J.; Gerriets, Valerie A.; Liu, Tingyu; Nichols, Amanda N.; Zhao, Yuxing; Wofford, Jessica A.; Jacobs, Sarah R.; Ilkayeva, Olga; Garrison, Sean P.; Zambetti, Gerard P.; Rathmell, Jeffrey C.

    2011-01-01

    The PI3K/Akt pathway is activated in stimulated cells and in many cancers to promote glucose metabolism and prevent cell death. Although inhibition of Akt-mediated cell survival may provide a means to eliminate cancer cells, this survival pathway remains incompletely understood. In particular, unlike anti-apoptotic Bcl-2 family proteins that prevent apoptosis independent of glucose, Akt requires glucose metabolism to inhibit cell death. This glucose dependence may occur in part through metabolic regulation of pro-apoptotic Bcl-2 family proteins. Here, we show that activated Akt relies on glycolysis to inhibit induction of Puma, which was uniquely sensitive to metabolic status among pro-apoptotic Bcl-2 family members and was rapidly up-regulated in glucose-deficient conditions. Importantly, preventing Puma expression was critical for Akt-mediated cell survival, as Puma deficiency protected cells from glucose deprivation and Akt could not readily block Puma-mediated apoptosis. In contrast, the pro-apoptotic Bcl-2 family protein Bim was induced normally even when constitutively active Akt was expressed, yet Akt could provide protection from Bim cytotoxicity. Up-regulation of Puma appeared mediated by decreased availability of mitochondrial metabolites rather than glycolysis itself, as alternative mitochondrial fuels could suppress Puma induction and apoptosis upon glucose deprivation. Metabolic regulation of Puma was mediated through combined p53-dependent transcriptional induction and control of Puma protein stability, with Puma degraded in nutrient-replete conditions and long lived in nutrient deficiency. Together, these data identify a key role for Bcl-2 family proteins in Akt-mediated cell survival that may be critical in normal immunity and in cancer through Akt-dependent stimulation of glycolysis to suppress Puma expression. PMID:21159778

  20. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

    Science.gov (United States)

    Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

    2014-04-01

    As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

  1. 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...

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

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

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

  3. 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.

  4. Perinatal exposure to perfluorooctane sulfonate affects glucose metabolism in adult offspring.

    Directory of Open Access Journals (Sweden)

    Hin T Wan

    Full Text Available Perfluoroalkyl acids (PFAAs are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0 were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21. To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders.

  5. Effects of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in bovine mammary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hongyun Liu

    Full Text Available As the main precursor for lactose synthesis, large amounts of glucose are required by lactating dairy cows. Milk yield greatly depends on mammary lactose synthesis due to its osmoregulatory property for mammary uptake of water. Thus, glucose availability to the mammary gland could be a potential regulator of milk production. In the present study, the effect of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in vitro was investigated. Bovine mammary epithelial cells (BMEC were treated for 12 h with various concentrations of glucose (2.5, 5, 10 or 20 mmol/L. The higher concentrations of glucose (10-20 mmol/L did not affect the mRNA expression of acetyl-CoA carboxylase, diacyl glycerol acyl transferase, glycerol-3 phosphate acyl transferase and α-lactalbumin, whereas fatty acid synthase, sterol regulatory element binding protein-1 and beta-1, 4-galactosyl transferase mRNA expression increased at 10 mmol/L and then decreased at 20 mmol/L. The content of lactose synthase increased with increasing concentration of glucose, with addition of highest value at 20 mmol/L of glucose. Moreover, the increased glucose concentration stimulated the activities of pyruvate kinase and glucose-6-phosphate dehydrogenase, and elevated the energy status of the BMEC. Therefore, it was deduced that after increasing glucose availability, the extra absorbed glucose was partitioned to entering the synthesis of milk fat and lactose by the regulation of the mRNA expression of key genes, promoting glucose metabolism by glycolysis and pentose phosphate pathway as well as energy status. These results indicated that the sufficient availability of glucose in BMEC may promote glucose metabolism, and affect the synthesis of milk composition.

  6. 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...... in patients with psoriasis has only been sparsely investigated. Previous studies are based on fasting blood samples analysed for glucose and insulin or various forms of glucose and/or insulin challenges.(5-11) The results are generally difficult to compare due to methodological differences and limitations...

  7. The effect of PCSK1 variants on waist, waist-hip ratio and glucose metabolism is modified by sex and glucose tolerance status

    DEFF Research Database (Denmark)

    Gjesing, Anette P; Vestmar, Marie A; Jørgensen, Torben;

    2011-01-01

    Background: We aimed to evaluate the effects of the G-allele of rs6232 and the C-allele of rs6235 within PCSK1 on measures of body fat and glucose homeostasis in Danish individuals and to assess interactions of genotypes with age, sex and glucose tolerance status. Data were included in meta-analy...... composition which may be modified by sex, whereas the effect of rs6235 C-allele on fasting and stimulated circulating plasma glucose and hormone levels may be influenced by glucose tolerance status.......-allele was associated nominally with a 0.6% (0.1–1%, p = 0.01) reduction in fasting glucose, it interacted with glucose tolerance status for traits related to glucose metabolism and analysis among individuals having abnormal glucose tolerance revealed a 5% (20.7–9%, p = 0.02) elevated level of acute insulin response...

  8. 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.

  9. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    Directory of Open Access Journals (Sweden)

    Steven Moore

    2015-05-01

    Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

  10. 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

  11. 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

    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....... to increase with increasing specific growth rate but at a much lower level than previously reported for Bacillus subtilis. Two futile cycles in the pyruvate metabolism were included in the metabolic network. A substantial flux in the futile cycle involving malic enzyme was estimated, whereas only a very small......Using C-13-labeled glucose fed to the facultative alkalophilic Bacillus clausii producing the alkaline serine protease Savinase, the intracellular fluxes were quantified in continuous cultivation and in batch cultivation on a minimal medium. The flux through the pentose phosphate pathway was found...

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

    Directory of Open Access Journals (Sweden)

    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. 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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    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. Age-related alterations in behavioral and cerebral metabolic responses to the serotonin agonist meta-chlorophenylpiperazine in rats.

    Science.gov (United States)

    Freo, U; Rapoport, S I; Soncrant, T T

    1991-01-01

    To determine the functional relevance of the age-related neurochemical changes that occur in brain serotonin systems during aging, we measured the effects of the serotonin receptor agonist meta-chlorophenylpiperazine (MCPP) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) in awake rats. rCMRglc was determined in 74 regions of Fischer-344 rats aged 3, 12 and 24 months, at 15 and 90 min after MCPP 2.5 mg/kg IP, using the quantitative, autoradiographic [14C]2-deoxy-D-glucose technique. The time-course of motor performance following MCPP was assessed with a rotating rod. MCPP impaired motor performance in all ages maximally at 15-30 min. Three-month-old rats recovered completely within 60 min, whereas 12-month-old animals exhibited partial recovery and 24-month-old rats did not recover by 120 min. At 15 min after MCPP, rCMRglc was reduced in 51 of the 74 studied regions (overall decrease, 20%) of 3-month-old rats, in 21 regions (13% decrease) of 12-month-old rats and in 14 regions (2% decrease) of 24-month-old animals. Similar MCPP brain concentrations were achieved at 15 min in rats of all ages. The results suggest that the functional integrity of serotonergic transmission is reduced in aged rats and that the dysregulation is presynaptic.

  17. Cerebral metabolic responses to meta-chlorophenylpiperazine are reduced during its chronic administration to young and aged rats.

    Science.gov (United States)

    Freo, U; Larson, D M; Soncrant, T T

    1993-01-01

    The effects of the 5-HT agonist meta-chlorophenylpiperazine (MCPP) on regional cerebral metabolic rates for glucose (rCMRglc) were measured in 3- and 24-month-old rats that were not pretreated or were pretreated for 2 weeks with continuous infusion of saline or MCPP. rCMRglc were measured using the quantitative autoradiographic [14C]2-deoxy-D-glucose technique in 71 brain regions at 15 min after acute administration of MCPP 2.5 mg/kg. In the absence of chronic pretreatment, intraperitoneal MCPP 2.5 mg/kg produced widespread rCMRglc reductions (41 brain areas) in 3-month-old rats and more limited rCMRglc decreases (8 brain areas) in 24-month-old rats. After chronic treatment, MCPP failed to reduce rCMRglc in any region of either group of rats. These findings indicate that mechanisms of downregulation of response to MCPP are functional in young and aged rats and suggest that the age-related reduction in rCMRglc responses to acute MCPP in non-pretreated animals may be due to compensation for age-related losses of 5-HT terminals.

  18. Sexual Dimorphism in Glucose and Lipid Metabolism during Fasting, Hypoglycemia, and Exercise

    OpenAIRE

    Hedrington, Maka S.; Davis, Stephen N.

    2015-01-01

    Sexually dimorphic physiologic responses occur during fasting, hypoglycemia, and exercise. The areas covered in this mini review include studies that have used isotopic tracer methods and/or euglycemic clamp studies to investigate substrate metabolism during the above common physiologic stress. Women have greater reliance on lipid metabolism during fasting, hypoglycemia, and exercise while men exhibit preference of carbohydrate utilization. Plasma glucose concentrations were shown to be lower...

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

    Science.gov (United States)

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

    2015-03-01

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

  1. 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.

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

    Science.gov (United States)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus S.; 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; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

    2013-01-01

    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) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

  3. Glucose metabolism in completed suicide: a forensic-pathological pilot study

    Science.gov (United States)

    Forsman, Jonas; Keltanen, Terhi; Liberg, Benny; Sajantila, Antti; Masterman, Thomas; Lindroos, Katarina

    2017-01-01

    Aim To determine whether antemortem blood levels of glycated hemoglobin (HbA1c) and glucose predict completed suicide and, by extension, whether markers of glucose metabolism might be associated with a prosuicidal trait or state. Method From consecutively performed autopsies, samples of blood and vitreous humor from 17 suicide victims and 27 non-suicide controls were compared with regard to levels of glucose, lactate, and HbA1c. Results Mean HbA1c was higher and mean estimated blood glucose was lower among suicide victims, although tests revealed no significant differences (P = 0.171 and P = 0.395, respectively). HbA1c levels exceeding 48.0 mmol/mol, which were indicative of persistent hyperglycemia, were twice as common in suicide victims (59% vs 30%; P = 0.068). Conclusion The finding of this pilot study suggest that deranged glucose metabolism may reflect biological events antecedent to, or concomitant with, completed suicide, with the following clinical implications: recurring hyperglycemia due to defective glucose transport, which may give rise to depression and suicidal ideation, and elevated HbA1c levels, which may represent an assayable correlate to neurobiological conditions predisposing to suicide. PMID:28252873

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

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    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.

  5. 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.

  6. Quantification of pathways of glucose utilization and balance of energy metabolism of rabbit reticulocytes.

    Science.gov (United States)

    Siems, W; Müller, M; Dumdey, R; Holzhütter, H G; Rathmann, J; Rapoport, S M

    1982-06-01

    In this work it is demonstrated that glucose constitutes the main substrate of energy metabolism of rabbit reticulocytes under aerobic conditions in the presence of 5 mM glucose. Amino acids and fatty acids are minor sources of energy. The shares of processes utilizing glucose in reticulocytes were estimated from tracer experiments. A new mathematical technique used permits the derivation of closed terms for the specific radioactivity of single positions of C atoms of the metabolites of the citrate cycle. By means of regression analysis, the undetermined flux rates in the citrate cycle were calculated. On the basis of the data an overall balance sheet of glucose utilization and of ATP generation is given. About 45% of the glucose of reticulocytes is catabolized via the citrate cycle, about the same percentage yields lactate. Only 2% of the glucose was oxidized in the oxidative pentose pathway whereas the remainder is used for the formation of serine and glycine required for hemoglobin synthesis. These results are related to knowledge about the main processes utilizing ATP in reticulocytes, i.e. the synthesis of hemoglobin and the energy-dependent proteolysis. Our approach to the investigation of metabolic relations in the reticulocytes can be applied to other tissues in which equilibria between large metabolite pools play a role.

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

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    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.

  8. 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

  9. Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

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    Sugiura, Yuki; Honda, Kurara; Kondo, Koki; Miura, Masayuki

    2017-01-01

    Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flow into the pentose phosphate pathway via suppression of the key glycolytic enzymes PFK-1 and aldolase during CB. Concomitantly, embryos exhibited an increase in lactate pool size and in the fractional contribution of glycolysis to lactate biosynthesis. Imaging mass spectrometry visualized lactate-rich tissues, such as the dorsal or posterior neural tube, somites and head mesenchyme. Furthermore, we found that the heterochronic gene Lin28a could act as a regulator of the metabolic changes observed during CB. Perturbation of glucose metabolism rewiring by suppressing Lin28a downregulation resulted in perinatal lethality. Thus, our work demonstrates that developing embryos rewire glucose metabolism following CB for normal development. PMID:28049690

  10. Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

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    Vu Thanh Nguyen

    2016-01-01

    Full Text Available The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Besides the exogenous stress response, Nrf2 has been found to regulate numerous cellular functions, including protein turnover and glucose metabolism; however, the evolutionary origins of these functions remain unknown. In the present study, we searched for novel target genes associated with the zebrafish Nrf2 to answer this question. A microarray analysis of zebrafish embryos that overexpressed Nrf2 revealed that 115 candidate genes were targets of Nrf2, including genes encoding proteasome subunits and enzymes involved in glucose metabolism. A real-time quantitative PCR suggested that the expression of 3 proteasome subunits (psma3, psma5, and psmb7 and 2 enzymes involved in glucose metabolism (pgd and fbp1a were regulated by zebrafish Nrf2. We thus next examined the upregulation of these genes by an Nrf2 activator, diethyl maleate, using Nrf2 mutant zebrafish larvae. The results of real-time quantitative PCR and whole-mount in situ hybridization showed that all of these 5 genes were upregulated by diethyl maleate treatment in an Nrf2-dependent manner, especially in the liver. These findings implied that the Nrf2-mediated regulation of the proteasome subunits and glucose metabolism is evolutionarily conserved among vertebrates.

  11. 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...

  12. 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

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

    NARCIS (Netherlands)

    Jha, P.K.

    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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism...

  15. 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 ...

  16. 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...... 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...... tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course...

  17. Influence of rotating magnetic field on cerebral infarction volume, cerebral edema and free radicals metabolism after cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Liu; Zhiqiang Zhang; Lixin Zhang

    2006-01-01

    BACKGROUND: It has shown that magnetic field can improve blood circulation, decrease blood viscosity, inhibit free radicals, affect Ca2+ flow in nerve cells, control inflammatory and immunological reaction, and accelerate nerve cell regeneration. In addition, protective effect of magnetic field, which acts as an iatrophysics, on ischemic brain tissues has been understood gradually.OBJECTIVE: To investigate the effects of rotating magnetic field (RMF) on volume of cerebral infarction,cerebral edema and metabolism of free radicals in rats after cerebral ischemia/reperfusion injury.DESIGN: Randomized controlled animal study.SETTING: Rehabilitation Center of disabled children, Liaoniang; Department of Rehabilitation, the Second Affiliated Hospital, China Medical University; Department of Rehabilitation Physiotherapy, the First Affiliated Hospital, China Medical University.MATERIALS: A total of 70 healthy Wistar rats aged 18-20 weeks of both genders were selected and randomly divided into 3 groups: sham operation group with 12 rats, control group with 20 rats and treatment group with 38 rats. The treatment group included 4 time points: immediate reperfusion with 6 ones, 6-hour reperfusion with 20 ones, 12-hour reperfusion with 6 ones and 18-hour reperfusion with 6 rats. Main instruments were detailed as follows: magnetic head of rotating magnetic device was 6 cm in diameter; magnetic induction intensity at the surface of magnetic head was 0.25 T in silence; the maximal magnetic induction intensity was 0.09 T at the phase of rotation; the average rotating speed was 2500 r per minute.METHODS: The experiment was carried out in the China Medical University in March 2003. Focal cerebral ischemic animal models were established with modified Longa's method. Operation was the same in the sham operation, but the thread was inserted as 10 mm. Neurologic impairment was assessed with 5-rating method to screen out cases. Those survivals with grade 1 and grade 2 after ischemia for 2

  18. Germinated Pigmented Rice (Oryza Sativa L. cv. Superhongmi Improves Glucose and Bone Metabolisms in Ovariectomized Rats

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    Soo Im Chung

    2016-10-01

    Full Text Available The effect of germinated Superhongmi, a reddish brown pigmented rice cultivar, on the glucose profile and bone turnover in the postmenopausal-like model of ovariectomized rats was determined. The ovariectomized Sprague-Dawley rats were randomly divided into three dietary groups (n = 10: normal control diet (NC and normal diet supplemented with non-germinated Superhongmi (SH or germinated Superhongmi (GSH rice powder. After eight weeks, the SH and GSH groups showed significantly lower body weight, glucose and insulin concentrations, levels of bone resorption markers and higher glycogen and 17-β-estradiol contents than the NC group. The glucose metabolism improved through modulation of adipokine production and glucose-regulating enzyme activities. The GSH rats exhibited a greater hypoglycemic effect and lower bone resorption than SH rats. These results demonstrate that germinated Superhongmi rice may potentially be useful in the prevention and management of postmenopausal hyperglycemia and bone turnover imbalance.

  19. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw; Stridh, Malin H; Zaganas, Ioannis; Skytt, Dorte M; Schousboe, Arne; Bak, Lasse K; Enard, Wolfgang; Pääbo, Svante; Waagepetersen, Helle S

    2017-03-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1 and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation and supports the TCA cycle during energy-demanding processes such as high intensity glutamatergic signaling. However, little is known about how expression of hGDH2 affects the handling of glutamate and TCA cycle metabolism in astrocytes. Therefore, we cultured astrocytes from cerebral cortical tissue of hGDH2-expressing transgenic mice. We measured glutamate uptake and metabolism using [(3) H]glutamate, while the effect on metabolic pathways of glutamate and glucose was evaluated by use of (13) C and (14) C substrates and analysis by mass spectrometry and determination of radioactively labeled metabolites including CO2 , respectively. We conclude that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and aglycemia. Additionally, hGDH2 expression increased utilization of branched-chain amino acids (BCAA) during aglycemia and caused a general decrease in oxidative glucose metabolism. We speculate, that expression of hGDH2 allows astrocytes to spare glucose and utilize BCAAs during substrate shortages. These findings support the proposed role of hGDH2 in astrocytes as an important fail-safe during situations of intense glutamatergic activity. GLIA 2017;65:474-488.

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

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    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.

  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. APP metabolism regulates tau proteostasis in human cerebral cortex neurons

    OpenAIRE

    Steven Moore; Evans, Lewis D.B.; Therese Andersson; Erik Portelius; James Smith; Tatyana B. Dias; Nathalie Saurat; Amelia McGlade; Peter Kirwan; Kaj Blennow; John Hardy; Henrik Zetterberg; Frederick J. Livesey

    2015-01-01

    This is the final version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S2211124715003599. Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, a...

  3. Glucose metabolism in batch and continuous cultures of Gluconacetobacter diazotrophicus PAL 3.

    Science.gov (United States)

    Luna, María F; Bernardelli, Cecilia E; Galar, María L; Boiardi, José L

    2006-03-01

    Periplasmic glucose oxidation (by way of a pyrrolo-quinoline-quinone [PQQ]-linked glucose dehydrogenase [GDH]) was observed in continuous cultures of Gluconacetobacter diazotrophicus regardless of the carbon source (glucose or gluconate) and the nitrogen source (N(2) or NH(3)). Its synthesis was stimulated by conditions of high energetic demand (i.e., N(2)-fixation) and/or C-limitation. Under C-excess conditions, PQQ-GDH synthesis increased with the glucose concentration in the culture medium. In batch cultures, PQQ-GDH was actively expressed in very early stages with higher activities under conditions of N(2)-fixation. Hexokinase activity was almost absent under any culture condition. Cytoplasmic nicotinamide adenine dinucleotide (NAD)-linked glucose dehydrogenase (GDH) was expressed in continuous cultures under all tested conditions, and its synthesis increased with the glucose concentration. In contrast, low activities of this enzyme were detected in batch cultures. Periplasmic oxidation, by way of PQQ-GDH, seems to be the principal pathway for metabolism of glucose in G. Diazotrophicus, and NAD-GDH is an alternative route under certain environmental conditions.

  4. Effect of breakfast skipping on diurnal variation of energy metabolism and blood glucose.

    Science.gov (United States)

    Kobayashi, Fumi; Ogata, Hitomi; Omi, Naomi; Nagasaka, Shoichiro; Yamaguchi, Sachiko; Hibi, Masanobu; Tokuyama, Kumpei

    2014-01-01

    Epidemiological studies suggest an association between breakfast skipping and body weight gain, insulin resistance or type 2 diabetes. Time when meal is consumed affects postprandial increase in energy expenditure and blood glucose, and breakfast skipping may reduce 24 h energy expenditure and elevate blood glucose level. The present study evaluated the effect of breakfast skipping on diurnal variation of energy metabolism and blood glucose. The skipped breakfast was compensated by following big meals at lunch and supper. In a randomized repeated-measure design with or without breakfast, eight males stayed twice in a room-size respiratory chamber. Blood glucose was recorded with a continuous glucose monitoring system. Breakfast skipping did not affect 24 h energy expenditure, fat oxidation and thermic effect of food, but increased overall 24 h average of blood glucose (83 ± 3 vs 89 ± 2 mg/dl, P breakfast skipping. These observations suggest that changes in glucose homeostasis precede that of energy balance, in the potential sequence caused by breakfast skipping, if this dietary habit has any effect on energy balance.:

  5. Regional changes in glucose metabolism during brain development from the age of 6 years.

    Science.gov (United States)

    Van Bogaert, P; Wikler, D; Damhaut, P; Szliwowski, H B; Goldman, S

    1998-07-01

    Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) studies of 42 subjects ages 6 to 38 years were analyzed using statistical parametric mapping to identify age-related changes in regional distribution of glucose metabolism adjusted for global activity. Whereas adults were normal volunteers, children had idiopathic epilepsy. We studied polynomial expansions of age to identify nonlinear effects and found that adjusted glucose metabolism varied very significantly in the thalamus and the anterior cingulate cortex and to a lesser degree in the basal ganglia, the mesencephalon, and the insular, posterior cingulate, frontal, and postcentral cortices. Regression plots slowed that the best fit was not linear: adjusted glucose metabolism increased mainly before the age of 25 years and then remained relatively stable. Effects persisted when anti-epileptic drug intake and sleep during the FDG uptake were considered as confounding covariates. To determine if the metabolic changes observed were not due to the epileptic condition of the children, PET data obtained in adults with temporal lobe epilepsy were compared with those in our group of normal adult subjects, resulting in the absence of mapping in the age-related regions. This study suggests that brain maturation from the age of 6 years gives rise to a relative increase of synaptic activities in the thalamus, possibly as a consequence of improved corticothalamic connections. Increased metabolic activity in the anterior cingulate cortex is probably related to these thalamic changes and suggests that the limbic system is involved in the processes of brain maturation.

  6. Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome.

    Science.gov (United States)

    Yamada, Yoshiji; Kato, Kimihiko; Oguri, Mitsutoshi; Yoshida, Tetsuro; Yokoi, Kiyoshi; Watanabe, Sachiro; Metoki, Norifumi; Yoshida, Hidemi; Satoh, Kei; Ichihara, Sahoko; Aoyagi, Yukitoshi; Yasunaga, Akitomo; Park, Hyuntae; Tanaka, Masashi; Nozawa, Yoshinori

    2008-06-01

    Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (PA (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.

  7. Metabolic effects of perinatal asphyxia in the rat cerebral cortex.

    Science.gov (United States)

    Souza, Samir Khal; Martins, Tiago Leal; Ferreira, Gustavo Dias; Vinagre, Anapaula Sommer; Silva, Roselis Silveira Martins da; Frizzo, Marcos Emilio

    2013-03-01

    We reported previously that intrauterine asphyxia acutely affects the rat hippocampus. For this reason, the early effects of this injury were studied in the cerebral cortex, immediately after hysterectomy (acute condition) or following a recovery period at normoxia (recovery condition). Lactacidemia and glycemia were determined, as well as glycogen levels in the muscle, liver and cortex. Cortical tissue was also used to assay the ATP levels and glutamate uptake. Asphyxiated pups exhibited bluish coloring, loss of movement, sporadic gasping and hypertonia. However, the appearance of the controls and asphyxiated pups was similar at the end of the recovery period. Lactacidemia and glycemia were significantly increased by asphyxia in both the acute and recovery conditions. Concerning muscle and hepatic glycogen, the control group showed significantly higher levels than the asphyxic group in the acute condition and when compared with groups of the recovery period. In the recovery condition, the control and asphyxic groups showed similar glycogen levels. However, in the cortex, the control groups showed significantly higher glycogen levels than the asphyxic group, in both the acute and recovery conditions. In the cortical tissue, asphyxia reduced ATP levels by 70 % in the acute condition, but these levels increased significantly in asphyxic pups after the recovery period. Asphyxia did not affect glutamate transport in the cortex of both groups. Our results suggest that the cortex uses different energy resources to restore ATP after an asphyxia episode followed by a reperfusion period. This strategy could sustain the activity of essential energy-dependent mechanisms.

  8. 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

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

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    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.

  10. 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

  11. 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.

  12. 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.

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

    Science.gov (United States)

    Varma, Vijayalakshmi; Boros, László G; Nolen, Greg T; Chang, Ching-Wei; Wabitsch, Martin; Beger, Richard D; Kaput, Jim

    2015-06-16

    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.

  14. 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.

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

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    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.

  16. GLUCOSE AND LACTATE METABOLISM IN THE AWAKE AND STIMULATED RAT: A 13C-NMR STUDY.

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    Denys eSampol

    2013-05-01

    Full Text Available Glucose is the major energetic substrate for the brain but evidence has accumulated during the last 20 years that lactate produced by astrocytes could be an additional substrate for neurons. However, little information exists about this lactate shuttle in vivo in activated and awake animals. We designed an experiment in which the cortical barrel field (S1BF was unilaterally activated during infusion of both glucose and lactate (alternatively labeled with 13C in rats. At the end of stimulation (1h, both S1BF areas were removed and analyzed by HR-MAS NMR spectroscopy to compare glucose and lactate metabolism in the activated area versus the non-activated one. In combination with microwave irradiation, HR-MAS spectroscopy is a powerful technical approach to study brain lactate metabolism in vivo.Using in vivo 14C-2-deoxyglucose and autoradiography, we confirmed that whisker stimulation was effective since we observed a 40% increase in glucose uptake in the activated S1BF area compared to the ipsilateral one.We first determined that lactate observed on spectra of biopsies did not arise from post-mortem metabolism. 1H-NMR data indicated that during brain activation, there was an average 2.4-fold increase in lactate content in the activated area. When [1-13C]glucose+lactate were infused, 13C-NMR data showed an increase in 13C-labeled lactate during brain activation, as well as an increase in lactate C3-specific enrichment. This result demonstrates that the increase in lactate observed on 1H-NMR spectra originates from newly synthesized lactate from the labeled precursor ([1-13C]glucose. It also shows that this additional lactate does not arise from an increase in blood lactate uptake since it would otherwise be unlabeled. These results are in favor of intracerebral lactate production during brain activation in vivo, which could be a supplementary fuel for neurons.

  17. 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)

  18. 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

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

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    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.

  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. Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells.

    Science.gov (United States)

    Hansen, Fernanda; de Souza, Daniela Fraga; Silveira, Simone da Luz; Hoefel, Ana Lúcia; Fontoura, Júlia Bijoldo; Tramontina, Ana Carolina; Bobermin, Larissa Daniele; Leite, Marina Concli; Perry, Marcos Luiz Santos; Gonçalves, Carlos Alberto

    2012-12-01

    Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3 h) and long term (24 h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO(2) increased in 1 h and the conversion of glucose to lipids increased at 3 h. In addition, glycine oxidation to CO(2) and conversion of glycine to lipids increased at 1 h, whereas the incorporation of glycine in proteins decreased at 1 and 3 h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24 h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.

  2. 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.)

  3. Metabolism of biogenic amines in acute cerebral ischemia: Influence of systemic hyperglycemia

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    Milovanović Aleksandar

    2012-01-01

    Full Text Available Dopamine, norepinephrine and serotonin are biogenic amines which are transmitters of the central nervous system. The effects of ischemia on the brain parenchyma depends on many factors, such is the mechanism of blood flow interruption, velocity of the occurring blood flow interruption, duration of an ischemic episode, organization of anatomical structures of the brain blood vessels etc., which all influence the final outcome. During interruption of the brain circulation in experimental or clinical conditions, neurotransmitter metabolism, primarily of biogenic amines, is disturbed. Many researches with various experimental models of complete ischemia reported a decrease in the content of norepinephrine, dopamine and serotonin in the CNS tissue. It was proven that hyperglycemia can drastically increase cerebral injury followed by short-term cerebral ischemia. Considering the fact that biogenic amines (dopamine, norepinephrine and serotonin influence the size of neurologic damage, as well as the fact that in hyperglycemic conditions infarct size (from the morphological aspect is larger relative to normoglycemic status, the intention was to evaluate the role of biogenic amines in occurrence of damage in conditions of hyperglycemia, i.e. in the case of brain apoplexia in diabetics. Analysis of biogenic amines metabolism in states of acute hyperglycemia, as well as analysis of the effects of reversible and irreversible brain ischemia on metabolism of serotonin, dopamine and norepinephrine, showed that acute hyperglycemia slows down serotonin, dopamine and norepinephrine metabolism in the cerebral cortex and n. caudatus. Brain ischemia in normoglycemic animals by itself has no influence on biogenic amines metabolism, but the effect of ischemia becomes apparent during reperfusion. In recirculation, which corresponds to the occurrences in penumbra, release of biogenic amines is uncontrolled and increased. Brain ischemia in acute hyperglycemic animals

  4. Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients.

    Science.gov (United States)

    Molinari, F; Simonetti, V; Franzini, M; Pandolfi, S; Vaiano, F; Valdenassi, L; Liboni, W

    2014-01-01

    Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated haemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the

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

    OpenAIRE

    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...

  6. 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....

  7. 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

  8. Visceral adiposity influences glucose and glycogen metabolism in control and hyperlipidic-fed animals

    Directory of Open Access Journals (Sweden)

    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.

  9. Metabolic Characteristics of a Glucose-Utilizing Shewanella oneidensis Strain Grown under Electrode-Respiring Conditions.

    Directory of Open Access Journals (Sweden)

    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.

  10. Neurodynamics of abnormalities in cerebral metabolism and structure in schizophrenia.

    Science.gov (United States)

    Waddington, J L

    1993-01-01

    Much evidence points to the importance of intrauterine events in the etiology of schizophrenia and suggests a complex interplay between dysfunctional and intact neurons in the pathophysiology of the disorder. This article contrasts what is known of the topographies of metabolic and structural brain abnormalities in schizophrenia at differing stages of the illness. From these contrasts, a schema is elaborated by which subtle neurodevelopmental perturbation in early to middle gestation might give rise to functional and structural abnormalities that ultimately release the diagnostic symptoms of schizophrenia. An interaction between those mechanisms mediating the expression of psychosis and the initially subtle stages of normal aging is posited to act on the substrate of a brain that is already developmentally compromised. Such a process might masquerade as "progression" in the absence of any active disease directly attributable to the original etiological event.

  11. Metabolic responses to exercise on land and in water following glucose ingestion.

    Science.gov (United States)

    Kurobe, Kazumichi; Kousaka, Ayaka; Ogita, Futoshi; Matsumoto, Naoyuki

    2016-12-26

    Although aerobic exercise after a meal decreases postprandial blood glucose, the differences in glucose response between land and aquatic exercise are unclear. Thus, we examined the effect of different modes of exercise with same energy expenditure following glucose ingestion on carbohydrate metabolism. Ten healthy sedentary men (age, 22 ± 1 years) participated in this study. All subjects performed each of three exercise modes (cycling, walking and aquatic exercise) for 30 min after ingestion of a 75-g glucose solution with 1-2 weeks between trials. The exercise intensity was set at 40% of the maximum oxygen uptake that occurred during cycling. The velocity during walking and the target heart rate during aquatic exercise were predetermined in a pretest. The plasma glucose concentration at 30 min after exercise was significantly lower with aquatic exercise compared to that with cycling and walking (Pexercise modes in respiratory exchange ratio. On the other hand, serum free fatty acid concentration with aquatic exercise was significantly higher at 120 min after exercise compared with that after walking (Pexercise reduces postprandial blood glucose compared with both cycling and walking with the same energy expenditure. Aquatic exercise shows potential as an exercise prescription to prevent postprandial hyperglycaemia.

  12. Cross feeding of glucose metabolism byproducts of Escherichia coli human gut isolates and probiotic strains affect survival of Vibrio cholerae.

    Science.gov (United States)

    Sengupta, Chirantana; Ekka, Manjula; Arora, Saurabh; Dhaware, Prashant D; Chowdhury, Rukhsana; Raychaudhuri, Saumya

    2017-01-01

    Vibrio cholerae converts glucose into either acid or the neutral end product acetoin and its survival in carbohydrate enriched media is linked to the nature of the byproducts produced. It has been demonstrated in this study that Escherichia coli strain isolated from the gut of healthy human volunteers and the commonly used probiotic E. coli Nissle strain that metabolize glucose to acidic byproducts drastically reduce the survival of V. cholerae strains irrespective of their glucose sensitivity and acetoin production status. Accordingly, E. coli glucose transport mutants that produce lower amounts of acidic metabolites had little effect on the survival of V. cholerae in cocultures. Thus, cross feeding of byproducts of glucose metabolism by heterologous bacteria modulates the survival of V. cholerae in glucose rich medium suggesting that composition of the gut microbiota could influence the outcome of V. cholerae infection especially when glucose based ORS is administered.

  13. 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.

  14. High incidence of abnormal glucose metabolism in acute coronary syndrome patients at a moderate altitude: A sub-Himalayan study

    Science.gov (United States)

    Mokta, Jitender; Kumar, Subash; Ganju, Neeraj; Mokta, Kiran; Panda, Prashant Kumar; Gupta, Swatantra

    2017-01-01

    Background: Abnormal glucose metabolic status at admission is an important marker of future cardiovascular events and long-term mortality after acute coronary syndrome (ACS), whether or not they are known diabetics. Objective: The aims were to study the prevalence of abnormal glucose metabolism in ACS patients and to compare the different methods of diagnosing diabetes in ACS patients. Methods: We did a prospective study. About 250 consecutive nondiabetic patients (200 men and 50 women) with ACS admitted to a tertiary care institute of Himachal Pradesh in 1 year were enrolled. Admission plasma glucose, next morning fasting plasma glucose (FPG), A1C, and a standardized 75-g oral glucose tolerance test (OGTT) 72 h after admission were done. Glucose metabolism was categorized as normal glucose metabolism, impaired glucose metabolism (impaired fasting glucose or impaired glucose tolerance [IGT]), and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HBA1c ≥6.5%) or possibly stress diabetes (HBA1c <6.5%). A repeat OGTT after 3 months in objects with IGT and stress hyperglycemia at a time of admission was done. Results: The mean age was 54 ± 12.46 years. The mean plasma glucose at admission was 124 ± 53.96 mg/dL, and the mean FPG was 102 ± 27.07 mg/dL. The mean 2-h postglucose load concentration was 159.5 ± 56.58 mg/dL. At baseline, 95 (38%) had normal glucose metabolism, 95 (38%) had impaired glucose metabolism (IGT and or IGT) and 60 (24%) had diabetes; 48 (19.2%) were undiagnosed diabetes and 12 (4.8%) had stress hyperglycemia. At follow up 58.66% and 55.55% of patients with impaired glucose tolerance and stress hyperglycemia continued to have impaired glucose tolerance respectively. About 75 gm OGTT has highest sensitivity and specificity to diagnose diabetes, whereas A1C most specific to rule out stress hyperglycemia. Conclusions: In this small hilly state of India, abnormal glucose metabolism (previously undiagnosed diabetes and IGT) is

  15. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures

    Directory of Open Access Journals (Sweden)

    Jordà Joel

    2012-05-01

    Full Text Available Abstract Background The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production. Results The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w mix as carbon source. The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates. Conclusions Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic

  16. 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

  17. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Shanshan Sun

    2017-04-01

    Full Text Available Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD, a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

  18. Individual cerebral metabolic deficits in Alzheimer's disease and amnestic mild cognitive impairment: an FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Del Sole, Angelo; Lecchi, Michela; Lucignani, Giovanni [Unit of Nuclear Medicine, Hospital San Paolo, Institute of Radiological Sciences, University of Milan, Milan (Italy); Clerici, Francesca; Mariani, Claudio; Maggiore, Laura [University of Milan, Center for Research and Treatment on Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Clinical Sciences, ' Luigi Sacco' Hospital, Milan (Italy); Chiti, Arturo [Clinical Institute Humanitas, Nuclear Medicine Department, Milan (Italy); Mosconi, Lisa [New York University School of Medicine, Department of Psychiatry, New York, NY (United States)

    2008-07-15

    The purpose of the study was the identification of group and individual subject patterns of cerebral glucose metabolism (CMRGlu) in patients with Alzheimer's disease (AD) and with amnestic mild cognitive impairment (aMCI). [{sup 18}F]fluorodeoxyglucose positron emission tomography (PET) studies and neuropsychological tests were performed in 16 aMCI patients (ten women, age 75 {+-} 8 years) and in 14 AD patients (ten women, age 75 {+-} 9 years). Comparisons between patient subgroups and with a control population were performed using Statistical Parametric Mapping. Clusters of low CMRGlu were observed bilaterally in the posterior cingulate cortex (PCC), in the precuneus, in the inferior parietal lobule and middle temporal gyrus of AD patients. In aMCI patients, reduced CMRGlu was found only in PCC. Areas of low CMRGlu in PCC were wider in AD compared to aMCI and extended to the precuneus, while low CMRGlu was found in the lateral parietal cortex in AD but not in aMCI patients. Individual subject pattern analysis revealed that 86% of AD patients had low CMRGlu in the PCC (including the precuneus in 71%), 71% in the temporal cortex, 64% in the parietal cortex and 35% in the frontal cortex. Among the aMCI patients, 56% had low CMRGlu in the PCC, 44% in the temporal cortex, 18% in the frontal cortex and none in the parietal cortex. This study demonstrates that both AD and aMCI patients have highly heterogeneous metabolic impairment. This potential of individual metabolic PET imaging in patients with AD and aMCI may allow timely identification of brain damage on individual basis and possibly help planning tailored early interventions. (orig.)

  19. Nitric oxide does not act as a mediator coupling cerebral blood flow to neural activity following somatosensory stimuli in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Kjaer, T; Jørgensen, M B;

    1993-01-01

    The possible role of nitric oxide (NO) on vibrissa-stimulated increase of regional cerebral cerebral blood flow (rCBF) and cerebral metabolic rate of glucose (rCMRglu) was investigated in conscious Wistar rats by using an inhibitor of NO synthase, NG-nitro-L-arginine (NOLAG) at a concentration of...

  20. Cerebral Metabolic Profiling of Hypothermic Circulatory Arrest with and Without Antegrade Selective Cerebral Perfusion: Evidence from Nontargeted Tissue Metabolomics in a Rabbit Model

    Institute of Scientific and Technical Information of China (English)

    Li-Hua Zou; Jin-Ping Liu; Hao Zhang; Shu-Bin Wu; Bing-Yang Ji

    2016-01-01

    Background:Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA).However,brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology.Methods:To clarify the metabolomics profiling of ASCP,12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group,n =6) and without (DHCA [D] group,n =6) ASCP according to the random number table.ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery.Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass.The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry.Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites,and then Student's t-test was applied to test for statistical significance between the two groups.Results:Metabolic profiling of brain was distinctive significantly between the two groups (Q2y =0.88 for partial least squares-DA model).In comparing to group D,62 definable metabolites were varied significantly after ASCP,which were mainly related to amino acid metabolism,carbohydrate metabolism,and lipid metabolism.Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway,subdued anaerobic metabolism,and oxidative stress.In addition,L-kynurenine (P =0.0019),5-methoxyindole-3-acetic acid (P =0.0499),and 5-hydroxyindole-3-acetic acid (P =0.0495) in tryptophan metabolism pathways were decreased,and citrulline (P =0.0158) in urea cycle was increased in group DA comparing to group D.Conclusions:The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP

  1. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    Energy Technology Data Exchange (ETDEWEB)

    Algotsson, L.; Messeter, K. (Department of Anaesthesiology, University Hospital, Lund (Sweden)); Rosen, I. (Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)); Holmin, T. (Department of Surgery, University Hospital, Lund (Sweden))

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo[sub 2]), and quantified electroencephalography (EEG) under two sets of conditions: (1) 1.7% end-tidal concentration of isoflurane in air/oxygen: (2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N[sub 2]O)/oxygen. The object was to study the effects of N[sub 2]O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N[sub 2]O in the anaesthetic gas mixture caused a 43% (P<0.05) increase in CBF during normocarbic conditions but no significant change during hypocapnia. CMRo[sub 2] was not significantly altered by N[sub 2]O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N[sub 2]O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au).

  2. Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria.

    Science.gov (United States)

    Villa, Roberto Federico; Ferrari, Federica; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio

    2016-08-25

    Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed. Antidepressants in vivo treatment modified the activities of selected enzymes of different mitochondria, leading to metabolic modifications in the energy metabolism of brain cortex: (a) the enhancement of cytochrome oxidase activity on somatic mitochondria; (b) the decrease of malate, succinate dehydrogenase and glutamate-pyruvate transaminase activities of synaptic mitochondria; (c) the selective effect of fluoxetine on enzymes related to glutamate metabolism. These results overcome the conflicting data so far obtained with antidepressants on brain energy metabolism, because the enzymatic analyses were made on mitochondria with diversified neuronal in vivo localization, i.e. on somatic and synaptic. This research is the first investigation on the pharmacodynamics of antidepressants studied at subcellular level, in the perspective of (i) assessing the role of energy metabolism of cerebral mitochondria in animal models of mood disorders, and (ii) highlighting new therapeutical strategies for antidepressants targeting brain bioenergetics.

  3. 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.

  4. 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

    DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase...... further increased the maximum specific growth rate to 0.069 h-1. Conclusions: In this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing...... 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....

  5. 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.

  6. 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...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03

  7. Selective and Efficient Elimination of Vibrio cholerae with a Chemical Modulator that Targets Glucose Metabolism

    Science.gov (United States)

    Oh, Young Taek; Kim, Hwa Young; Kim, Eun Jin; Go, Junhyeok; Hwang, Wontae; Kim, Hyoung Rae; Kim, Dong Wook; Yoon, Sang Sun

    2016-01-01

    Vibrio cholerae, a Gram-negative bacterium, is the causative agent of pandemic cholera. Previous studies have shown that the survival of the seventh pandemic El Tor biotype V. cholerae strain N16961 requires production of acetoin in a glucose-rich environment. The production of acetoin, a neutral fermentation end-product, allows V. cholerae to metabolize glucose without a pH drop, which is mediated by the production of organic acid. This finding suggests that inhibition of acetoin fermentation can result in V. cholerae elimination by causing a pH imbalance under glucose-rich conditions. Here, we developed a simple high-throughput screening method and identified an inducer of medium acidification (iMAC). Of 8364 compounds screened, we identified one chemical, 5-(4-chloro-2-nitrobenzoyl)-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione, that successfully killed glucose-metabolizing N16961 by inducing acidic stress. When N16961 was grown with abundant glucose in the presence of iMAC, acetoin production was completely suppressed and concomitant accumulation of lactate and acetate was observed. Using a beta-galactosidase activity assay with a single-copy palsD::lacZ reporter fusion, we show that that iMAC likely inhibits acetoin production at the transcriptional level. Thin-layer chromatography revealed that iMAC causes a significantly reduced accumulation of intracellular (p)ppGpp, a bacterial stringent response alarmone known to positively regulate acetoin production. In vivo bacterial colonization and fluid accumulation were also markedly decreased after iMAC treatment. Finally, we demonstrate iMAC-induced bacterial killing for 22 different V. cholerae strains belonging to diverse serotypes. Together, our results suggest that iMAC, acting as a metabolic modulator, has strong potential as a novel antibacterial agent for treatment against cholera. PMID:27900286

  8. 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.

  9. Sexual dimorphism in glucose and lipid metabolism during fasting, hypoglycemia and exercise

    Directory of Open Access Journals (Sweden)

    Maka S Hedrington

    2015-04-01

    Full Text Available Sexually dimorphic physiologic responses occur during fasting, hypoglycemia and exercise. The areas covered in this mini review include studies that have used isotopic tracer methods and/or euglycemic clamp studies to investigate substrate metabolism during the above common physiologic stress. Women have greater reliance on lipid metabolism during fasting, hypoglycemia and exercise while men exhibit preference of carbohydrate utilization. Plasma glucose concentrations were shown to be lower, while free fatty acids (FFA and lipolysis higher in women compared to men after fasting. Hypoglycemia resulted in significantly reduced epinephrine, norepinephrine, glucagon, growth hormone, pancreatic polypeptide and hepatic glucose production responses in females as compared to males. Sexual dimorphism during exercise was demonstrated by higher glycerol and FFA responses in women compared to men and higher carbohydrate oxidation rate in men. Mechanisms that can increase lipolytic rates in women include higher total fat mass, enhanced lipolytic sensitivity to epinephrine and increased activation of β adrenergic receptors.

  10. 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...... consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had...... increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non...

  11. Impact of expression of EMP enzymes on glucose metabolism in Zymomonas mobilis.

    Science.gov (United States)

    Chen, Rachel Ruizhen; Agrawal, Manoj; Mao, Zichao

    2013-06-01

    Zymomonas mobilis is the only known microorganism that utilizes the Entner-Doudoroff (ED) pathway anaerobically. In this work, we investigated whether the overexpression of a phosphofructokinase (PFK), the only missing Embden-Meyerhof-Parnas (EMP) pathway enzyme, could establish the pathway in this organism. Introduction of a pyrophosphate-dependent PFK, along with co-expression of homologous fructose-1,6-bisphosphate aldolase and triosephosphate isomerase, did not result in an EMP flux to any appreciable level. However, the metabolism of glucose was impacted significantly. Eight percent of glucose was metabolized to form a new metabolite, dihydroxyacetone. Reducing flux through the ED pathway by as much as 40 % through antisense of a key enzyme, ED aldolase, did not result in a fully functional EMP pathway, suggesting that the ED pathway, especially the lower arm, downstream from glyceraldehyde-3-phosphate, is very rigid, possibly due to redox balance.

  12. Prevalence of depression in individuals with impaired glucose metabolism or undiagnosed diabetes

    DEFF Research Database (Denmark)

    Nouwen, Arie; Nefs, Giesje; Caramlau, Isabela

    2011-01-01

    diagnosed type 2 diabetes (PDD) has not been the subject of a systematic review/meta-analysis. This study examined the prevalence of depression in IGM and UDD subjects relative to each other and to NGM and PDD subjects by reviewing the literature and conducting a meta-analysis of studies on this topic....... RESEARCH DESIGN AND METHODS: EMBASE and MEDLINE databases were searched for articles published up to May 2010. All studies that compared the prevalence of depression in subjects with IGM and UDD were included. Odds ratios (ORs) were calculated using fixed and random-effects models. RESULTS: The meta......OBJECTIVE: Meta-analyses have shown that the risk for depression is elevated in type 2 diabetes. Whether this risk in individuals with impaired glucose metabolism (IGM) or undiagnosed diabetes (UDD) is elevated relative to normal glucose metabolism (NGM) or decreased relative to previously...

  13. [Comparative characteristics of glucose metabolism in the liver of rats under acute alcohol and morphine intoxication].

    Science.gov (United States)

    Lelevich, S V

    2011-01-01

    The comparative analysis effect of acute alcohol and morphine intoxications on rats on hepatic glycolysis and pentose phosphate pathway was done. The dose-dependent inhibitory effect of ethanol on activity of limiting enzymes of these metabolic ways, as well as anaerobic reorientation of glucose metabolism was recognised with the increase of the dose of the intake alcohol. Morfine (10 mg/kg) activated enymes of glycolysis and pentose phosphate pathway, but in contrast to ethanol it did not influence these parameters at the dose 20 or 40 mg/kg.

  14. Abnormal Glucose Metabolism in Alzheimer’s Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches

    Science.gov (United States)

    Banerjee, Kalpita; Munshi, Soumyabrata; Frank, David E.; Gibson, Gary E.

    2015-01-01

    Diminished glucose metabolism accompanies many neurodegenerative diseases including Alzheimer’s disease. An understanding of the relation of these metabolic changes to the disease will enable development of novel therapeutic strategies. Following a metabolic challenge, cells generally conserve energy to preserve viability. This requires activation of many cellular repair/regenerative processes such as mitophagy/autophagy and fusion/fission. These responses may diminish cell function in the long term. Prolonged fission induces mitophagy/autophagy which promotes repair but if prolonged progresses to mitochondrial degradation. Abnormal glucose metabolism alters protein signaling including the release of proteins from the mitochondria or migration of proteins from the cytosol to the mitochondria or nucleus. This overview provides an insight into the different mechanisms of autophagy/mitophagy and mitochondrial dynamics in response to the diminished metabolism that occurs with diseases, especially neurodegenerative diseases such as Alzheimer's disease. The review discusses multiple aspects of mitochondrial responses including different signaling proteins and pathways of mitophagy and mitochondrial biogenesis. Improving cellular bioenergetics and mitochondrial dynamics will alter protein signaling and improve cellular/mitochondrial repair and regeneration. An understanding of these changes will suggest new therapeutic strategies. PMID:26077923

  15. 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.

  16. 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.

  17. Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach

    Energy Technology Data Exchange (ETDEWEB)

    Mazzetti, Marta Blanca; Taira, Maria Cristina; Lelli, Sandra Marcela; Viale, Leonor Carmen San Martin de [Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428BGA, Ciudad Autonoma Buenos Aires (Argentina); Dascal, Eduardo; Basabe, Juan Carlos [Centro de Investigaciones Endocrinologicas (CEDIE). Hospital de Ninos, Dr. Ricardo Gutierrez, C1425EDF, Ciudad Autonoma Buenos Aires (Argentina)

    2004-01-01

    Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative

  18. 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.

  19. 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.

  20. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role

    OpenAIRE

    Hage, Mirella P.; Al-Badri, Marwa R.; Azar, Sami T.

    2014-01-01

    Hydroxychloroquine (HCQ), a commonly used antimalarial drug in rheumatic diseases, has shown favorable metabolic effects on both glucose control and lipid profiles. We describe a case of a young woman with type 1 diabetes whose glycemic control was optimized with the introduction of HCQ as a treatment for her Sjogren syndrome in addition to a subtle yet measurable improvement in her lipid profile. An increasing body of evidence supports the beneficial impacts of HCQ in various ancillary condi...

  1. Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study

    OpenAIRE

    Strand, Linn Beate; Carnethon, Mercedes; Biggs, Mary Lou; Djoussé, Luc; Kaplan, Robert C.; David S Siscovick; Robbins, John A.; Redline, Susan; Patel, Sanjay R.; Janszky, Imre; Mukamal, Kenneth J.

    2015-01-01

    OBJECTIVE We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 19...

  2. Nosocomial pneumonia caused by a glucose-metabolizing strain of Neisseria cinerea.

    OpenAIRE

    Boyce, J M; Taylor, M R; Mitchell, E B; Knapp, J S

    1985-01-01

    We describe what appears to be the first reported case of nosocomial pneumonia caused by Neisseria cinerea. The isolate metabolized glucose when tested in BACTEC Neisseria Differentiation Kits (Johnston Laboratories), but did not produce detectable acid in cystine-Trypticase (BBL Microbiology Systems) agar medium or in modified oxidation-fermentation medium. Clinical laboratories that rely on the BACTEC method for differentiation of pathogenic neisseriae should be aware of the fact that N. ci...

  3. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Hiroshi [National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan). National Center Hospital for Mental, Nervous, and Muscular Disorders

    2001-04-01

    In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOE{epsilon}4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the {epsilon}4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single {epsilon}4 allele. On the contrary the relation of {epsilon}4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection

  4. 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

  5. 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.

  6. Olanzapine-induced changes in glucose metabolism are independent of the melanin-concentrating hormone system.

    Science.gov (United States)

    Girault, Elodie M; Toonen, Pim W; Eggels, Leslie; Foppen, Ewout; Ackermans, Mariëtte T; la Fleur, Susanne E; Fliers, Eric; Kalsbeek, Andries

    2013-11-01

    Atypical antipsychotic drugs such as Olanzapine (Ola) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side-effects are currently unknown. Chagnon et al. showed that the common allele rs7973796 of the prepro-melanin-concentrating hormone (PMCH) gene is associated with a greater body mass index in Ola-treated schizophrenic patients. As PMCH encodes for the orexigenic neuropeptide melanin-concentrating hormone (MCH), it was hypothesized that MCH is involved in Ola-induced metabolic changes. We have recently reported that the intragastric infusion of Ola results in hyperglycaemia and insulin resistance in male rats. In order to test in vivo the possible involvement of the PMCH gene in the pathogenesis of Ola side-effects, we administered Ola intragastrically in wild-type (WT) and PMCH knock-out (KO) rats. Our results show that glucose and corticosterone levels, as well as endogenous glucose production, are elevated by the infusion of Ola in both WT and KO animals. Thus, the lack of MCH does not seem to affect the acute effects of Ola on glucose metabolism. On the other hand, these effects might be obliterated by compensatory changes in other hypothalamic systems. In addition, possible modulatory effects of the MCH KO on the long term effects of Ola, i.e. increased adiposity, body weight gain, have not been investigated yet.

  7. 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.

  8. Genetic enhancement of microsomal epoxide hydrolase improves metabolic detoxification but impairs cerebral blood flow regulation.

    Science.gov (United States)

    Marowsky, Anne; Haenel, Karen; Bockamp, Ernesto; Heck, Rosario; Rutishauser, Sibylle; Mule, Nandkishor; Kindler, Diana; Rudin, Markus; Arand, Michael

    2016-12-01

    Microsomal epoxide hydrolase (mEH) is a detoxifying enzyme for xenobiotic compounds. Enzymatic activity of mEH can be greatly increased by a point mutation, leading to an E404D amino acid exchange in its catalytic triad. Surprisingly, this variant is not found in any vertebrate species, despite the obvious advantage of accelerated detoxification. We hypothesized that this evolutionary avoidance is due to the fact that the mEH plays a dualistic role in detoxification and control of endogenous vascular signaling molecules. To test this, we generated mEH E404D mice and assessed them for detoxification capacity and vascular dynamics. In liver microsomes from these mice, turnover of the xenobiotic compound phenanthrene-9,10-oxide was four times faster compared to WT liver microsomes, confirming accelerated detoxification. mEH E404D animals also showed faster metabolization of a specific class of endogenous eicosanoids, arachidonic acid-derived epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). Significantly higher DHETs/EETs ratios were found in mEH E404D liver, urine, plasma, brain and cerebral endothelial cells compared to WT controls, suggesting a broad impact of the mEH mutant on endogenous EETs metabolism. Because EETs are strong vasodilators in cerebral vasculature, hemodynamics were assessed in mEH E404D and WT cerebral cortex and hippocampus using cerebral blood volume (CBV)-based functional magnetic resonance imaging (fMRI). Basal CBV0 levels were similar between mEH E404D and control mice in both brain areas. But vascular reactivity and vasodilation in response to the vasodilatory drug acetazolamide were reduced in mEH E404D forebrain compared to WT controls by factor 3 and 2.6, respectively. These results demonstrate a critical role for mEH E404D in vasodynamics and suggest that deregulation of endogenous signaling pathways is the undesirable gain of function associated with the E404D variant.

  9. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.

    Science.gov (United States)

    Seyfried, T N; Sanderson, T M; El-Abbadi, M M; McGowan, R; Mukherjee, P

    2003-10-06

    Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KD restricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, beta-hydroxybutyrate (beta-OHB), and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SD-UR and KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate that plasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories. Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression. Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reduce stromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies.

  10. Evaluation of hepatic glucose metabolism via gluconeogenesis and glycogenolysis after oral administration of insulin nanoparticles.

    Science.gov (United States)

    Woitiski, Camile B; Neufeld, Ronald J; Soares, Ana F; Figueiredo, Isabel V; Veiga, Francisco J; Carvalho, Rui A

    2012-12-01

    Nanoparticles were designed to promote insulin intestinal absorption via the oral route, to increase portal insulin levels to better mimic the physiological pathway, providing enhanced glucose control through glycogenolysis and gluconeogenesis. Nanoparticles were formulated with insulin encapsulated in the core material consisting of alginate and dextran sulfate, associated with poloxamer and subsequently coated with chitosan then albumin. A spherical and slightly rough core was observed in electron micrographs with the appearance of a concentration gradient of the polysaccharide structure toward the periphery of the nanoparticle. Atomic force microscopy showed that the fully formed nanoparticles are about 200 nm in diameter with smooth and spherical morphology. Histopathological analysis of organs and tissues of diabetic rats dosed daily for 15 days with insulin nanoparticles was used to evaluate toxicological issues. No morphological or pathological alterations were observed in rat liver, spleen, pancreas, kidney or intestinal sections. Following, the effect of nanoencapsulated insulin on inhibiting hepatic gluconeogenesis was evaluated after a single insulin administration and oral glucose tolerance test, which represents a significant metabolic challenge to the liver. Alterations in the hepatic glucose metabolism of fasted streptozotocin-diabetic rats were determined by the percent contribution of glycogenolysis and gluconeogenesis, measured by using metabolic tracers, however similar gluconeogenesis contribution to the hepatic metabolism was observed between diabetic rats receiving nanoencapsulated insulin or insulin solution. The metabolic results may be explained by the inability of a single dose in shifting the gluconeogenesis/glycogenolysis contributions, sampling time, fasting period or by influence of the kidney enzymes and impairment in insulin signaling observed in stz-diabetic rats.

  11. Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study.

    Directory of Open Access Journals (Sweden)

    Jennifer Kriebel

    Full Text Available Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10(-5 and 0.047. In addition, DNA methylation at cg06500161 (annotated to ABCG1 was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10(-5 and 3.0x10(-3. Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI (B-H-adjusted p-values = 0.047. Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1 was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10(-9. Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and

  12. Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study.

    Science.gov (United States)

    Kriebel, Jennifer; Herder, Christian; Rathmann, Wolfgang; Wahl, Simone; Kunze, Sonja; Molnos, Sophie; Volkova, Nadezda; Schramm, Katharina; Carstensen-Kirberg, Maren; Waldenberger, Melanie; Gieger, Christian; Peters, Annette; Illig, Thomas; Prokisch, Holger; Roden, Michael; Grallert, Harald

    2016-01-01

    Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10(-5) and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10(-5) and 3.0x10(-3)). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10(-9)). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes

  13. 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

  14. 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

  15. Cerebral metabolic changes in neurologically presymptomatic patients undergoing haemodialysis: in vivo proton MR spectroscopic findings

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Ming-Lun; Chiang, I. Chan [Kaohsiung Medical University Hospital, Department of Medical Imaging (China); Li, Chun-Wei [Kaohsiung Medical University, Department of Medical Imaging and Radiological Sciences, College of Health Science (China); Chang, Jer-Ming [Kaohsiung Medical University, Department of Internal Medicine, Kaohsiung Hsiao-Kang Municipal Hospital (China); Kaohsiung Medical University, Department of Nephrology, School of Medicine, College of Medicine (China); Ko, Chih-Hung [Kaohsiung Medical University, Department of Psychiatry, School of Medicine, College of Medicine (China); Kaohsiung Medical University Hospital, Department of Psychiatry (China); Chuang, Hung-Yi [Kaohsiung Medical University, Faculty of Public Health, College of Health Science (China); Kaohsiung Medical University Hospital, Department of Environmental and Occupational Medicine (China); Sheu, Reu-Sheng [Kaohsiung Medical University, Department of Radiology, Kaohsiung Municipal Hsiao-Kang Hospital (China); Kaohsiung Medical University, Department of Radiology, Faculty of Medicine, College of Medicine (China); Lee, Chen-Chang [Kaohsiung Medical University, Department of Medical Imaging and Radiological Sciences, College of Health Science (China); Kaohsiung Medical Centre, Department of Radiology, Chang Gung Memorial Hospital (China); Hsieh, Tsyh-Jyi [Kaohsiung Medical University Hospital, Department of Medical Imaging (China); Kaohsiung Medical University, Department of Radiology, Faculty of Medicine, College of Medicine (China); Kaohsiung Municipal Ta-Tung Hospital, Department of Medical Imaging (China)

    2010-06-15

    To prospectively investigate and detect early cerebral metabolic changes in patients with end-stage renal disease (ESRD) by using in vivo proton MR spectroscopy (MRS). We enrolled 32 patients with ESRD and 32 healthy controls between the ages of 26 and 50 years. Short echo time single-voxel proton MRS was acquired from volumes of interest (VOIs) located in the frontal grey and white matter, temporal white matter and basal ganglia. The choline/phospatidylcholine (Cho), myo-inositol (mI), N-acetylaspartate (NAA) and total creatine (tCr) peaks were measured and the metabolic ratios with respect to tCr were calculated. In the ESRD group, significant elevations of the Cho/tCr and mI/tCr ratios were observed for the frontal grey matter, frontal white matter, temporal white matter and basal ganglia as compared with controls. There was no significant difference in the NAA/tCr ratios at all VOIs between the ESRD patients and the healthy controls. Proton MRS is a useful and non-invasive imaging tool for the detection of early cerebral metabolic changes in neurologically presymptomatic ESRD patients. (orig.)

  16. Association between fatigue and failure to preserve cerebral energy turnover during prolonged exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Møller, Kirsten; Pedersen, Bente Klarlund

    2003-01-01

    AIM: This study evaluated if the fatigue and apathy arising during exercise with hypoglycaemia could relate to a lowering of the cerebral metabolic rates of glucose and oxygen. METHODS AND RESULTS: Six males completed 3 h of cycling with or without glucose supplementation in random order. Cerebral...... was accompanied by a lowering of the cerebral metabolic rate of oxygen from 1.84 +/- 0.19 mmol g(-1) min(-)1 during exercise with glucose supplementation to 1.60 +/- 0.16 mmol g(-1) min(-1) during hypoglycaemia (P

  17. 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

  18. Fast dynamic response of the fermentative metabolism of Escherichia coli to aerobic and anaerobic glucose pulses.

    Science.gov (United States)

    Lara, Alvaro R; Taymaz-Nikerel, Hilal; Mashego, Mlawule R; van Gulik, Walter M; Heijnen, Joseph J; Ramírez, Octavio T; van Winden, Wouter A

    2009-12-15

    The response of Escherichia coli cells to transient exposure (step increase) in substrate concentration and anaerobiosis leading to mixed-acid fermentation metabolism was studied in a two-compartment bioreactor system consisting of a stirred tank reactor (STR) connected to a mini-plug-flow reactor (PFR: BioScope, 3.5 mL volume). Such a system can mimic the situation often encountered in large-scale, fed-batch bioreactors. The STR represented the zones of a large-scale bioreactor that are far from the point of substrate addition and that can be considered as glucose limited, whereas the PFR simulated the region close to the point of substrate addition, where glucose concentration is much higher than in the rest of the bioreactor. In addition, oxygen-poor and glucose-rich regions can occur in large-scale bioreactors. The response of E. coli to these large-scale conditions was simulated by continuously pumping E. coli cells from a well stirred, glucose limited, aerated chemostat (D = 0.1 h(-1)) into the mini-PFR. A glucose pulse was added at the entrance of the PFR. In the PFR, a total of 11 samples were taken in a time frame of 92 s. In one case aerobicity in the PFR was maintained in order to evaluate the effects of glucose overflow independently of oxygen limitation. Accumulation of acetate and formate was detected after E. coli cells had been exposed for only 2 s to the glucose-rich (aerobic) region in the PFR. In the other case, the glucose pulse was also combined with anaerobiosis in the PFR. Glucose overflow combined with anaerobiosis caused the accumulation of formate, acetate, lactate, ethanol, and succinate, which were also detected as soon as 2 s after of exposure of E. coli cells to the glucose and O(2) gradients. This approach (STR-mini-PFR) is useful for a better understanding of the fast dynamic phenomena occurring in large-scale bioreactors and for the design of modified strains with an improved behavior under large-scale conditions.

  19. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse, human glioblastomas in the mouse brain in vivo

    Science.gov (United States)

    Marin-Valencia, Isaac; Yang, Chendong; Mashimo, Tomoyuki; Cho, Steve; Baek, Hyeonman; Yang, Xiao-Li; Rajagopalan, Kartik N.; Maddie, Melissa; Vemireddy, Vamsidhara; Zhao, Zhenze; Cai, Ling; Good, Levi; Tu, Benjamin P.; Hatanpaa, Kimmo J.; Mickey, Bruce E.; Matés, José M.; Pascual, Juan M.; Maher, Elizabeth A.; Malloy, Craig R.; DeBerardinis, Ralph J.; Bachoo, Robert M.

    2012-01-01

    SUMMARY Dysregulated metabolism is a hallmark of cancer cell lines, but little is known about the fate of glucose and other nutrients in tumors growing in their native microenvironment. To study tumor metabolism in vivo, we used an orthotopic mouse model of primary human glioblastoma (GBM). We infused 13C-labeled nutrients into mice bearing three independent GBM lines, each with a distinct set of mutations. All three lines displayed glycolysis, as expected for aggressive tumors. They also displayed unexpected metabolic complexity, oxidizing glucose via pyruvate dehydrogenase and the citric acid cycle, and using glucose to supply anaplerosis and other biosynthetic activities. Comparing the tumors to surrounding brain revealed obvious metabolic differences, notably the accumulation of a large glutamine pool within the tumors. Many of these same activities were conserved in cells cultured ex vivo from the tumors. Thus GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo. PMID:22682223

  20. 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.

  1. Complex Patterns of Metabolic and Ca2+ Entrainment in Pancreatic Islets by Oscillatory Glucose

    OpenAIRE

    Pedersen, Morten Gram; Mosekilde, Erik; Polonsky, Kenneth S.; Luciani, Dan Seriano

    2013-01-01

    Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca2+in pancreatic islets. Periodic variations in glucose can entrain islet Ca2+ and insulin secretion, possibly promoting interislet synchronization. Here, we used fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) in...

  2. 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.

  3. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism

    DEFF Research Database (Denmark)

    Galindo, C; Larsen, Mogens; Ouellet, D R

    2015-01-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate...

  4. Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models

    Institute of Scientific and Technical Information of China (English)

    Yi Zhang; Chun-Sheng Li; Cai-Jun Wu; Jun Yang; Chen-Chen Hang

    2015-01-01

    Background:Morbidity and mortality after resuscitation largely depend on the recovery of brain function.Ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are the two most prevalent causes of sudden cardiac death.Up to now,most studies have focused on VFCA.However,results from the two models have been largely variable.So,it is necessary to characterize the features of postresuscitation cerebral metabolism of both models.Methods:Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups:18 for VFCA group,ACA group,respectively,and other 8 for sham-operated group (SHAM).VFCA was induced by programmed electric stimulation,andACA was induced by endotracheal tube clamping.After 8 min without treatment,standard cardiopulmonary resuscitation (CPR) was initiated.Following neurological deficit scores (NDS) were evaluated at 24 h after achievement of spontaneous circulation,cerebral metabolism showed as the maximum standardized uptake value (SUVmax) was measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography.Levels of serum markers of brain injury,neuron specific enolase (NSE),and S100β were quantified with an enzyme-linked immunosorbent assay.Results:Compared with VFCA group,fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs.94.4%,P < 0.01) and survived 24-h after resuscitation (38.9% vs.77.8%,P < 0.01) with worse neurological outcome (NDS:244.3 ± 15.3 vs.168.8 ± 9.71,P < 0.01).The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs.4.5 ± 1.1 min,P < 0.01).Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01).Higher serum biomarkers of brain damage (NSE,S100β) were found inACA than VFCA after resuscitation (P < 0.01).Conclusions:Compared with VFCA,ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse neurological outcome.

  5. Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2015-01-01

    Full Text Available Background: Morbidity and mortality after resuscitation largely depend on the recovery of brain function. Ventricular fibrillation cardiac arrest (VFCA and asphyxial cardiac arrest (ACA are the two most prevalent causes of sudden cardiac death. Up to now, most studies have focused on VFCA. However, results from the two models have been largely variable. So, it is necessary to characterize the features of postresuscitation cerebral metabolism of both models. Methods: Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: 18 for VFCA group, ACA group, respectively, and other 8 for sham-operated group (SHAM. VFCA was induced by programmed electric stimulation, and ACA was induced by endotracheal tube clamping. After 8 min without treatment, standard cardiopulmonary resuscitation (CPR was initiated. Following neurological deficit scores (NDS were evaluated at 24 h after achievement of spontaneous circulation, cerebral metabolism showed as the maximum standardized uptake value (SUVmax was measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Levels of serum markers of brain injury, neuron specific enolase (NSE, and S100β were quantified with an enzyme-linked immunosorbent assay. Results: Compared with VFCA group, fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs. 94.4%, P < 0.01 and survived 24-h after resuscitation (38.9% vs. 77.8%, P < 0.01 with worse neurological outcome (NDS: 244.3 ± 15.3 vs. 168.8 ± 9.71, P < 0.01. The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs. 4.5 ± 1.1 min, P < 0.01. Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01. Higher serum biomarkers of brain damage (NSE, S100β were found in ACA than VFCA after resuscitation (P < 0.01. Conclusions: Compared with VFCA, ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse

  6. 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

  7. Effects of sleep disruption and high fat intake on glucose metabolism in mice.

    Science.gov (United States)

    Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R

    2016-06-01

    Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this

  8. 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.

  9. Investigation of (/sup 18/F)2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-12-01

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man.

  10. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role.

    Science.gov (United States)

    Hage, Mirella P; Al-Badri, Marwa R; Azar, Sami T

    2014-08-01

    Hydroxychloroquine (HCQ), a commonly used antimalarial drug in rheumatic diseases, has shown favorable metabolic effects on both glucose control and lipid profiles. We describe a case of a young woman with type 1 diabetes whose glycemic control was optimized with the introduction of HCQ as a treatment for her Sjogren syndrome in addition to a subtle yet measurable improvement in her lipid profile. An increasing body of evidence supports the beneficial impacts of HCQ in various ancillary conditions, including diabetes mellitus and dyslipidemia. However, mechanisms of action responsible for these effects remain ill-defined and may include alterations in insulin metabolism and signaling through cellular receptors. These favorable metabolic effects of HCQ and further understanding of underlying mechanisms may provide an additional rational for its use in rheumatic diseases, conditions associated with an elevated cardiovascular risk.

  11. 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.

  12. Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO/sub 2/

    Energy Technology Data Exchange (ETDEWEB)

    Murkin, J.M.; Farrar, J.K.; Tweed, W.A.; McKenzie, F.N.; Guiraudon, G.

    1987-09-01

    Measurement of /sup 133/Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO/sub 2/ at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO/sub 2/ of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.

  13. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Richard J. Naftalin

    2016-04-01

    Full Text Available A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD, non-alcoholic steatohepatitis, (NASH and type 2 diabetes mellitus, (T2DM demonstrates how when glucagon-like peptide-1, (GLP-1 is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU. When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic

  14. Plasma myeloperoxidase is inversely associated with endothelium-dependent vasodilation in elderly subjects with abnormal glucose metabolism.

    Science.gov (United States)

    van der Zwan, Leonard P; Teerlink, Tom; Dekker, Jacqueline M; Henry, Ronald M A; Stehouwer, Coen D A; Jakobs, Cornelis; Heine, Robert J; Scheffer, Peter G

    2010-12-01

    Myeloperoxidase (MPO), a biomarker related to inflammation, oxidative stress, and nitric oxide scavenging, has been shown to impair endothelium-dependent vasodilation. Because elevated hydrogen peroxide concentrations in diabetic vessels may enhance MPO activity, we hypothesized that a stronger association of MPO with flow-mediated dilation (FMD) may be found in subjects with abnormal glucose metabolism. Myeloperoxidase concentrations were measured in EDTA plasma samples from participants of a population-based cohort study, including 230 subjects with normal glucose metabolism and 386 with abnormal glucose metabolism. Vascular function was expressed as FMD and nitroglycerin-mediated dilation of the brachial artery. In subjects with abnormal glucose metabolism, MPO was negatively associated with FMD (-20.9 [95% confidence interval {CI}, -41.7 to -0.2] -μm change in FMD per SD increment of MPO). This association remained significant after adjustment for nitroglycerin-mediated dilation (-31.1 [95% CI, -50.0 to -12.3]) and was not attenuated after further adjustment for established risk factors. In subjects with normal glucose metabolism, MPO was not significantly associated with FMD (2.0 [95% CI, -16.0 to 20.0]). In conclusion, in subjects with abnormal glucose metabolism, plasma levels of MPO are inversely associated with endothelium-dependent vasodilation, possibly reflecting enhancement of MPO activity by vascular oxidative stress.

  15. Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry.

    Science.gov (United States)

    Sheng, Zhenyu; Santiago, Ammy M; Thomas, Mark P; Routh, Vanessa H

    2014-09-01

    Lateral hypothalamic area (LHA) orexin neurons modulate reward-based feeding by activating ventral tegmental area (VTA) dopamine (DA) neurons. We hypothesize that signals of peripheral energy status influence reward-based feeding by modulating the glucose sensitivity of LHA orexin glucose-inhibited (GI) neurons. This hypothesis was tested using electrophysiological recordings of LHA orexin-GI neurons in brain slices from 4 to 6week old male mice whose orexin neurons express green fluorescent protein (GFP) or putative VTA-DA neurons from C57Bl/6 mice. Low glucose directly activated ~60% of LHA orexin-GFP neurons in both whole cell and cell attached recordings. Leptin indirectly reduced and ghrelin directly enhanced the activation of LHA orexin-GI neurons by glucose decreases from 2.5 to 0.1mM by 53±12% (n=16, PFasting increased activation of LHA orexin-GI neurons by decreased glucose, as would be predicted by these hormonal effects. We also evaluated putative VTA-DA neurons in a novel horizontal slice preparation containing the LHA and VTA. Decreased glucose increased the frequency of spontaneous excitatory post-synaptic currents (sEPSCs; 125 ± 40%, n=9, P<0.05) and action potentials (n=9; P<0.05) in 45% (9/20) of VTA DA neurons. sEPSCs were completely blocked by AMPA and NMDA glutamate receptor antagonists (CNQX 20 μM, n=4; APV 20μM, n=4; respectively), demonstrating that these sEPSCs were mediated by glutamatergic transmission onto VTA DA neurons. Orexin-1 but not 2 receptor antagonism with SB334867 (10μM; n=9) and TCS-OX2-29 (2μM; n=5), respectively, blocks the effects of decreased glucose on VTA DA neurons. Thus, decreased glucose increases orexin-dependent excitatory glutamate neurotransmission onto VTA DA neurons. These data suggest that the glucose sensitivity of LHA orexin-GI neurons links metabolic state and reward-based feeding.

  16. Time courses of behavioral and regional cerebral metabolic responses to different doses of meta-chlorophenylpiperazine in awake rats.

    Science.gov (United States)

    Freo, U; Soncrant, T T; Ricchieri, G L; Wozniak, K M; Larson, D M; Rapoport, S I

    1990-03-19

    The time course and relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) and of motor behavior were measured in awake male adult Fischer-344 rats after administration of meta-chlorophenylpiperazine (MCPP), a serotonin-1B receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 71 brain regions at 5, 15, 30 and 60 min after administration of MCPP 2.5 mg/kg i.p., and at 15 min after MCPP 25 and 40 mg/kg. The time course of performance on a rotating rod was measured periodically for 60 min after MCPP 2.5 mg/kg, a dose which impaired locomotion and reduced rCMRglc maximally at 15-30 min after its administration. At 15 min, rCMRglc declined significantly in 28 (40%) of the areas studied (mean decline 16%). Most regions affected were telencephalic or diencephalic, corresponding to the projection areas of serotonergic fibers arising from the raphe nuclei. After higher doses of MCPP, a behavioral serotonin syndrome was observed with both rCMRglc increases and decreases (25 mg/kg) or only rCMRglc increases (40 mg/kg). Whereas behavioral and metabolic activation induced by high doses of MCPP may result from stimulation at postsynaptic serotonin receptors, rCMRglc reductions and hypomotility produced by MCPP 2.5 mg/kg resemble the effects of serotonin receptor antagonists and suggest that, at this low dose, MCPP acts at modulatory serotonin autoreceptors to reduce endogenous serotonin release.

  17. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

    Science.gov (United States)

    Venkat, Poornima; Chopp, Michael; Chen, Jieli

    2016-06-30

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

  18. The Role of Glucose Metabolism on Porcine Oocyte Cytoplasmic Maturation and Its Possible Mechanisms

    Science.gov (United States)

    Kwon, Jeong-Woo; Jin, Yong-Xun; Park, Shun-Ha; Wang, Hai-Yang; Sun, Tian-Yi; Zhang, Jia-Bao; Kim, Nam-Hyung

    2016-01-01

    In the present study, we investigated the potential role of glucose and pyruvate in the cytoplasmic maturation of porcine oocytes by investigating the effect of glucose and/or pyruvate supplementation, in the presence or absence of 10% porcine follicular fluid (PFF), on meiotic maturation and subsequent embryo development. In the absence of 10% PFF, without exogenous addition of glucose and pyruvate, the medium seemed unable to support maturation. In the presence of 10% PFF, the addition of 5.6 mM glucose and/or 2 mM pyruvate during in vitro maturation of cumulus enclosed oocytes increased MII oocyte and blastocyst rates. In contrast, oocytes denuded of cumulus cells were not able to take full advantage of the glucose in the medium, as only pyruvate was able to increase the MII rate and the subsequent early embryo developmental ability. Treatment of cumulus enclosed oocytes undergoing maturation with 200 μM dehydroepiandrosterone (DHEA), a pentose phosphate pathway inhibitor, or 2 μM iodoacetate (IA), a glycolysis inhibitor, significantly reduced GHS, intra-oocyte ATP, maternal gene expression, and MPF activity levels. DHEA was also able to increase ROS and reduce the levels of NADPH. Moreover, blastocysts of the DHEA- or IA-treated groups presented higher apoptosis rates and markedly lower cell proliferation cell rates than those of the non-treated group. In conclusion, our results suggest that oocytes maturing in the presence of 10% PFF can make full use of energy sources through glucose metabolism only when they are accompanied by cumulus cells, and that pentose phosphate pathway (PPP) and glycolysis promote porcine oocyte cytoplasmic maturation by supplying energy, regulating maternal gene expression, and controlling MPF activity. PMID:27997591

  19. Acute effects of concentric and eccentric exercise on glucose metabolism and interleukin-6 concentration in healthy males.

    Science.gov (United States)

    Philippe, M; Krüsmann, P J; Mersa, L; Eder, E M; Gatterer, H; Melmer, A; Ebenbichler, C; Burtscher, M

    2016-06-01

    Acute muscle-damaging eccentric exercise (EE) negatively affects glucose metabolism. On the other hand, long-term eccentric endurance exercise seems to result in equal or superior positive effects on glucose metabolism compared to concentric endurance exercise. However, it is not known if acute non-muscle-damaging EE will have the same positive effects on glucose metabolism as acute concentric exercise (CE). Interleukin-6 (IL-6) released from the exercising muscles may be involved in the acute adaptations of glucose metabolism after CE and non-muscle-damaging EE. The aim of this study was to assess acute effects of uphill walking (CE) and non-muscle-damaging downhill walking (EE) on glucose metabolism and IL-6 secretion. Seven sedentary non-smoking, healthy males participated in a crossover trial consisting of a 1 h uphill (CE) and a 1 h downhill (EE) walking block on a treadmill. Venous blood samples were drawn before (pre), directly after (acute) and 24 h after (post) exercise. An oral glucose tolerance test (OGTT) was performed before and 24 h after exercise. Glucose tolerance after 1 and 2 hours significantly improved 24 hours after CE (-10.12±3.22%: P=0.039; -13.40±8.24%: P=0.028). After EE only the 1-hour value was improved (-5.03±5.48%: P=0.043). Acute IL-6 concentration rose significantly after CE but not after EE. We conclude that both a single bout of CE and a single bout of non-muscle-damaging EE elicit positive changes in glucose tolerance even in young, healthy subjects. Our experiment indicates that the overall metabolic cost is a major trigger for acute adaptations of glucose tolerance after exercise, but only the IL-6 production during EE was closely related to changes in glycaemic control.

  20. Vitamin C inhibits leptin secretion and some glucose/lipid metabolic pathways in primary rat adipocytes.

    Science.gov (United States)

    Garcia-Diaz, D F; Campion, J; Milagro, F I; Boque, N; Moreno-Aliaga, M J; Martinez, J A

    2010-07-01

    Antioxidant-based treatments are emerging as an interesting approach to possibly counteract obesity fat accumulation complications, since this is accompanied by an increased systemic oxidative stress. The aim of this study was to analyze specific metabolic effects of vitamin C (VC) on epididymal primary rat adipocytes. Cells were isolated and incubated for 72 h in culture medium, in the absence or presence of 1.6 nM insulin, within a range of VC concentrations (5-1000 microM). Glucose- and lipid-related variables as well as the secretion/expression patterns of several obesity-related genes were assessed. It was observed that VC dose dependently inhibited glucose uptake and lactate production, and also reduced glycerol release in both control and insulin-treated cells. Also, VC caused a dramatic concentration-dependent fall in leptin secretion especially in insulin-stimulated cells. In addition, VC (200 microM) induced Cdkn1a and Casp8, partially inhibited Irs3, and together with insulin drastically reduced Gpdh (listed as Gpd1 in the MGI database) gene expressions. Finally, VC and insulin down-regulatory effects were observed on extracellular and intracellular reactive oxygen species production respectively. In summary, this experimental assay describes a specific effect of VC in isolated rat adipocytes on glucose and fat metabolism, and on the secretion/expression of important obesity-related proteins.

  1. Anorexia and Impaired Glucose Metabolism in Mice With Hypothalamic Ablation of Glut4 Neurons

    Science.gov (United States)

    Ren, Hongxia; Lu, Taylor Y.; McGraw, Timothy E.

    2015-01-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin–mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron–ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism. PMID:25187366

  2. Effect of phenolic acids on glucose and organic acid metabolism by lactic acid bacteria from wine.

    Science.gov (United States)

    Campos, Francisco M; Figueiredo, Ana R; Hogg, Tim A; Couto, José A

    2009-06-01

    The influence of phenolic (p-coumaric, caffeic, ferulic, gallic and protocatechuic) acids on glucose and organic acid metabolism by two strains of wine lactic acid bacteria (Oenococcus oeni VF and Lactobacillus hilgardii 5) was investigated. Cultures were grown in modified MRS medium supplemented with different phenolic acids. Cellular growth was monitored and metabolite concentrations were determined by HPLC-RI. Despite the strong inhibitory effect of most tested phenolic acids on the growth of O. oeni VF, the malolactic activity of this strain was not considerably affected by these compounds. While less affected in its growth, the capacity of L. hilgardii 5 to degrade malic acid was clearly diminished. Except for gallic acid, the addition of phenolic acids delayed the metabolism of glucose and citric acid in both strains tested. It was also found that the presence of hydroxycinnamic acids (p-coumaric, caffeic and ferulic) increased the yield of lactic and acetic acid production from glucose by O. oeni VF and not by L. hilgardii 5. The results show that important oenological characteristics of wine lactic acid bacteria, such as the malolactic activity and the production of volatile organic acids, may be differently affected by the presence of phenolic acids, depending on the bacterial species or strain.

  3. Inflammation in metabolic syndrome and type 2 diabetes: Impact of dietary glucose.

    Science.gov (United States)

    Kempf, Kerstin; Rose, Bettina; Herder, Christian; Kleophas, Ursula; Martin, Stephan; Kolb, Hubert

    2006-11-01

    Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose-induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.

  4. Diacylglycerol kinase ϵ deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice.

    Science.gov (United States)

    Mannerås-Holm, Louise; Schönke, Milena; Brozinick, Joseph T; Vetterli, Laurène; Bui, Hai-Hoang; Sanders, Philip; Nascimento, Emmani B M; Björnholm, Marie; Chibalin, Alexander V; Zierath, Juleen R

    2017-02-28

    Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of DAG into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKε in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKε deficient (KO) and wild-type mice. Lipidomic analysis revealed elevated unsaturated and saturated DAG species in skeletal muscle of DGKε KO mice, which was paradoxically associated with increased glucose tolerance. While skeletal muscle insulin sensitivity was unaltered, whole body respiratory exchange ratio was reduced, and abundance of mitochondrial markers was increased, indicating a greater reliance on fat oxidation and intracellular lipid metabolism in DGKε KO mice. Thus, the increased intracellular lipids in skeletal muscle from DGKε KO mice may undergo rapid turnover due to increased mitochondrial function and lipid oxidation, rather than storage, which in turn may preserve insulin sensitivity. In conclusion, DGKε plays a role in glucose and energy homeostasis by modulating lipid metabolism in skeletal muscle.

  5. Anorexia and impaired glucose metabolism in mice with hypothalamic ablation of Glut4 neurons.

    Science.gov (United States)

    Ren, Hongxia; Lu, Taylor Y; McGraw, Timothy E; Accili, Domenico

    2015-02-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin-mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron-ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism.

  6. Comprehensive analysis of glucose and xylose metabolism in Escherichia coli under aerobic and anaerobic conditions by (13)C metabolic flux analysis.

    Science.gov (United States)

    Gonzalez, Jacqueline E; Long, Christopher P; Antoniewicz, Maciek R

    2017-01-01

    Glucose and xylose are the two most abundant sugars derived from the breakdown of lignocellulosic biomass. While aerobic glucose metabolism is relatively well understood in E. coli, until now there have been only a handful of studies focused on anaerobic glucose metabolism and no (13)C-flux studies on xylose metabolism. In the absence of experimentally validated flux maps, constraint-based approaches such as MOMA and RELATCH cannot be used to guide new metabolic engineering designs. In this work, we have addressed this critical gap in current understanding by performing comprehensive characterizations of glucose and xylose metabolism under aerobic and anaerobic conditions, using recent state-of-the-art techniques in (13)C metabolic flux analysis ((13)C-MFA). Specifically, we quantified precise metabolic fluxes for each condition by performing parallel labeling experiments and analyzing the data through integrated (13)C-MFA using the optimal tracers [1,2-(13)C]glucose, [1,6-(13)C]glucose, [1,2-(13)C]xylose and [5-(13)C]xylose. We also quantified changes in biomass composition and confirmed turnover of macromolecules by applying [U-(13)C]glucose and [U-(13)C]xylose tracers. We demonstrated that under anaerobic growth conditions there is significant turnover of lipids and that a significant portion of CO2 originates from biomass turnover. Using knockout strains, we also demonstrated that β-oxidation is critical for anaerobic growth on xylose. Quantitative analysis of co-factor balances (NADH/FADH2, NADPH, and ATP) for different growth conditions provided new insights regarding the interplay of energy and redox metabolism and the impact on E. coli cell physiology.

  7. Reproducibility of intraperitoneal 2-deoxy-2-[{sup 18}F]-fluoro-D-glucose cerebral uptake in rodents through time

    Energy Technology Data Exchange (ETDEWEB)

    Marsteller, Douglas A. [Graduate Program in Molecular and Cellular Pharmacology, SUNY Stony Brook, Stony Brook, NY 11794-8651 (United States) and Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States)]. E-mail: marst@bnl.gov; Barbarich-Marsteller, Nicole C. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Graduate Program in Neuroscience, Department of Neurobiology and Behavior, SUNY Stony Brook, Stony Brook, NY 11794-5230 (United States); Fowler, Joanna S. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Schiffer, Wynne K. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Alexoff, David L. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Rubins, Daniel J. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Dewey, Stephen L. [Graduate Program in Molecular and Cellular Pharmacology, SUNY Stony Brook, Stony Brook, NY 11794-8651 (United States); Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Graduate Program in Neuroscience, Department of Neurobiology and Behavior, SUNY Stony Brook, Stony Brook, NY 11794-5230 (United States); Psychiatry Department, New York University School of Medicine, New York, NY 10016 (United States)

    2006-01-15

    Introduction: One strength of small animal imaging is the ability to obtain longitudinal measurements within the same animal, effectively reducing the number of animals needed and increasing statistical power. However, the variability of within-rodent brain glucose uptake after an intraperitoneal injection across an extended time has not been measured. Methods: Small animal imaging with 2-deoxy-2-[{sup 18}F]-fluoro-D-glucose ({sup 18}FDG) was used to determine the variability of a 50-min brain {sup 18}FDG uptake following an intraperitoneal injection over time in awake male and female Sprague-Dawley rodents. Results: After determining the variability of an intraperitoneal injection in the awake rat, we found that normalization of brain {sup 18}FDG uptake for (1) injected dose and body weight or (2) body weight, plasma glucose concentration and injected dose resulted in a coefficient of variation (CV) of 15%. However, if we normalized regional uptake to whole brain to compare relative regional changes, the CV was less than 5%. Normalized cerebral {sup 18}FDG uptake values were reproducible for a 2-week period in young adult animals. After 1 year, both male and female animals had reduced whole-brain uptake, as well as reduced regional hippocampal and striatal {sup 18}FDG uptake. Conclusion: Overall, our results were similar to findings in previous rodent and human clinical populations; thus, using a high throughput study with intraperitoneal {sup 18}FDG is a promising preclinical model for clinical populations. This is particularly relevant for measuring changes in brain function after experimental manipulation, such as long-term pharmacological administration.

  8. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

    Science.gov (United States)

    Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

    2012-08-15

    Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity.

  9. Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity.

    Science.gov (United States)

    Xian, Li; Hou, Siyuan; Huang, Zan; Tang, An; Shi, Peiliang; Wang, Qinghua; Song, Anying; Jiang, Shujun; Lin, Zhaoyu; Guo, Shiying; Gao, Xiang

    2015-04-01

    Protein phosphatase 2A (PP2A) is a key negative regulator of phosphatidylinositol 3-kinase/Akt pathway. Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and dyslipidemia. Here we studied the role of liver PP2Ac in glucose metabolism and evaluated whether PP2Ac is a suitable therapeutic target for treating insulin resistance syndrome. Liver-specific Ppp2cα knockout mice (Ppp2cα(loxp/loxp): Alb) exhibited improved glucose homeostasis compared with littermate controls in both normal and high-fat diet conditions, despite no significant changes in body weight and liver weight under chow diet. Ppp2cα(loxp/loxp): Alb mice showed enhanced glycogen deposition, serum triglyceride, cholesterol, low density lipoprotein and high density lipoprotein, activated insulin signaling, decreased expressions of gluconeogenic genes G6P and PEPCK, and lower liver triglyceride. Liver-specific Ppp2cα knockout mice showed enhanced glucose homeostasis and increased insulin sensitivity by activation of insulin signaling through Akt. These findings suggest that inhibition of hepatic Ppp2cα may be a useful strategy for the treatment of insulin resistance syndrome.

  10. 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

  11. Effect of guar gum on glucose and lipid metabolism in white sea bream Diplodus sargus.

    Science.gov (United States)

    Enes, P; Pousão-Ferreira, P; Salmerón, C; Capilla, E; Navarro, I; Gutiérrez, J; Oliva-Teles, A

    2013-04-01

    The aim of this study was to assess the role of soluble non-starch polysaccharide (guar gum) on white sea bream Diplodus sargus, glucose and lipid metabolism. A control diet was formulated to contain 40 % crude protein, 14 % crude lipids and 35 % pregelatinized maize starch, and three other diets were formulated similar to the control diet except for guar gum, which was included at 4 % (diet GG4), 8 % (diet GG8) or 12 % (diet GG12). Diets were fed to the fish for 9 weeks on a pair-feeding scheme. Guar gum had no effect on growth performance, feed efficiency, glycaemia, cholesterolaemia and plasma triacylglyceride levels. Hepatic glucokinase and pyruvate kinase activities, liver glycogen content and liver insulin-like growth factor-I gene expression were not affected by dietary guar gum, while fructose-1,6-bisphosphatase activity was lower in fish fed guar gum-supplemented diets. Hepatic glucose-6-phosphate dehydrogenase activity was higher in fish fed diets GG4 and GG8 than in the control group. Overall, data suggest that in contrast to mammals guar gum had no effect on white sea bream glucose utilization and in lowering plasma cholesterol and triacylglyceride levels. However, it seems to contribute to lower endogenous glucose production.

  12. Developmental role for endocannabinoid signaling in regulating glucose metabolism and growth.

    Science.gov (United States)

    Li, Zhiying; Schmidt, Sarah F; Friedman, Jeffrey M

    2013-07-01

    Treatment of ob/ob (obese) mice with a cannabinoid receptor 1 (Cnr1) antagonist reduces food intake, suggesting a role for endocannabinoid signaling in leptin action. We further evaluated the role of endocannabinoid signaling by analyzing the phenotype of Cnr1 knockout ob/ob mice. Double mutant animals show a more severe growth retardation than ob/ob mice with similar levels of adiposity and reduced IGF-I levels without alterations of growth hormone (GH) levels. The double mutant mice are also significantly more glucose intolerant than ob/ob mice. This is in contrast to treatment of ob/ob mice with a Cnr1 antagonist that had no effect on glucose metabolism, suggesting a possible requirement for endocannabinoid signaling during development for normal glucose homeostasis. Double mutant animals also showed similar leptin sensitivity as ob/ob mice, suggesting that there are developmental changes that compensate for the loss of Cnr1 signaling. These data establish a role for Cnr1 during development and suggest that compensatory changes during development may mitigate the requirement for Cnr1 in mediating the effects of leptin. The data also suggest a developmental role for Cnr1 to promote growth, regulate the GH/IGF-I axis, and improve β-cell function and glucose homeostasis in the setting of leptin deficiency.

  13. Effect of pinitol on glucose metabolism and adipocytokines in uncontrolled type 2 diabetes.

    Science.gov (United States)

    Kim, Mi Jin; Yoo, Kwang Ha; Kim, Ji Hoon; Seo, Young Tak; Ha, Byung Wook; Kho, Jang Hyun; Shin, Young Goo; Chung, Choon Hee

    2007-09-01

    Pinitol (3-O-methyl-D-chiro-inositol) was identified in putative insulin mediator fractions that have hypoglycemic activity, and appears to mimic the act effects of insulin by acting downstream in the insulin signaling pathway. We evaluated the effect of pinitol therapy in type 2 diabetic patients who were poorly controlled with hypoglycemic drugs, such as sulfonylurea, metformin and/or insulin. Twenty type 2 diabetic patients were enrolled in our study. Fasting glucose, fasting c-peptide, total cholesterol, triglyceride, and HDL- and LDL-cholesterol were checked before and after a 12-week pinitol treatment (20 mg kg(-1)day(-1)). All subjects continued their current medications during the study. Adipocytokines, such as adiponectin, leptin, free fatty acids, and c-reactive protein (CRP) were checked before and after pinitol treatment. After pinitol treatment, fasting glucose, post-prandial glucose levels, and hemoglobin A1c were significantly decreased (Ppinitol treatment. In the unresponsive group, serum c-peptide levels were higher than in the responsive group. Twelve weeks of pinitol treatment altered glucose metabolism, but not lipid profiles or adipocytokine levels, in type 2 diabetic patients. Additional research is needed to define the physiological and potential therapeutic effects of pinitol administration.

  14. Evaluation of Chios mastic gum on lipid and glucose metabolism in diabetic mice.

    Science.gov (United States)

    Georgiadis, Ioannis; Karatzas, Theodore; Korou, Laskarina-Maria; Agrogiannis, George; Vlachos, Ioannis S; Pantopoulou, Alkisti; Tzanetakou, Irene P; Katsilambros, Nikolaos; Perrea, Despina N

    2014-03-01

    Chios mastic gum (MG), a resin produced from Pistacia lentiscus var. Chia, is reported to possess beneficial cardiovascular and hepatoprotective properties. This study investigated the effect of crude Chios MG on metabolic parameters in diabetic mice. Streptozotocin-induced diabetic 12-week-old male C57bl/6 mice were assigned to three groups: NC (n=9) control; LdM (n=9) animals receiving low dose mastic for 8 weeks (20 mg/kg body weight [BW]); and HdM (n=9) animals receiving high dose mastic (500 mg/kg BW) for the same period. Serum lipid and glucose levels were determined at baseline, at 4 and 8 weeks. Serum total protein, adiponectin, and resistin levels were also measured at the end of the experiment. Histopathological examination for liver, kidney, aorta, and heart lesions was performed. After 4 weeks, MG administration resulted in decreased serum glucose and triglyceride levels in both LdM and HdM, whereas BW levels were reduced in LdM group compared with controls. At the end of the experiment, LdM presented significantly lower serum glucose, cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improved high-density lipoprotein cholesterol levels compared with control group. HdM group had ameliorated serum triglyceride levels. Hepatic steatosis observed in control group was partially reversed in LdM and HdM groups. MG administered in low dosages improves glucose and lipid disturbances in diabetic mice while alleviating hepatic damage.

  15. Metabolic Control of Type 2 Diabetes by Targeting the GLUT4 Glucose Transporter: Intervention Approaches.

    Science.gov (United States)

    Alam, Fahmida; Islam, Md Asiful; Khalil, Md Ibrahim; Gan, Siew Hua

    2016-01-01

    Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is characterized by insulin resistance in the hepatic and peripheral tissues. Glucose transporter 4 (GLUT4) plays a major role in the pathophysiology of T2DM. Its defective expression or translocation to the peripheral cell plasma membrane in T2DM patients hinders the entrance of glucose into the cell for energy production. In addition to suitable drugs, an appropriate diet and/or exercise can be implemented to target the increase in GLUT4 expression, GLUT4 concentrations and GLUT4 translocation to the cell surface when managing the glucose metabolism of T2DM patients. In this review, we discussed successful intervention strategies that were individually administered or coupled with diet and/or exercise and affected the expression and translocation of GLUT4 in T2DM while reducing the excess glucose load from the blood. Additionally, some potentially good synthetic and natural compounds, which can activate the insulin-independent GLUT4 signaling pathways for the efficient management of T2DM, are highlighted as possible targets or emerging alternative sources for future anti-diabetic drug development.

  16. Cyclooxygenase-derived vasoconstriction restrains hypoxia-mediated cerebral vasodilation in young adults with metabolic syndrome.

    Science.gov (United States)

    Harrell, John W; Schrage, William G

    2014-01-15

    Poor cerebrovascular function in metabolic syndrome (MetSyn) likely contributes to elevated risk of cerebrovascular disease in this growing clinical population. Younger MetSyn adults without clinical evidence of cerebrovascular disease exhibit preserved hypercapnic vasodilation yet markedly impaired hypoxic vasodilation, but the mechanisms behind reduced hypoxic vasodilation are unknown. Based on data from rats, we tested the hypothesis that younger adults with MetSyn exhibit reduced cerebral hypoxic vasodilation due to loss of vasodilating prostaglandins. Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in adults with MetSyn (n = 13, 33 ± 3 yr) and healthy controls (n = 15, 31 ± 2 yr). Isocapnic hypoxia was induced by titrating inspired oxygen to lower arterial saturation to 90% and 80% for 5 min each. Separately, hypercapnia was induced by increasing end-tidal CO2 10 mmHg above baseline levels. Cyclooxygenase inhibition (100 mg indomethacin) was conducted in a randomized double-blind, placebo controlled design. MCAv was normalized for group differences in blood pressure (healthy: 89 ± 2 mmHg vs. MetSyn: 102 ± 2 mmHg) as cerebrovascular conductance index (CVCi), and used to assess cerebral vasodilation. Hypoxia increased CVCi in both groups; however, vasodilation was ∼55% lower in MetSyn at SpO2 = 80% (P vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P vasodilation was similar between groups, as was the decrease in vasodilation with indomethacin. These data indicate increased production of vasoconstrictor prostaglandins restrains hypoxic cerebral vasodilation in MetSyn, preventing them from responding appropriately to this important physiological stressor.

  17. Hyperosmolar sodium chloride is toxic to cultured neurons and causes reduction of glucose metabolism and ATP levels, an increase in glutamate uptake, and a reduction in cytosolic calcium.

    Science.gov (United States)

    Morland, Cecilie; Pettersen, Mi Nguyen; Hassel, Bjørnar

    2016-05-01

    Elevation of serum sodium, hypernatremia, which may occur during dehydration or treatment with sodium chloride, may cause brain dysfunction and damage, but toxic mechanisms are poorly understood. We found that exposure to excess NaCl, 10-100mmol/L, for 20h caused cell death in cultured cerebellar granule cells (neurons). Toxicity was due to Na(+), since substituting excess Na(+) with choline reduced cell death to control levels, whereas gluconate instead of excess Cl(-) did not. Prior to cell death from hyperosmolar NaCl, glucose consumption and lactate formation were reduced, and intracellular aspartate levels were elevated, consistent with reduced glycolysis or glucose uptake. Concomitantly, the level of ATP became reduced. Pyruvate, 10mmol/L, reduced NaCl-induced cell death. The extracellular levels of glutamate, taurine, and GABA were concentration-dependently reduced by excess NaCl; high-affinity glutamate uptake increased. High extracellular [Na(+)] caused reduction in intracellular free [Ca(2+)], but a similar effect was seen with mannitol, which was not neurotoxic. We suggest that inhibition of glucose metabolism with ensuing loss of ATP is a neurotoxic mechanism of hyperosmolar sodium, whereas increased uptake of extracellular neuroactive amino acids and reduced intracellular [Ca(2+)] may, if they occur in vivo, contribute to the cerebral dysfunction and delirium described in hypernatremia.

  18. Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor.

    Science.gov (United States)

    Kern, Simone; Oakes, Terrence R; Stone, Charles K; McAuliff, Emelia M; Kirschbaum, Clemens; Davidson, Richard J

    2008-05-01

    The prefrontal cortex (PFC) has been well known for its role in higher order cognition, affect regulation and social reasoning. Although the precise underpinnings have not been sufficiently described, increasing evidence also supports a prefrontal involvement in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation during a psychosocial stress exposure in 14 healthy humans. Regional brain metabolism was assessed using positron emission tomography (PET) and injection of fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC, increased glucose metabolic rate was associated with lower or higher salivary cortisol concentration in response to a psychosocial stress condition. Metabolic glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was negatively associated with stress-induced salivary cortisol increases. Furthermore, metabolic glucose rate in these regions was inversely coupled with changes in glucose metabolic rate in other areas, known to be involved in HPA axis regulation such as the amygdala/hippocampal region. In contrast, metabolic glucose rate in areas more lateral to the mPFC was positively associated with saliva cortisol. Subjective ratings on task stressfulness, task controllability and self-reported dispositional mood states also showed positive and negative associations with the glucose metabolic rate in prefrontal regions. These findings suggest that in humans, the PFC is activated in response to psychosocial stress and distinct prefrontal metabolic glucose patterns are linked to endocrine stress measures as well as subjective ratings on task stressfulness, controllability as well as dispositional mood states.

  19. Glucose as the Sole Metabolic Fuel: Overcoming a Misconception Using Conceptual Change to Teach the Energy-Yielding Metabolism to Brazilian High School Students

    Science.gov (United States)

    Luz, Mauricio R. M. P.; Oliveira, Gabriel A.; Da Poian, Andrea T.

    2013-01-01

    A misconception regarding the human metabolism has been shown to be widespread among high school students. The students consider glucose as the sole metabolic fuel, disregarding that lipids and amino acids can be oxidized for ATP production by human cells. This misconception seems to be a consequence of formal teaching in grade and high schools.…

  20. Cerebral blood flow and oxygen metabolism in dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Yoshitomo; Takahashi, Satoshi; Yonezawa, Hisashi [Iwate Medical Univ., Morioka (Japan). School of Medicine

    2000-06-01

    Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO{sub 2}) and the oxygen extraction fraction (rOEF) were measured using the steady-state {sup 15}O technique and positron emission tomography (PET) in six patients with dementia with Lewy bodies (DLB), and compared with ten patients with Alzheimer disease (AD) and six normal controls. In the AD patients, rCBF and rCMRO{sub 2} were significantly decreased in the frontal, parietal, and temporal cortices compared with controls. In DLB patients, rCBF and rCMRO{sub 2} were decreased in the frontal, parietal, temporal, and occipital cortices compared with controls, and were decreased more diffusely than in AD patients. rCBF and rCMRO{sub 2} were significantly decreased in occipital cortex compared with AD patients. rOEF was significantly increased in the parieto-temporal cortex in AD patients compared with controls. In DLB patients, rOEF was significantly increased not only in the parieto-temporal cortex but also in the occipital and frontal cortices compared with controls, and was significantly increased in the occipital cortex compared with AD patients. The diffuse reduction of cerebral blood flow and oxygen metabolism including the occipital cortex may be related to visual hallucination and other visuospatial deficits frequently seen in DLB patients. The increase in rOEF may be mainly due to the reduction in the vascular bed associated with decreased activity in the vasodilatory cholinergic system. (author)

  1. Preliminary validation of an exercise program suitable for pregnant women with abnormal glucose metabolism: inhibitory effects of Tai Chi Yuttari-exercise on plasma glucose elevation

    Science.gov (United States)

    Yamamoto, Sachina; Kagawa, Kyoko; Hori, Naohi; Akezaki, Yoshiteru; Mori, Kohei; Nomura, Takuo

    2016-01-01

    [Purpose] There is insufficient evidence related to exercise programs that are safe and efficacious for pregnant women with abnormal glucose metabolism. Tai Chi Yuttari-exercise is an exercise program with validated safety and efficacy in improving physical function in the elderly. In this study, we investigated this program’s inhibitory effects on plasma glucose elevation when it was adapted to a pregnancy model. [Subjects and Methods] Twelve 18- to 19-year-old females without a history of pregnancy were randomly assorted into two groups: an intervention group, for which six subjects were outfitted with mock-pregnancy suits and asked to perform Tai Chi Yuttari-exercise, and a control group who did not perform exercise. The intervention group had a mean Borg Scale score of 11.1 ± 0.9 during the exercise. [Results] No significant intragroup differences were observed in fasting, baseline, or post-intervention/observation plasma glucose levels. On the other hand, the intergroup change in plasma glucose levels after intervention/observation was significant when comparing the intervention and control groups: −1.66 ± 7.0 and 9.42 ± 6.57 mg/dl, respectively. [Conclusion] Tai Chi Yuttari-exercise appears to effectively inhibit plasma glucose elevation at intensity and movement levels that can be safely applied to pregnant women with abnormal glucose metabolism. PMID:28174463

  2. Enhanced metabolic capacity of the frontal cerebral cortex after Pavlovian conditioning.

    Science.gov (United States)

    Bruchey, A K; Gonzalez-Lima, F

    2008-03-18

    While Pavlovian conditioning alters stimulus-evoked metabolic activity in the cerebral cortex, less is known about the effects of Pavlovian conditioning on neuronal metabolic capacity. Pavlovian conditioning may increase prefrontal cortical metabolic capacity, as suggested by evidence of changes in cortical synaptic strengths, and evidence for a shift in memory initially processed in subcortical regions to more distributed prefrontal cortical circuits. Quantitative cytochrome oxidase histochemistry was used to measure cumulative changes in brain metabolic capacity associated with both cued and contextual Pavlovian conditioning in rats. The cued conditioned group received tone-foot-shock pairings to elicit a conditioned freezing response to the tone conditioned stimulus, while the contextually conditioned group received pseudorandom tone-foot-shock pairings in an excitatory context. Untrained control group was handled daily, but did not receive any tone presentations or foot shocks. The cued conditioned group had higher cytochrome oxidase activity in the infralimbic and anterior cingulate cortex, and lower cytochrome oxidase activity in dorsal hippocampus than the other two groups. A significant increase in cytochrome oxidase activity was found in anterior cortical areas (medial, dorsal and lateral frontal cortex; agranular insular cortex; lateral and medial orbital cortex and prelimbic cortex) in both conditioned groups, as compared with the untrained control group. In addition, no differences in cytochrome oxidase activity in the somatosensory regions and the amygdala were detected among all groups. The findings indicate that cued and contextual Pavlovian conditioning induces sustained increases in frontal cortical neuronal metabolic demand resulting in regional enhancement in the metabolic capacity of anterior cortical regions. Enhanced metabolic capacity of these anterior cortical areas after Pavlovian conditioning suggests that the frontal cortex may play a

  3. 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.

  4. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2011-12-01

    Full Text Available The insulin/IGF-activated AKT signaling pathway plays a crucial role in regulating tissue growth and metabolism in multicellular animals. Although core components of the pathway are well defined, less is known about mechanisms that adjust the sensitivity of the pathway to extracellular stimuli. In humans, disturbance in insulin sensitivity leads to impaired clearance of glucose from the blood stream, which is a hallmark of diabetes. Here we present the results of a genetic screen in Drosophila designed to identify regulators of insulin sensitivity in vivo. Components of the MAPK/ERK pathway were identified as modifiers of cellular insulin responsiveness. Insulin resistance was due to downregulation of insulin-like receptor gene expression following persistent MAPK/ERK inhibition. The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels.

  5. Polychlorinated biphenyl exposure and glucose metabolism in Danish children aged 9 years

    DEFF Research Database (Denmark)

    Jensen, Tina K; Timmermann, Clara Amalie Gade; Rossing, Laura I;

    2014-01-01

    and participants: A total of 771 healthy Danish third grade school children aged 8-10 years in the municipality of Odense were recruited in 1997 through a two-stage cluster sampling from 25 different schools stratified according to location and socioeconomic character; 509 (9.7±0.8 years, 53% girls) had adequate......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......-DDE. Conclusion: A strong inverse association between serum insulin and PCB exposure was found while fasting plasma glucose remained within the expected narrow range. Our findings suggest that PCB may not exert effect through decreased peripheral insulin sensitivity, as seen in obese and low fit children...

  6. 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

    2012-09-04

    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.

  7. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Drew, Brian G; Duffy, Stephen J; Formosa, Melissa F

    2009-01-01

    kinase kinase and the AMP-activated protein kinase pathway. CONCLUSIONS: rHDL reduced plasma glucose in patients with type 2 diabetes mellitus by increasing plasma insulin and activating AMP-activated protein kinase in skeletal muscle. These findings suggest a role for HDL-raising therapies beyond......BACKGROUND: Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP...... baseline occurred during rHDL than during placebo (at 4 hours rHDL=-2.6+/-0.4; placebo=-2.1+/-0.3 mmol/L; P=0.018). rHDL increased plasma insulin (at 4 hours rHDL=3.4+/-10.0; placebo= -19.2+/-7.4 pmol/L; P=0.034) and also the homeostasis model assessment beta-cell function index (at 4 hours rHDL=18...

  8. RATIONALE FOR PREVENTION OF CARDIO-CEREBRAL COMPLICATIONS IN THE METABOLIC SYNDROME BASED ON MATHEMATICAL FORECASTING TECHNIQUES

    Directory of Open Access Journals (Sweden)

    S. V. Chernavskii

    2011-01-01

    Full Text Available Objective — to study prevention of cardio-cerebral complications of metabolic syndrome on the basis of mathematical methods of forecasting.Subjects and methods. A discriminant analysis of clinical and instrumental data of patients with MS.Results of this study allow the early (prenosological stages of the metabolic syndrome using the linear discriminant equations to predict thedevelopment of myocardial infarction up to 89.3 %, stroke — up to 87.8 %.Conclusion. The diagnostic and treatment algorithms developed based on the stratification of cardiovascular risk index, allow us to give sound recommendations for targeted prevention of cardio-cerebral complications.

  9. Effects of the BET-inhibitor, RVX-208 on the HDL lipidome and glucose metabolism in individuals with prediabetes

    DEFF Research Database (Denmark)

    Siebel, Andrew L; Trinh, Si Khiang; Formosa, Melissa F

    2016-01-01

    particle size and distribution using NMR spectroscopy. An oral glucose tolerance test (OGTT) protocol with oral and infused stable isotope tracers was employed to assess postprandial plasma glucose, indices of insulin secretion and insulin sensitivity, glucose kinetics and lipolysis. Whole plasma and HDL...... (HDL lipidome) and glucose metabolism. MATERIALS AND METHODS: Twenty unmedicated males with prediabetes received 100mg b.i.d. RVX-208 and placebo for 29-33days separated by a wash-out period in a randomized, cross-over design trial. Plasma HDL-cholesterol and apoA-I were assessed as well as lipoprotein...

  10. Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Egstrup, M; Kistorp, C N; Schou, M;

    2013-01-01

    years, 69% male, 59% had ischaemic heart disease, mean LV ejection fraction (LVEF) 37 ± 9%). Thirty-four (21%) patients had known diabetes mellitus (DM). Oral glucose tolerance testing (OGTT) classified patients without a prior DM diagnosis as normal glucose tolerance (NGT), impaired glucose tolerance......AIMS: To investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF). METHODS AND RESULTS: From an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10...... detected by OGTT, is independently associated with reduced LV contractile reserve and exercise...

  11. 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.

  12. Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

    Institute of Scientific and Technical Information of China (English)

    LIU Huan-guang; YANG An-chao; MENG Da-wei; ZHANG Kai; ZHANG Jian-guo

    2012-01-01

    Background Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures.In this study,we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.Methods Three groups of rats were used:(1) a stimulation group (n=12),(2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA),and (3) a control group (n=12) with sham surgery.Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT.High-frequency stimulation was performed in each group except the sham stimulation group.Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in thestimulation group.The concentrations of glucose,lactate,and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.Results The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020,P=0.001; respectively).However,no significant difference in the concentration of glucose and pyruvate was found between these groups (P>0.05).Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05),but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).Conclusions This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation.These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

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

    Science.gov (United States)

    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 transporter (GLUT)1, and hexokinase-II was measured by quantitative polymerase chain reaction. The levels of LDH and β subunit of human F1-F0 adenosine triphosphate synthase (β-F1-ATPase) were detected by enzyme-linked immunosorbent and western blot assays. The HL-60 and HL-60/ADR cell lines were used to evaluate glycolytic activity and effect of glycolysis inhibition on cellular proliferation and apoptosis. Drug-resistant HL-60/ADR cells exhibited a significantly increased level of glycolysis compared with the drug-sensitive HL-60 cell line. The expression of HIF-1α, hexokinase-II, GLUT1 and LDH were increased in AML patients with no remission (NR), compared to healthy control individuals and patients with complete remission (CR) and partial remission. The expression of β-F1-ATPase in patients with NR was decreased compared with the expression in the CR group. Treatment of HL-60/ADR cells with 2-deoxy-D-glucose or 3-bromopyruvate increased in vitro sensitivity to Adriamycin (ADR), while treatment of HL-60 cells did not affect drug cytotoxicity. Subsequent to treatment for 24 h, apoptosis in these two cell lines showed no significant difference. However, glycolytic inhibitors in combination with ADR increased cellular necrosis. These findings indicate that increased glycolysis and low efficiency of oxidative phosphorylation may contribute to drug resistance. Targeting glycolysis is a viable strategy for modulating chemoresistance in AML. PMID:27347147

  14. 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.

  15. Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer's disease.

    Science.gov (United States)

    Oh, Hwamee; Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

    2016-08-01

    SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P Alzheimer's disease-related hypometabolism was observed in brain regions that showed both age-invariance and amyloid-β-related increases in glucose metabolism. Our results indicate that although

  16. 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

  17. 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.

  18. Lactate transport and receptor actions in cerebral malaria

    DEFF Research Database (Denmark)

    Mariga, Shelton T; Kolko, Miriam; Gjedde, Albert

    2014-01-01

    Cerebral malaria (CM), caused by Plasmodium falciparum infection, is a prevalent neurological disorder in the tropics. Most of the patients are children, typically with intractable seizures and high mortality. Current treatment is unsatisfactory. Understanding the pathogenesis of CM is required...... in order to identify therapeutic targets. Here, we argue that cerebral energy metabolic defects are probable etiological factors in CM pathogenesis, because malaria parasites consume large amounts of glucose metabolized mostly to lactate. Monocarboxylate transporters (MCTs) mediate facilitated transfer...

  19. Emerging roles of the myocardin family of proteins in lipid and glucose metabolism.

    Science.gov (United States)

    Swärd, Karl; Stenkula, Karin G; Rippe, Catarina; Alajbegovic, Azra; Gomez, Maria F; Albinsson, Sebastian

    2016-09-01

    Members of the myocardin family bind to the transcription factor serum response factor (SRF) and act as coactivators controlling genes of relevance for myogenic differentiation and motile function. Binding of SRF to DNA is mediated by genetic elements called CArG boxes, found often but not exclusively in muscle and growth controlling genes. Studies aimed at defining the full spectrum of these CArG elements in the genome (i.e. the CArGome) have in recent years, unveiled unexpected roles of the myocardin family proteins in lipid and glucose homeostasis. This coactivator family includes the protein myocardin (MYOCD), the myocardin-related transcription factors A and B (MRTF-A/MKL1 and MRTF-B/MKL2) and MASTR (MAMSTR). Here we discuss growing evidence that SRF-driven transcription is controlled by extracellular glucose through activation of the Rho-kinase pathway and actin polymerization. We also describe data showing that adipogenesis is influenced by MLK activity through actions upstream of peroxisome proliferator-activated receptor γ with consequences for whole body fat mass and insulin sensitivity. The recently demonstrated involvement of myocardin coactivators in the biogenesis of caveolae, Ω-shaped membrane invaginations of importance for lipid and glucose metabolism, is finally discussed. These novel roles of myocardin proteins may open the way for new unexplored strategies to combat metabolic diseases such as diabetes, which, at the current incidence, is expected to reach 333 million people worldwide by 2025. This review highlights newly discovered roles of myocardin-related transcription factors in lipid and glucose metabolism as well as novel insights into their well-established role as mediators of stretch-dependent effects in smooth muscle. As co-factors for serum response factor (SRF), MKLs regulates transcription of genes involved in the contractile function of smooth muscle cells. In addition to mechanical stimuli, this regulation has now been found to

  20. Metabolic engineering of Corynebacterium glutamicum to produce GDP-L-fucose from glucose and mannose.

    Science.gov (United States)

    Chin, Young-Wook; Park, Jin-Byung; Park, Yong-Cheol; Kim, Kyoung Heon; Seo, Jin-Ho

    2013-06-01

    Wild-type Corynebacterium glutamicum was metabolically engineered to convert glucose and mannose into guanosine 5'-diphosphate (GDP)-L-fucose, a precursor of fucosyl-oligosaccharides, which are involved in various biological and pathological functions. This was done by introducing the gmd and wcaG genes of Escherichia coli encoding GDP-D-mannose-4,6-dehydratase and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase, respectively, which are known as key enzymes in the production of GDP-L-fucose from GDP-D-mannose. Coexpression of the genes allowed the recombinant C. glutamicum cells to produce GDP-L-fucose in a minimal medium containing glucose and mannose as carbon sources. The specific product formation rate was much higher during growth on mannose than on glucose. In addition, the specific product formation rate was further increased by coexpressing the endogenous phosphomanno-mutase gene (manB) and GTP-mannose-1-phosphate guanylyl-transferase gene (manC), which are involved in the conversion of mannose-6-phosphate into GDP-D-mannose. However, the overexpression of manA encoding mannose-6-phosphate isomerase, catalyzing interconversion of mannose-6-phosphate and fructose-6-phosphate showed a negative effect on formation of the target product. Overall, coexpression of gmd, wcaG, manB and manC in C. glutamicum enabled production of GDP-L-fucose at the specific rate of 0.11 mg g cell(-1) h(-1). The specific GDP-L-fucose content reached 5.5 mg g cell(-1), which is a 2.4-fold higher than that of the recombinant E. coli overexpressing gmd, wcaG, manB and manC under comparable conditions. Well-established metabolic engineering tools may permit optimization of the carbon and cofactor metabolisms of C. glutamicum to further improve their production capacity.

  1. Zonation of nitrogen and glucose metabolism gene expression upon acute liver damage in mouse.

    Directory of Open Access Journals (Sweden)

    Shahrouz Ghafoory

    Full Text Available Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose homeostasis and detoxification. To analyze damage and regeneration of liver tissue in response to a toxic agent, expression of liver specific enzymes was analyzed by in situ hybridization in mouse over a 6 days time course following carbon tetrachloride (CCl4 injection. CCl4 mixed with mineral oil was administered to BALB/c mice by intraperitoneal injection, and mice were sacrificed at different time points post injection. Changes in the expression of albumin (Alb, arginase (Arg1, glutaminase 2 (Gls2, Glutamine synthetase (Gs, glucose-6-phosphatase (G6pc, glycogen synthase 2 (Gys2, Glycerinaldehyd-3-phosphat-Dehydrogenase (Gapdh, Cytochrom p450 2E1 (Cyp2e1 and glucagon receptor (Gcgr genes in the liver were studied by in situ hybridization and qPCR. We observed significant changes in gene expression of enzymes involved in nitrogen and glucose metabolism and their local distribution following CCl4 injury. We also found that Cyp2e1, the primary metabolizing enzyme for CCl4, was strongly expressed in the pericentral zone during recovery. Furthermore, cells in the damaged area displayed distinct gene expression profiles during the analyzed time course and showed complete recovery with strong albumin production 6 days after CCl4 injection. Our results indicate that despite severe damage, liver cells in the damaged area do not simply die but instead display locally adjusted gene expression supporting damage response and recovery.

  2. Zonation of Nitrogen and Glucose Metabolism Gene Expression upon Acute Liver Damage in Mouse

    Science.gov (United States)

    Ghafoory, Shahrouz; Breitkopf-Heinlein, Katja; Li, Qi; Scholl, Catharina; Dooley, Steven; Wölfl, Stefan

    2013-01-01

    Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose homeostasis and detoxification. To analyze damage and regeneration of liver tissue in response to a toxic agent, expression of liver specific enzymes was analyzed by in situ hybridization in mouse over a 6 days time course following carbon tetrachloride (CCl4) injection. CCl4 mixed with mineral oil was administered to BALB/c mice by intraperitoneal injection, and mice were sacrificed at different time points post injection. Changes in the expression of albumin (Alb), arginase (Arg1), glutaminase 2 (Gls2), Glutamine synthetase (Gs), glucose-6-phosphatase (G6pc), glycogen synthase 2 (Gys2), Glycerinaldehyd-3-phosphat-Dehydrogenase (Gapdh), Cytochrom p450 2E1 (Cyp2e1) and glucagon receptor (Gcgr) genes in the liver were studied by in situ hybridization and qPCR. We observed significant changes in gene expression of enzymes involved in nitrogen and glucose metabolism and their local distribution following CCl4 injury. We also found that Cyp2e1, the primary metabolizing enzyme for CCl4, was strongly expressed in the pericentral zone during recovery. Furthermore, cells in the damaged area displayed distinct gene expression profiles during the analyzed time course and showed complete recovery with strong albumin production 6 days after CCl4 injection. Our results indicate that despite severe damage, liver cells in the damaged area do not simply die but instead display locally adjusted gene expression supporting damage response and recovery. PMID:24147127

  3. Glucose and Glycogen Metabolism in Brugia malayi Is Associated with Wolbachia Symbiont Fitness.

    Science.gov (United States)

    Voronin, Denis; Bachu, Saheed; Shlossman, Michael; Unnasch, Thomas R; Ghedin, Elodie; Lustigman, Sara

    2016-01-01

    Wolbachia are endosymbiotic bacteria found in the majority of arthropods and filarial nematodes of medical and veterinary importance. They have evolved a wide range of symbiotic associations. In filarial nematodes that cause human lymphatic filariasis (Wuchereria bancrofti, Brugia malayi) or onchocerciasis (Onchocerca volvulus), Wolbachia are important for parasite development, reproduction and survival. The symbiotic bacteria rely in part on nutrients and energy sources provided by the host. Genomic analyses suggest that the strain of Wolbachia found in B. malayi (wBm) lacks the genes for two glycolytic enzymes--6-phosphofructokinase and pyruvate kinase--and is thus potentially unable to convert glucose into pyruvate, an important substrate for energy generation. The Wolbachia surface protein, wBm00432, is complexed to six B. malayi glycolytic enzymes, including aldolase. In this study we characterized two B. malayi aldolase isozymes and found that their expression is dependent on Wolbachia fitness and number. We confirmed by immuno-transmission electron microscopy that aldolase is associated with the Wolbachia surface. RNAi experiments suggested that aldolase-2 plays a significant role in both Wolbachia survival and embryogenesis in B. malayi. Treatment with doxycycline reduced Wolbachia fitness and increased the amount of both glucose and glycogen detected in the filarial parasite, indicating that glucose metabolism and glycogen storage in B. malayi are associated with Wolbachia fitness. This metabolic co-dependency between Wolbachia and its filarial nematode indicates that glycolysis could be a shared metabolic pathway between the bacteria and B. malayi, and thus a potential new target for anti-filarial therapy.

  4. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy. Assessment by F-18-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Toshiisa [Osaka Univ., Suita (Japan). Medical School; Ishida, Yoshio; Hayashida, Kohei [and others

    1998-04-01

    In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75{+-}0.34%, 0.65{+-}0.25%, and 0.43{+-}0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17{+-}0.49%, 0.80{+-}0.44% and 0.99{+-}0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38{+-}0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy. (author)

  5. 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.

  6. Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Johan W.E. Jocken

    2014-10-01

    Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

  7. The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples

    DEFF Research Database (Denmark)

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

    2008-01-01

    not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling...... networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated...

  8. 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

    tolerance test before discharge. LV function was assessed using echocardiographic measurements (LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, restrictive diastolic filling pattern, early transmitral flow velocity to early diastolic mitral annular velocity ratio [E/e'], and left...... 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)

  9. Effects of Chinese herbal medicine on plasma glucose, protein and energy metabolism in sheep

    Institute of Scientific and Technical Information of China (English)

    Xi Liang; Kyota Yamazaki; Mohammad Kamruzzaman; Xue Bi; Arvinda Panthee; Hiroaki Sano

    2014-01-01

    Background:The use of antibiotics in animal diets is facing negative feedback due to the hidden danger of drug residues to human health. Traditional Chinese herbal medicine has been used to replace antibiotics in the past two decades and played an increasingly important role in livestock production. The present study was carried out to assess the feeding effects of a traditional nourishing Chinese herbal medicine mixture on kinetics of plasma glucose, protein and energy metabolism in sheep. Ruminal fermentation characteristics were also determined. Methods:Four sheep were fed on either mixed hay (MH-diet) or MH-diet supplemented with 2%of Chinese herbal medicine (mixture of Astragalus root, Angelica root and Atractylodes rhizome;CHM-diet) over two 35-day periods using a crossover design. The turnover rate of plasma glucose was measured with an isotope dilution method using [U-13C]glucose. The rates of plasma leucine turnover and leucine oxidation, whole body protein synthesis (WBPS) and metabolic heat production were measured using the [1-13C]leucine dilution and open circuit calorimetry. Results:Body weight gain of sheep was higher (P=0.03) for CHM-diet than for MH-diet. Rumen pH was lower (P=0.02), concentration of rumen total volatile fatty acid tended to be higher (P=0.05) and acetate was higher (P=0.04) for CHM-diet than for MH-diet. Turnover rates of plasma glucose and leucine did not differ between diets. Oxidation rate of leucine tended to be higher (P=0.06) for CHM-diet than for MH-diet, but the WBPS did not differ between diets. Metabolic heat production tended to be greater (P=0.05) for CHM-diet than for MH-diet. Conclusions:The sheep fed on CHM-diet had a higher body weight gain and showed positive impacts on rumen fermentation and energy metabolism without resulting in any adverse response. Therefore, these results suggested that the Chinese herbal medicine mixture should be considered as a potential feed additive for sheep.

  10. PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2015-12-01

    Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

  11. PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2012-01-01

    Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

  12. Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice.

    Science.gov (United States)

    Asirvatham-Jeyaraj, Ninitha; Fiege, Jessica K; Han, Ruijun; Foss, Jason; Banek, Christopher T; Burbach, Brandon J; Razzoli, Maria; Bartolomucci, Alessandro; Shimizu, Yoji; Panoskaltsis-Mortari, Angela; Osborn, John W

    2016-10-01

    Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high-fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low-fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8±1.5 mm Hg in sham versus 96.6±6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model.

  13. Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic treatment

    Institute of Scientific and Technical Information of China (English)

    XU Leping; JI Juying; DUAN Yiyang; SHI Hui; ZHANG Bin; SHAO Yaqin; SUN Jian

    2007-01-01

    The aim of this study was to observe the changes in glucose metabolism after antipsychotic(APS)therapy,to note the influencing factors,as well as to dicuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin(HbA1c)levels.One hundred and fifty-two patients with schizophrenia,whose fasting plasma glucose(FPG)and 2-h plasma glucose (2hPG)in the oral glucose tolerance test(2HPG)were normal,were grouped according to the HbA1c levels,one normal and the other abnormal,and were randomly enrolled into risperidone,clozapine and chlorpromazine treatment for six weeks.The FPG and 2hPG were measured at the baseline and at the end of the study.In the group with abnormal HbA1c and clozapine therapy,2HPG was higher after the study[(9.5±1.8)mmol/L]than that before the study[(7.2±1.4)mmol/L]and the difierence was statistically significant(P<0.01).FPG had no statistically significant difference before and after the study in any group(P>0.05).HbA1c levels and drugs contributing to 2HPG at the end of study had statistical cross-action(P<0.01).In the abnormal HbA1c group,2HPG after the study was higher in the clozapine treatment group [(9.5±1.8)mmol/L]than in the risperidone treatment group [(7.4±1.7)mmol/L]and the chlorpromazine treatment group[(7.3±1.6)mmol/L].The differences were statistically significant(P<0.01).In the normal HbA1c group there was no statistically significant difierence before and after the study in any group(P>0.05).2HPG before[(7.1±1.6)mmol/L]and after the study[(8.1±1.9)mmol/L]was higher in the abnormal HbA1c group than in the normal HbA1c group[(6.2±1.4)mmol/L vs(6.5±1.4)mmol/L]with the difierence being statistically significant(P<0.01 vs P<0.001).As compared with normal HbA1c group,the relative risk (RR)of glucose metabolism disease occurrence was 4.7 in the abnormal HDA1C group wlth the difierence being statistically significant(P<0.001).Patients with abnormal HbA1c

  14. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

    Directory of Open Access Journals (Sweden)

    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  15. Glucose metabolism: focus on gut microbiota, the endocannabinoid system and beyond.

    Science.gov (United States)

    Cani, P D; Geurts, L; Matamoros, S; Plovier, H; Duparc, T

    2014-09-01

    The gut microbiota is now considered as a key factor in the regulation of numerous metabolic pathways. Growing evidence suggests that cross-talk between gut bacteria and host is achieved through specific metabolites (such as short-chain fatty acids) and molecular patterns of microbial membranes (lipopolysaccharides) that activate host cell receptors (such as toll-like receptors and G-protein-coupled receptors). The endocannabinoid (eCB) system is an important target in the context of obesity, type 2 diabetes (T2D) and inflammation. It has been demonstrated that eCB system activity is involved in the control of glucose and energy metabolism, and can be tuned up or down by specific gut microbes (for example, Akkermansia muciniphila). Numerous studies have also shown that the composition of the gut microbiota differs between obese and/or T2D individuals and those who are lean and non-diabetic. Although some shared taxa are often cited, there is still no clear consensus on the precise microbial composition that triggers metabolic disorders, and causality between specific microbes and the development of such diseases is yet to be proven in humans. Nevertheless, gastric bypass is most likely the most efficient procedure for reducing body weight and treating T2D. Interestingly, several reports have shown that the gut microbiota is profoundly affected by the procedure. It has been suggested that the consistent postoperative increase in certain bacterial groups such as Proteobacteria, Bacteroidetes and Verrucomicrobia (A. muciniphila) may explain its beneficial impact in gnotobiotic mice. Taken together, these data suggest that specific gut microbes modulate important host biological systems that contribute to the control of energy homoeostasis, glucose metabolism and inflammation in obesity and T2D.

  16. Prevalence of insulin resistance and the metabolic syndrome with alternative definitions of impaired fasting glucose.

    Science.gov (United States)

    Ford, Earl S; Abbasi, Fahim; Reaven, Gerald M

    2005-07-01

    We sought to evaluate the effect of the new definition of impaired fasting glucose (IFG = fasting glucose concentration 100-125 mg/dL among people without diabetes) on the ability to identify insulin resistance, as well as the prevalence of the metabolic syndrome in apparently healthy individuals. From the Stanford General Clinical Research Center data-base, we used data from 230 men and 260 women aged 19-79 years who had had an insulin suppression test to measure insulin resistance. From the Third National Health and Nutrition Examination Survey (1988-1994), we used data from 8814 participants aged > or =20 years to estimate the impact of adopting the new IFG criteria on the prevalence of the metabolic syndrome. Among the 490 participants, the prevalence of IFG increased from 5.5% under the old definition of IFG to 20.4% under the new definition. Using the old definition of IFG, the sensitivity, specificity, and positive predictive value (PPV) of IFG of identifying an individual as being insulin resistant were 10%, 97%, and 63%, respectively. Using the new definition, these parameters were 33%, 88%, and 61%, respectively. If the new IFG criteria were adopted, the prevalence of the metabolic syndrome would increase from 21.8% to 26.3%. The new definition of IFG expands the population with insulin resistance by almost four-fold and could expand the population with the metabolic syndrome by about 20%. The clinical and public health implications of the new IFG definition remain to be elucidated.

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

    Directory of Open Access Journals (Sweden)

    Frederick Wasinski

    2014-01-01

    Full Text Available 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 association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

  18. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

    DEFF Research Database (Denmark)

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki

    2015-01-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled...... were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined...... nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus...

  19. Niclosamide reduces glucagon sensitivity via hepatic PKA inhibition in obese mice: Implications for glucose metabolism improvements in type 2 diabetes

    Science.gov (United States)

    Chowdhury, Md. Kamrul Hasan; Turner, Nigel; Bentley, Nicholas L.; Das, Abhirup; Wu, Lindsay E.; Richani, Dulama; Bustamante, Sonia; Gilchrist, Robert B.; Morris, Margaret J.; Shepherd, Peter R.; Smith, Greg C.

    2017-01-01

    Type 2 diabetes (T2D) is a global pandemic. Currently, the drugs used to treat T2D improve hyperglycemic symptom of the disease but the underlying mechanism causing the high blood glucose levels have not been fully resolved. Recently published data showed that salt form of niclosamide improved glucose metabolism in high fat fed mice via mitochondrial uncoupling. However, based on our previous work we hypothesised that niclosamide might also improve glucose metabolism via inhibition of the glucagon signalling in liver in vivo. In this study, mice were fed either a chow or high fat diet containing two different formulations of niclosamide (niclosamide ethanolamine salt - NENS or niclosamide - Nic) for 10 weeks. We identified both forms of niclosamide significantly improved whole body glucose metabolism without altering total body weight or body composition, energy expenditure or insulin secretion or sensitivity. Our study provides evidence that inhibition of the glucagon signalling pathway contributes to the beneficial effects of niclosamide (NENS or Nic) on whole body glucose metabolism. In conclusion, our results suggest that the niclosamide could be a useful adjunctive therapeutic strategy to treat T2D, as hepatic glucose output is elevated in people with T2D and current drugs do not redress this adequately. PMID:28054648

  20. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    Directory of Open Access Journals (Sweden)

    Zhai Hua-Ling

    2012-01-01

    Full Text Available Abstract Background There