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Sample records for cerebral glucose uptake

  1. 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

    uptake increased disproportionately to cerebral oxygen uptake, and the cerebral oxygen to glucose uptake ratio was 4.2. The accumulated excess glucose uptake during 6 minutes of activation amounted to 2.4 micromol/g. Activation was terminated by closure of the sheltering box. In the postactivation period......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...

  2. 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...

  3. The effects of capillary transit time heterogeneity (CTH on the cerebral uptake of glucose and glucose analogs:Application to FDG and comparison to oxygen uptake.

    Directory of Open Access Journals (Sweden)

    Hugo Angleys

    2016-10-01

    Full Text Available Glucose is the brain’s principal source of ATP, but the extent to which cerebral glucose consumption (CMRglc is coupled with its oxygen consumption (CMRO2 remains unclear. Measurements of the brain’s oxygen-glucose index OGI=CMRO2/CMRglc suggest that its oxygen uptake largely suffices for oxidative phosphorylation. Nevertheless, during functional activation and in some disease states, brain tissue seemingly produces lactate although cerebral blood flow (CBF delivers sufficient oxygen, so-called aerobic glycolysis. OGI measurements, in turn, are method-dependent in that estimates based on glucose analog uptake depend on the so-called lumped constant (LC to arrive at CMRglc. Capillary transit time heterogeneity (CTH, which is believed to change during functional activation and some disease states, affects the extraction efficacy of oxygen from blood. We developed a three-compartment model of glucose extraction to examine whether CTH also affects glucose extraction into brain tissue. We then combined this model with our previous model of oxygen extraction to examine whether differential glucose and oxygen extraction might favor nonoxidative glucose metabolism under certain conditions. Our model predicts that glucose uptake is largely unaffected by changes in its plasma concentration, while changes in CBF and CTH affect glucose and oxygen uptake to different extents. Accordingly, functional hyperemia facilitates glucose uptake more than oxygen uptake, favoring aerobic glycolysis during enhanced energy demands. Applying our model to glucose analogs, we observe that LC depends on physiological state, with a risk of overestimating relative increases in CMRglc during functional activation by as much as 50%.

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

    International Nuclear Information System (INIS)

    Polonsky, K.

    1987-01-01

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

  5. Relationship between local cerebral glucose uptakes, serum prolactin, growth hormone and cortisol levels changes during epilepsy

    International Nuclear Information System (INIS)

    Wang Mingfang; Mao Xianghui; Tang Ganghua; Zhao Jun; Sun Aijun

    2002-01-01

    Objective: To explore the relation of local cerebral FDG uptake value of glucose to the changes of prolactin (PRL), growth hormone (GH) and cortisol levels in serum during epilepsy. Methods: 76 epileptic patients with solitary epileptic focus were examined by 2-deoxy-2-[ 18 F] fluoro-D-glucose ( 18 F-FDG) positron emission tomography (PET) imaging and the FDG uptake value of epileptic foci were measured. Serum PRL, GH and cortisol levels of the patients were determined by radioimmunoassay (RIA) before and after seizures. Results: During ictal studies, all patients showed increased FDG uptake of epileptic foci compared with that in interictal phase. The serum PRL, GH and cortisol levels were significant higher after seizures. The changes of hormone levels correlated significantly with the lengths of seizure free intervals (SFIs) and with the types of seizures. But the variations of hormone levels had no relation with the site and FDG uptake of epileptic foci. In patients with absentia seizures, no significant increase was observed in serum PRL and cortisol levels. The changes of GH were not related with the types of seizures. Also, it was found that changes of hormone levels had significant relations to the lengths of SFIs. Conclusions: Serum PRL, GH and cortisol levels were significantly different before and after seizures. This study suggests that changes of postictal hormone levels correlated significantly with the types of seizures and lengths of SFIs, but the changes of hormone levels are not related with the site and FDG uptake of epileptic foci

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

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    Marsteller, Douglas A.; Barbarich-Marsteller, Nicole C.; Fowler, Joanna S.; Schiffer, Wynne K.; Alexoff, David L.; Rubins, Daniel J.; Dewey, Stephen L.

    2006-01-01

    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-[ 18 F]-fluoro-D-glucose ( 18 FDG) was used to determine the variability of a 50-min brain 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 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 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 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 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. Regional cerebral effects of ketone body infusion with 3-hydroxybutyrate in humans: Reduced glucose uptake, unchanged oxygen consumption and increased blood flow by positron emission tomography. A randomized, controlled trial.

    Science.gov (United States)

    Svart, Mads; Gormsen, Lars C; Hansen, Jakob; Zeidler, Dora; Gejl, Michael; Vang, Kim; Aanerud, Joel; Moeller, Niels

    2018-01-01

    Ketone bodies are neuroprotective in neurological disorders such as epilepsy. We randomly studied nine healthy human subjects twice-with and without continuous infusion of 3-hydroxybutyrate-to define potential underlying mechanisms, assessed regionally (parietal, occipital, temporal, cortical grey, and frontal) by PET scan. During 3-hydroxybutyrate infusions concentrations increased to 5.5±0.4 mmol/l and cerebral glucose utilisation decreased 14%, oxygen consumption remained unchanged, and cerebral blood flow increased 30%. We conclude that acute 3-hydroxybutyrate infusion reduces cerebral glucose uptake and increases cerebral blood flow in all measured brain regions, without detectable effects on cerebral oxygen uptake though oxygen extraction decreased. Increased oxygen supply concomitant with unchanged oxygen utilisation may contribute to the neuroprotective effects of ketone bodies.

  9. Cerebral ammonia uptake and accumulation during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Dalsgaard, Mads K.; Steensberg, Adam

    2005-01-01

    We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebral...... blood flow; n = 5) and the ammonia concentration in the cerebrospinal fluid (CSF; n = 8) at rest and immediately following prolonged exercise either with or without glucose supplementation. There was a net balance of ammonia across the brain at rest and at 30 min of exercise, whereas 3 h of exercise...... exercise with glucose, and further to 16.1 ± 3.3 µM after the placebo trial (P

  10. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  11. Stimulation-induced cerebral glycolytic glucose metabolism

    International Nuclear Information System (INIS)

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

    1989-01-01

    The authors have developed a method to estimate the relative amounts of cerebral oxidative and glycolytic glucose metabolism with sequentially administered radiolabeled fluorode-oxyglucose (FDG) and 6-glucose (GLU). Cerebral FDG metabolite concentration was found to reflect total glucose metabolism. Cerebral GLU metabolite concentration, however, was found to reflect mainly oxidative metabolism, because of significant fraction of the radiolabel was lost through lactate production and diffusion from the brain with glycolysis. The authors applied the method to normal rats, to seizing rats, and to optically stimulated rats. Normal cerebral glucose metabolism was primarily oxidative, but stimulation caused profound increases in glycolysis in activated brain regions

  12. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Richter, Erik

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  13. Normal cerebral FDG uptake during childhood

    International Nuclear Information System (INIS)

    London, Kevin; Howman-Giles, Robert

    2014-01-01

    Current understanding of cerebral FDG uptake during childhood originates from a small number of studies in patients with neurological abnormalities. Our aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children more likely to represent a normal population. We reviewed cerebral FDG PET scans in children up to 16 years of age with suspected/proven extracranial malignancies and the following exclusions: central nervous system metastases, previous malignancies, previous chemotherapy or radiotherapy, development of cerebral metastases during therapy, neurological conditions, taking antiepileptic medication or medications likely to interfere with cerebral metabolism, and general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the cerebellar cortex were analysed using regional SUV max , and the cerebral cortex, basal ganglia, thalamus and cerebellum were analysed using a regional relative uptake analysis in comparison to maximal cortical uptake. Scans from 30 patients (age range 11 months to 16 years, mean age 10 years 5 months) were included. All regions showed increasing SUV max with age. The parietal, occipital, lateral temporal and medial temporal lobes showed lower rates of increasing FDG uptake causing changing patterns of regional FDG uptake during childhood. The cortical regions showing the most intense uptake in early childhood were the parietal and occipital lobes. At approximately 7 years of age these regions had relatively less uptake than the frontal lobes and at approximately 10 years of age these regions had relatively less uptake than the thalamus. Relative FDG uptake in the brain has not reached an adult pattern by 1 year of age, but continues to change up to 16 years of age. The changing pattern is due to different regional rates of increasing cortical FDG uptake, which is less rapid in the parietal, occipital and temporal lobes than in the frontal lobes. (orig.)

  14. Normal cerebral FDG uptake during childhood

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    London, Kevin [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Discipline of Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia); Howman-Giles, Robert [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Disciplines of Imaging and Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia)

    2014-04-15

    Current understanding of cerebral FDG uptake during childhood originates from a small number of studies in patients with neurological abnormalities. Our aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children more likely to represent a normal population. We reviewed cerebral FDG PET scans in children up to 16 years of age with suspected/proven extracranial malignancies and the following exclusions: central nervous system metastases, previous malignancies, previous chemotherapy or radiotherapy, development of cerebral metastases during therapy, neurological conditions, taking antiepileptic medication or medications likely to interfere with cerebral metabolism, and general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the cerebellar cortex were analysed using regional SUV{sub max}, and the cerebral cortex, basal ganglia, thalamus and cerebellum were analysed using a regional relative uptake analysis in comparison to maximal cortical uptake. Scans from 30 patients (age range 11 months to 16 years, mean age 10 years 5 months) were included. All regions showed increasing SUV{sub max} with age. The parietal, occipital, lateral temporal and medial temporal lobes showed lower rates of increasing FDG uptake causing changing patterns of regional FDG uptake during childhood. The cortical regions showing the most intense uptake in early childhood were the parietal and occipital lobes. At approximately 7 years of age these regions had relatively less uptake than the frontal lobes and at approximately 10 years of age these regions had relatively less uptake than the thalamus. Relative FDG uptake in the brain has not reached an adult pattern by 1 year of age, but continues to change up to 16 years of age. The changing pattern is due to different regional rates of increasing cortical FDG uptake, which is less rapid in the parietal, occipital and temporal lobes than in the frontal lobes. (orig.)

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

    DEFF Research Database (Denmark)

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    2012-01-01

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

  16. Increased muscle glucose uptake after exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Ploug, Thorkil; Galbo, Henrik

    1985-01-01

    It has recently been shown that insulin sensitivity of skeletal muscle glucose uptake and glycogen synthesis is increased after a single exercise session. The present study was designed to determine whether insulin is necessary during exercise for development of these changes found after exercise....... Diabetic rats and controls ran on a treadmill and their isolated hindquarters were subsequently perfused at insulin concentrations of 0, 100, and 20,000 microU/ml. Exercise increased insulin sensitivity of glucose uptake and glycogen synthesis equally in diabetic and control rats, but insulin...... responsiveness of glucose uptake was noted only in controls. Analysis of intracellular glucose-6-phosphate, glucose, glycogen synthesis, and glucose transport suggested that the exercise effect on responsiveness might be due to enhancement of glucose disposal. After electrical stimulation of diabetic...

  17. Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

    Science.gov (United States)

    Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

    2017-05-01

    Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of dose: ≤ 0.01 mg/kg) corresponded to an increased glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Mazindol enhances glucose uptake by rat skeletal muscle.

    Science.gov (United States)

    Nagai, K; Nagai, N; Isojima, Y; Itoh, S; Okumura, N; Nakagawa, H

    1994-07-21

    The pharmacological action of mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5-imidazo[2,1-a]isoindo l) was examined by studying its effect on glucose uptake by rat tissues using radiolabelled 2-deoxy-D-glucose. The following results were obtained. (1) The rate constant (Ki) of net tissue 2-deoxy-D-glucose uptake increased in the cerebral cortex (4.7-fold, P mazindol (20 mg/kg). (2) This increase in Ki values of net tissue 2-deoxy-D-glucose uptake was not observed after addition of mazindol to the diet (40 mg/100 g of diet) for 4 days. (3) Mazindol (16.7 ng/ml to 16.7 micrograms/ml) stimulated 2-deoxy-D-glucose transport into sarcolemmal vesicles of the gastrocnemius muscle in vitro (1.6-1.8-fold, P mazindol stimulates glucose transport into skeletal muscles by acting on glucose transporters in the sarcolemmal membrane, and suggest that mazindol may stimulate glucose transport into the brain and heart by a similar mechanism.

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    2016-08-11

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

  1. Skeletal muscle glucose uptake during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Saltin, Bengt

    1988-01-01

    to net lactate uptake. Decreased glucose uptake could not be explained by decreased perfusion. It is concluded that thigh muscle glucose uptake is affected by the size of the total muscle mass engaged in exercise. The decrease in thigh glucose uptake, when arm cranking was added and O2 uptake...

  2. Characteristics of cerebral glucose utilization in dementia

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Matsui, Hiroshige; Meguro, Kenichi; Ueda, Masamichi; Yamada, Kenji; Yamaguchi, Tatsuo; Itoh, Masatoshi; Hatazawa, Jun; Kinomura, Shigeo

    1990-01-01

    To make clear the characteristics of cerebral glucose utilization in dementia, PET studies with 18F-FDG were carried out. Taking the pattern of 18F-FDG utilization, dementia can be subdivided into two types. One type shows a simultaneous and symmetrical reduction glucose utilization in the posterior part of neocortex covering the temporal, parietal and occipital association cortices. This is referred to as type I. Although this type constitutes only about 1/5 of all dementia patients, it is considered the fundamental type of dementia. Aside from this, there is type wherein a simultaneous and symmetrical reduction in glucose utilization of the neocortex. This is type II. It constitutes about 4/5 of all dementia patients which is far more type I. There are no essential difference in the characteristics of cerebral glucose utilization in AD and MID. However, with regards the mean, AD is lower than MID. Various organic defect in neocortex do not correlate with the global reduction in glucose utilization in dementia patients. These results suggest that the reduction in glucose utilization in dementia may be functional disorder. (author)

  3. Mechanisms of glucose uptake in cancer tissue

    International Nuclear Information System (INIS)

    Chung, June Key

    1999-01-01

    Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycolytic pathway. Surrounding macrophages and newly formed granulation tissue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application on FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue

  4. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    Science.gov (United States)

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-11-01

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia-reperfusion (I/R) injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. We found that glucose uptake was remarkably diminished in the myocardium following reperfusion in Sprague-Dawley rats as detected by 18 F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by threefold and GLUT4 translocation remained unchanged compared with those of sham-treated rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated I/R injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, whereas its knockdown increased glucose uptake, suggesting that PDK4 has a role in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial I/R. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in the myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial I/R injury. Copyright © 2017 the American Physiological Society.

  5. Ficus Deltoidea Enhance Glucose Uptake Activity in Cultured Muscle Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Shafii Khamis; Amin Ismail; Muhajir Hamid

    2015-01-01

    Ficus deltoidea or locally known as Mas cotek is one of the common medicinal plants used in Malaysia. Our previous studies showed that this plant have blood glucose lowering effect. Glucose uptake into muscle and adipocytes cells is one of the known mechanisms of blood glucose lowering effect. This study was performed to evaluate the effect of Ficus deltoidea on glucose uptake activity into muscle cells. The cells were incubated with Ficus deltoidea extracts either alone or combination with insulin. Amount of glucose uptake by L6 myotubes was determined using glucose tracer, 2-deoxy-(1- 3 H 1 )-glucose. The results showed that Ficus deltoidea extracts at particular doses enhanced basal or insulin-mediated glucose uptake into muscle cells significantly. Hot aqueous extract enhanced glucose uptake at the low concentration (10 μg/ ml) whereas methanolic extract enhanced glucose uptake at low and high concentrations. Methanolic extract also mimicked insulin activity during enhancing glucose uptake into L^ muscle cells. Glucose uptake activity of Ficus deltoidea could be attributed by the phenolic compound presence in the plant. This study had shown that Ficus deltoidea has the ability to enhance glucose uptake into muscle cells which is partly contributed the antidiabetic activity of this plant. (author)

  6. Cerebral glucose metabolism in Parkinson's disease

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  7. The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ide, Kojiro; Cai, Yan

    2002-01-01

    During and after maximal exercise there is a 15-30 % decrease in the metabolic uptake ratio (O(2)/[glucose + 1/2 lactate]) and a net lactate uptake by the human brain. This study evaluated if this cerebral metabolic uptake ratio is influenced by the intent to exercise, and whether a change could...... be explained by substrates other than glucose and lactate. The arterial-internal jugular venous differences (a-v difference) for O(2), glucose and lactate as well as for glutamate, glutamine, alanine, glycerol and free fatty acids were evaluated in 10 healthy human subjects in response to cycling. However...... to 3.7 +/- 0.2 in the first minutes of the recovery (P

  8. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    , impairment of insulin action on muscle glucose transport and uptake. Thus maximal insulin-stimulated glucose uptake at 12 mM-glucose decreased from 34.8 +/- 1.9 to 11.5 +/- 1.1 mumol/h per g (mean +/- S.E.M., n = 10) during 5 h perfusion. This decrease in glucose uptake was accompanied by a similar change...... in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation....

  9. The intent to exercise influences the cerebral O(2)/carbohydrate uptake ratio in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ide, Kojiro; Cai, Yan

    2002-01-01

    During and after maximal exercise there is a 15-30 % decrease in the metabolic uptake ratio (O(2)/[glucose + 1/2 lactate]) and a net lactate uptake by the human brain. This study evaluated if this cerebral metabolic uptake ratio is influenced by the intent to exercise, and whether a change could......, the a-v difference for the amino acids and glycerol did not change significantly, and there was only a minimal increase in the a-v difference for free fatty acids after maximal exercise. After maximal exercise the metabolic uptake ratio of the brain decreased from 6.1 +/- 0.5 (mean +/- S.E.M.) at rest.......2) in the early recovery (n = 10; P brain are increased out of proportion to O(2) when the brain is activated by exhaustive exercise, and that such metabolic changes are influenced by the will to exercise. We speculate that the uptake ratio...

  10. Pentobarbital inhibits glucose uptake, but not water transport by glucose transporter type 3.

    Science.gov (United States)

    Tomioka, Shigemasa; Kaneko, Miyuki; Nakajo, Nobuyoshi

    2012-08-01

    To understand the mechanisms underlying the neuroprotective efficacy of barbiturates, the effect of pentobarbital on glucose uptake and water transport was determined in Xenopus oocytes expressing glucose transporter type 3 (GLUT3). Pentobarbital induced a 50% concentration-dependent inhibition in glucose uptake, but exerted no effect on water transport by GLUT3. Eadie-Hofstee analysis showed that pentobarbital decreased Vmax significantly, but not Km of GLUT3 for 2-deoxy-D-glucose. Although the protein kinase C (PKC) activator significantly decreased glucose uptake by GLUT3, no additive or synergistic interactions were observed between the PKC activator and pentobarbital. Our results suggest that pentobarbital may play an important role in neuroprotection by inhibition of glucose uptake by GLUT3 by a mechanism involving PKC.

  11. Myocardial glucose uptake and breakdown during adenosine-induced vasodilation.

    Science.gov (United States)

    Turnheim, K; Donath, R; Weissel, M; Kolassa, N

    1976-09-30

    In isolated K+ (16.2 mM)-arrested cat hearts perfused at constant pressure adenosine infusions (0.8 mumoles - min-1 - 100 g-1 for 10 min) caused an increase in myocardial 14C-glucose uptake and release of 14CO2 + H14CO3- AND 14C-lactate simultaneously with a rise in coronary flow. The ratio of the release of 14CO2 + H14CO3- to that of 14C-lactate and the specific activity of lactate in the effuate were not altered. In K+ -arrested hearts perfused with constant volume neither glucose uptake nor glucose breakdown were influenced by 0.8 or 100 mumoles - min-1 - 100 g-1 adenosine with 0.1 - 5 mM glucose in the perfusion medium. It is concluded that adenosine does not affect directly the myocardial glucose carrier system, aerobic or anaerobic glucose breakdown or glycogenolysis, but enhances glucose uptake secondarily by increasing coronary flow. This interpretation is substantiated by the finding that mechanically produced increases in perfusion volume caused similar increases in myocardial glucose uptake as were observed with comparable adenosine-induced coronary flow increments.

  12. Glucose uptake and its effect on gene expression in prochlorococcus.

    Directory of Open Access Journals (Sweden)

    Guadalupe Gómez-Baena

    Full Text Available The marine cyanobacteria Prochlorococcus have been considered photoautotrophic microorganisms, although the utilization of exogenous sugars has never been specifically addressed in them. We studied glucose uptake in different high irradiance- and low irradiance-adapted Prochlorococcus strains, as well as the effect of glucose addition on the expression of several glucose-related genes. Glucose uptake was measured by adding radiolabelled glucose to Prochlorococcus cultures, followed by flow cytometry coupled with cell sorting in order to separate Prochlorococcus cells from bacterial contaminants. Sorted cells were recovered by filtration and their radioactivity measured. The expression, after glucose addition, of several genes (involved in glucose metabolism, and in nitrogen assimilation and its regulation was determined in the low irradiance-adapted Prochlorococcus SS120 strain by semi-quantitative real time RT-PCR, using the rnpB gene as internal control. Our results demonstrate for the first time that the Prochlorococcus strains studied in this work take up glucose at significant rates even at concentrations close to those found in the oceans, and also exclude the possibility of this uptake being carried out by eventual bacterial contaminants, since only Prochlorococcus cells were used for radioactivity measurements. Besides, we show that the expression of a number of genes involved in glucose utilization (namely zwf, gnd and dld, encoding glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and lactate dehydrogenase, respectively is strongly increased upon glucose addition to cultures of the SS120 strain. This fact, taken together with the magnitude of the glucose uptake, clearly indicates the physiological importance of the phenomenon. Given the significant contribution of Prochlorococcus to the global primary production, these findings have strong implications for the understanding of the phytoplankton role in the carbon

  13. 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.

  14. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    OpenAIRE

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

    2008-01-01

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

  15. Exercise, GLUT4, and Skeletal Muscle Glucose Uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hargreaves, Mark

    2013-01-01

    Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter which translocates from intracellular storage depots to the plasma membrane and T-tubules upon...... muscle contraction. Here we discuss the current understanding of how exercise-induced muscle glucose uptake is regulated. We briefly discuss the role of glucose supply and metabolism and concentrate on GLUT4 translocation and the molecular signaling that sets this in motion during muscle contractions....... Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part. While acute regulation of muscle glucose...

  16. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

  17. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Richter, Erik

    1984-01-01

    in the presence of antiserum. 3-O-methylglucose uptake was increased markedly by contractions in fast-twitch red and white fibers that were severely glycogen depleted but not in slow-twitch red fibers that were not glycogen depleted. In hindquarters from ketoacidotic rats perfused exactly as by Berger et al., 3-O...

  18. Ceramide 1-phosphate stimulates glucose uptake in macrophages.

    Science.gov (United States)

    Ouro, Alberto; Arana, Lide; Gangoiti, Patricia; Rivera, Io-Guané; Ordoñez, Marta; Trueba, Miguel; Lankalapalli, Ravi S; Bittman, Robert; Gomez-Muñoz, Antonio

    2013-04-01

    It is well established that ceramide 1-phosphate (C1P) is mitogenic and antiapoptotic, and that it is implicated in the regulation of macrophage migration. These activities require high energy levels to be available in cells. Macrophages obtain most of their energy from glucose. In this work, we demonstrate that C1P enhances glucose uptake in RAW264.7 macrophages. The major glucose transporter involved in this action was found to be GLUT 3, as determined by measuring its translocation from the cytosol to the plasma membrane. C1P-stimulated glucose uptake was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3K) or Akt, also known as protein kinase B (PKB), and by specific siRNAs to silence the genes encoding for these kinases. C1P-stimulated glucose uptake was also inhibited by pertussis toxin (PTX) and by the siRNA that inhibited GLUT 3 expression. C1P increased the affinity of the glucose transporter for its substrate, and enhanced glucose metabolism to produce ATP. The latter action was also inhibited by PI3K- and Akt-selective inhibitors, PTX, or by specific siRNAs to inhibit GLUT 3 expression. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Cerebral glucose metabolism in patients with spasmodic torticollis

    NARCIS (Netherlands)

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

    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

  20. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2016-12-01

    The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

  1. Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina; O'Neill, Hayley M; Kleinert, Maximilian

    2015-01-01

    INTRODUCTION: Members of the interleukin-6 (IL-6) family, IL-6 and ciliary neurotrophic factor (CNTF) have been shown to increase glucose uptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member, leukemia inhibitory factor (LIF), are not well...

  2. 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.

  3. Implications of Resveratrol on Glucose Uptake and Metabolism.

    Science.gov (United States)

    León, David; Uribe, Elena; Zambrano, Angara; Salas, Mónica

    2017-03-07

    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.

  4. Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

    Science.gov (United States)

    Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

    2011-01-01

    Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberrations. At twelve weeks of age, brain uptake of tail vein-injected 3H-2-deoxy glucose in Glut3+/− mice was not different from Glut3+/+ littermates, despite 50% less Glut3 protein expression in the brain. The brain uptake of injected 18F-2-fluoro-2-deoxy glucose was similarly not different from Glut3+/− littermates in the total amount, time course, or brain imaging in the Glut3+/− mice. Glut1 and Glut6 protein expressions evaluated by immunoblots were not affected by the diminished Glut3 expression in the Glut3+/− mice. We conclude that a 50% decrease in Glut3 is not limiting for the uptake of glucose into the mouse brain, since Glut3 haploinsufficiency does not impair brain glucose uptake or utilization. PMID:21316350

  5. Effect of NMDA Receptor Antagonist on Local Cerebral Glucose Metabolic Rate in Focal Cerebral Ischemia

    International Nuclear Information System (INIS)

    Kim, Sang Eun; Hong, Seung Bong; Yoon, Byung Woo

    1995-01-01

    There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuroprotective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (1CGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[14C]glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded 1CGU ratio in 7 and 5 of the 15 regions measured, respectively(most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in 1CCPU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 posttreatment did not significantly increase 1CGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

  6. γ-Oryzanol Enhances Adipocyte Differentiation and Glucose Uptake

    Directory of Open Access Journals (Sweden)

    Chang Hwa Jung

    2015-06-01

    Full Text Available Recent studies show that brown rice improves glucose intolerance and potentially the risk of diabetes, although the underlying molecular mechanisms remain unclear. One of the phytochemicals found in high concentration in brown rice is γ-oryzanol (Orz, a group of ferulic acid esters of phytosterols and triterpene alcohols. Here, we found that Orz stimulated differentiation of 3T3-L1 preadipocytes and increased the protein expression of adipogenic marker genes such as peroxisome proliferator-activated receptor gamma (PPAR-γ and CCAAT/enhanced binding protein alpha (C/EBPα. Moreover, Orz significantly increased the glucose uptake in insulin-resistant cells and translocation of glucose transporter type 4 (GLUT4 from the cytosol to the cell surface. To investigate the mechanism by which Orz stimulated cell differentiation, we examined its effects on cellular signaling of the mammalian target of rapamycin complex 1 (mTORC1, a central mediator of cellular growth and proliferation. The Orz treatment increased mTORC1 kinase activity based on phosphorylation of 70-kDa ribosomal S6 kinase 1 (S6K1. The effect of Orz on adipocyte differentiation was dependent on mTORC1 activity because rapamycin blocks cell differentiation in Orz-treated cells. Collectively, our results indicate that Orz stimulates adipocyte differentiation, enhances glucose uptake, and may be associated with cellular signaling mediated by PPAR-γ and mTORC1.

  7. Moderate Physical Activity is Associated with Cerebral Glucose Metabolism in Adults at Risk for Alzheimer's Disease.

    Science.gov (United States)

    Dougherty, Ryan J; Schultz, Stephanie A; Kirby, Taylor K; Boots, Elizabeth A; Oh, Jennifer M; Edwards, Dorothy; Gallagher, Catherine L; Carlsson, Cynthia M; Bendlin, Barbara B; Asthana, Sanjay; Sager, Mark A; Hermann, Bruce P; Christian, Bradley T; Johnson, Sterling C; Cook, Dane B; Okonkwo, Ozioma C

    2017-01-01

    The objective of this study was to investigate the relationship between accelerometer-measured physical activity (PA) and glucose metabolism in asymptomatic late-middle-aged adults. Ninety-three cognitively healthy late-middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention participated in this cross-sectional study. They underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and wore an accelerometer (ActiGraph GT3X+) to measure free-living PA. Accelerometer data yielded measures of light (LPA), moderate (MPA), and vigorous (VPA) intensity PA. FDG-PET images were scaled to the cerebellum and pons, and cerebral glucose metabolic rate was extracted from specific regions of interest (ROIs) known to be hypometabolic in AD, i.e., hippocampus, posterior cingulate, inferior temporal cortex, and angular gyrus. Regression analyses were utilized to examine the association between PA and glucose metabolism, while adjusting for potential confounds. There were associations between MPA and glucose metabolism in all ROIs examined. In contrast, LPA was not associated with glucose uptake in any ROI and VPA was only associated with hippocampal FDG uptake. Secondary analyses did not reveal associations between sedentary time and glucose metabolism in any of the ROIs. Exploratory voxel-wise analysis identified additional regions where MPA was significantly associated with glucose metabolism including the precuneus, supramarginal gyrus, amygdala, and middle frontal gyrus. These findings suggest that the intensity of PA is an important contributor to neuronal function in a late-middle-aged cohort, with MPA being the most salient. Prospective studies are necessary for fully elucidating the link between midlife engagement in PA and later life development of AD.

  8. Arrhythmia causes lipid accumulation and reduced glucose uptake.

    Science.gov (United States)

    Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

    2015-01-01

    Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  10. Cerebral glucose metabolism on positron emission tomography of children.

    Science.gov (United States)

    Shan, Zuyao Y; Leiker, Andrew J; Onar-Thomas, Arzu; Li, Yimei; Feng, Tianshu; Reddick, Wilburn E; Reutens, David C; Shulkin, Barry L

    2014-05-01

    Establishing the normative range of age-dependent fluorodeoxyglucose (FDG) uptake in the developing brain is necessary for understanding regional quantitative analysis of positron emission tomography (PET) brain images in children and also to provide functional information on brain development. We analyzed head sections of FDG PET/computed tomography (CT) images for 115 patients (5 months to 23 years) without central nervous system disease before treatment, as PET studies are not performed on healthy children owing to ethical considerations and the risk of radiation exposure. We investigated the changes in FDG uptake and established age-associated normative ranges of cerebral FDG. Head sections of FDG PET/CT images were registered to a population-based probabilistic atlas of human cortical structures. Gray matter of 56 brain structures was defined on normalized PET images according to the atlas. To avoid individual and experimental confounding factors, the relative standardized uptake value (SUV) over the cerebellum of each structure was calculated. Relative SUVs were analyzed by ANOVA and modeled using generalized estimating equalization analysis with false discovery rate control. Age and structure were significant factors affecting SUVs. Anatomic proximity had little effect on FDG uptake. Linear and quadratic developmental trajectories were observed on absolute and relative SUVs, respectively. An increase from posterior-to-anterior and superior-to-inferior pattern was observed in both absolute SUV increase rate and relative SUV peak age. The SUV of each structure was modeled with respect to age, and these models can serve as baselines for the quantitative analysis of cerebral FDG-PET images of children. Copyright © 2013 Wiley Periodicals, Inc.

  11. Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans

    DEFF Research Database (Denmark)

    Steensberg, Adam; Fischer, Christian P; Sacchetti, Massimo

    2003-01-01

    The cytokine interleukin (IL)-6 has recently been linked with type 2 diabetes mellitus and has been suggested to affect glucose metabolism. To determine whether acute IL-6 administration affects whole-body glucose kinetics or muscle glucose uptake, 18 healthy young men were assigned to one of three...... and LoIL-6, respectively), followed by a rapid decline (P administration, but were asymptomatic during LoIL-6 administration. In addition, only HiIL-6 elevated (P ... adrenaline (epinephrine). IL-6 infusion, irrespective of dose, did not result in any changes to endogenous glucose production, whole-body glucose disposal or leg- glucose uptake. These data demonstrate that acute IL-6 administration does not impair whole-body glucose disposal, net leg-glucose uptake...

  12. Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats.

    Directory of Open Access Journals (Sweden)

    Anette I Öberg

    Full Text Available BACKGROUND: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin, plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. CONCLUSIONS/SIGNIFICANCE: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.

  13. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  14. 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.

  15. Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.

    Science.gov (United States)

    Gispert, Juan D; Figueiras, Francisca P; Vengeliene, Valentina; Herance, José R; Rojas, Santiago; Spanagel, Rainer

    2017-06-01

    Several [ 18 F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [ 18 F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [ 18 F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [ 18 F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. effect of adrenaline on glucose uptake by the canine large bowel

    African Journals Online (AJOL)

    lower metabolic activity in the colon. From the results we concluded that the colon is involved in glucose homeostasis and that the colonic increase in glucose uptake in response to adrenaline is mediated by alpha and beta adrenergic receptors. KEYWORDS: :Adrenaline, glucose uptake, colon, dog, adrenergic receptors.

  17. Chronic levodopa treatment alters basal and dopamine agonist-stimulated cerebral glucose utilization

    Energy Technology Data Exchange (ETDEWEB)

    Engber, T.M.; Susel, Z.; Kuo, S.; Chase, T.N. (National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA))

    1990-12-01

    The effect of chronic levodopa administration on the functional activity of the basal ganglia and its output regions was evaluated by means of the 2-deoxyglucose (2-DG) autoradiographic technique in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The rates of local cerebral glucose utilization were studied under basal conditions as well as in response to challenge with a selective D1 or D2 dopamine-receptor agonist. Levodopa (100 mg/kg/d, i.p.) was administered for 19 d either continuously via infusion with an osmotic pump or intermittently by twice-daily injections. Following a 3-d washout, glucose utilization was found to be decreased by both levodopa regimens in the nucleus accumbens; intermittent levodopa also decreased glucose utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral habenula. In control (lesioned and treated chronically with saline) rats, the D1 agonist SKF 38393 (5 mg/kg, i.v.) increased 2-DG uptake in the substantia nigra pars reticulata and entopeduncular nucleus ipsilateral to the lesion by 84% and 56%, respectively. Both continuous and intermittent levodopa blunted the SKF 38393-induced elevation in glucose metabolism in the substantia nigra pars reticulata, while intermittent levodopa also attenuated the increase in the entopeduncular nucleus. The D2 agonist quinpirole (0.4 mg/kg, i.v.) did not increase glucose utilization in any brain region in control animals; following intermittent levodopa treatment, however, quinpirole increased 2-DG uptake by 64% in the subthalamic nucleus and by 39% in the deep layers of the superior colliculus on the ipsilateral side.

  18. Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise

    Directory of Open Access Journals (Sweden)

    Rodrigo Martins Pereira

    2017-05-01

    Full Text Available Abstract Glucose uptake is an important phenomenon for cell homeostasis and for organism health. Under resting conditions, skeletal muscle is dependent on insulin to promote glucose uptake.Insulin, after binding to its membrane receptor, triggers a cascade of intracellular reactions culminating in activation of the glucose transporter 4, GLUT4, among other outcomes.This transporter migrates to the plasma membrane and assists in glucose internalization.However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium actto regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulinlevels.Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.

  19. Exercise-stimulated glucose uptake - regulation and implications for glycaemic control

    DEFF Research Database (Denmark)

    Sylow, Lykke; Kleinert, Maximilian; Richter, Erik

    2017-01-01

    Skeletal muscle extracts glucose from the blood to maintain demand for carbohydrates as an energy source during exercise. Such uptake involves complex molecular signalling processes that are distinct from those activated by insulin. Exercise-stimulated glucose uptake is preserved in insulin-resis......-based proteomics indicate that the known regulators of glucose uptake are only the tip of the iceberg. Consequently, many exciting discoveries clearly lie ahead....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-10-01

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

  1. Influence of free fatty acids on glucose uptake in prostate cancer cells

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Divilov, Vadim; Sevak, Kuntalkumar

    2014-01-01

    The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate.......The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate....

  2. Triterpenoids Isolated from Ziziphus jujuba Enhance Glucose Uptake Activity in Skeletal Muscle Cells.

    Science.gov (United States)

    Kawabata, Kyuichi; Kitamura, Kenji; Irie, Kazuhiro; Naruse, Shoma; Matsuura, Tomohiro; Uemae, Tomoyuki; Taira, Shu; Ohigashi, Hajime; Murakami, Shigeru; Takahashi, Masakazu; Kaido, Yoko; Kawakami, Bunsei

    2017-01-01

    Jujube (Ziziphus jujuba Mill.), a traditional folk medicine and functional food in China and South Korea, is known for its beneficial properties, which include anti-cancer, anti-oxidative, and anti-obesity effects. To assess the anti-hyperglycemic effect of jujube in this study, we investigated the glucose uptake-promoting activity of jujube in rat L6 myotubes. After determining that the jujube extract induces muscle glucose uptake, we identified the following active compounds by bioassay-guided fractionation: betulonic acid, betulinic acid, and oleanonic acid. Ursonic acid, known to be present in jujube, was semi-synthesized from ursolic acid and also observed to enhance glucose uptake. These four triterpenic acids induced glucose uptake in a glucose transporter 4-dependent manner. Comparison experiments of jujube fruits from three countries, namely, China, South Korea, and Japan, revealed that Japanese jujube has a higher content of active triterpenoids and is the most potent enhancer of glucose uptake.

  3. Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Parker, Benjamin L; Fritzen, Andreas Mæchel

    2017-01-01

    Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise...

  4. Exercise-induced muscle glucose uptake in mice with graded, muscle-specific GLUT-4 deletion

    Science.gov (United States)

    Howlett, Kirsten F; Andrikopoulos, Sofianos; Proietto, Joseph; Hargreaves, Mark

    2013-01-01

    To investigate the importance of the glucose transporter GLUT-4 for muscle glucose uptake during exercise, transgenic mice with skeletal muscle GLUT-4 expression approximately 30–60% of normal (CON) and approximately 5–10% of normal (KO) were generated using the Cre/Lox system and compared with wild-type (WT) mice during approximately 40 min of treadmill running (KO: 37.7 ± 1.3 min; WT: 40 min; CON: 40 min, P = 0.18). In WT and CON animals, exercise resulted in an overall increase in muscle glucose uptake. More specifically, glucose uptake was increased in red gastrocnemius of WT mice and in the soleus and red gastrocnemius of CON mice. In contrast, the exercise-induced increase in muscle glucose uptake in all muscles was completely abolished in KO mice. Muscle glucose uptake increased during exercise in both red and white quadriceps of WT mice, while the small increases in CON mice were not statistically significant. In KO mice, there was no change at all in quadriceps muscle glucose uptake. No differences in muscle glycogen use during exercise were observed between any of the groups. However, there was a significant increase in plasma glucose levels after exercise in KO mice. The results of this study demonstrated that a reduction in skeletal muscle GLUT-4 expression to approximately 10% of normal levels completely abolished the exercise-induced increase in muscle glucose uptake. PMID:24303141

  5. Thyroid hormone induced oxygen consumption and glucose-uptake in human mononuclear cells

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L E

    1989-01-01

    Cellular oxygen consumption and glucose metabolism were examined in human mononuclear blood cells. The cellular oxygen consumption and glucose uptake were dependent on the number of cells, the temperature and the duration of incubation. Stimulation of the cells by T4 and T3 led to a dose dependen...... thyroid hormones and insulin exerted an additive effect on glucose uptake. Our study indicates a direct intracellular effect of T4 independent of its conversion to T3 and a different mechanism for insulin dependent and thyroid hormone glucose uptake....

  6. Rac1- a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian

    2014-01-01

    understood. The GTPase, Rac1 has, until recently, only been investigated with regards to its involvement in insulin-stimulated glucose uptake. However, we recently found that Rac1 is activated during muscle contraction and exercise in mice and humans. Remarkably, Rac1 seems to be necessary for exercise....../contraction-stimulated glucose uptake in skeletal muscle, since muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake in skeletal muscle. The molecular mechanisms by which Rac1 regulate glucose uptake is presently unknown. However, recent studies link Rac1...... to the actin cytoskeleton, the small GTPase RalA, and/or free radical production, which have previously been shown to be regulators of glucose uptake in muscle. We propose a model in which Rac1 is activated by contraction- and exercise-induced stretch signals and that Rac1 in conjunction with other signaling...

  7. Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake.

    Science.gov (United States)

    Dai, Lei; Hu, Wei Wei; Xia, Lu; Xia, Mi; Yang, Qian

    2016-01-01

    Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes villus atrophy, followed by crypt hyperplasia, reduces the activities of intestinal digestive enzymes, and disrupts the absorption of intestinal nutrients. In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na+-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. In this study, we therefore sought to evaluate the effects of TGEV infection on glucose uptake and SGLT1 and GLUT2 expression. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Moreover, inhibition studies showed that EGFR modulated glucose uptake in control and TGEV infected cells. Finally, high glucose absorption was subsequently found to promote TGEV replication.

  8. Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance.

    Science.gov (United States)

    Hanssen, Mark J W; Wierts, Roel; Hoeks, Joris; Gemmink, Anne; Brans, Boudewijn; Mottaghy, Felix M; Schrauwen, Patrick; van Marken Lichtenbelt, Wouter D

    2015-03-01

    Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation—at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging. We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. www.trialregister.nl NTR3523 FUNDING: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

  9. Methamphetamine inhibits the glucose uptake by human neurons and astrocytes: stabilization by acetyl-L-carnitine.

    Directory of Open Access Journals (Sweden)

    P M Abdul Muneer

    Full Text Available Methamphetamine (METH, an addictive psycho-stimulant drug exerts euphoric effects on users and abusers. It is also known to cause cognitive impairment and neurotoxicity. Here, we hypothesized that METH exposure impairs the glucose uptake and metabolism in human neurons and astrocytes. Deprivation of glucose is expected to cause neurotoxicity and neuronal degeneration due to depletion of energy. We found that METH exposure inhibited the glucose uptake by neurons and astrocytes, in which neurons were more sensitive to METH than astrocytes in primary culture. Adaptability of these cells to fatty acid oxidation as an alternative source of energy during glucose limitation appeared to regulate this differential sensitivity. Decrease in neuronal glucose uptake by METH was associated with reduction of glucose transporter protein-3 (GLUT3. Surprisingly, METH exposure showed biphasic effects on astrocytic glucose uptake, in which 20 µM increased the uptake while 200 µM inhibited glucose uptake. Dual effects of METH on glucose uptake were paralleled to changes in the expression of astrocytic glucose transporter protein-1 (GLUT1. The adaptive nature of astrocyte to mitochondrial β-oxidation of fatty acid appeared to contribute the survival of astrocytes during METH-induced glucose deprivation. This differential adaptive nature of neurons and astrocytes also governed the differential sensitivity to the toxicity of METH in these brain cells. The effect of acetyl-L-carnitine for enhanced production of ATP from fatty oxidation in glucose-free culture condition validated the adaptive nature of neurons and astrocytes. These findings suggest that deprivation of glucose-derived energy may contribute to neurotoxicity of METH abusers.

  10. Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

    International Nuclear Information System (INIS)

    Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B.

    1991-01-01

    Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection

  11. Measurement of regional cerebral glucose utilization in man by positron emission tomography

    International Nuclear Information System (INIS)

    Baron, J.C.

    1986-05-01

    The various methods available for the study of regional cerebral glucose consumption in man by positron emission tomography are described and their applications, limitations and principal physiopathological results are presented [fr

  12. 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

  13. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

    The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  15. Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Lucia Natarelli

    Full Text Available Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG. In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9 and effector caspases (caspase 7 and 3 and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.

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

    Directory of Open Access Journals (Sweden)

    Jae Hyun Park

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

  17. Glucose uptake in rat soleus: effect of acute unloading and subsequent reloading

    International Nuclear Information System (INIS)

    Henriksen, E.J.; Tischler, M.E.

    1988-01-01

    The effect of acutely reduced weight bearing (unloading) on the in vitro uptake of 2-[1,2- 3 H]deoxy-D-glucose was studied in the soleus muscle by tail casting and suspending rats. After just 4 h, the uptake of 2-deoxy-D-glucose fell (-19%, P less than 0.01) and declined further after an additional 20 h of unloading. This diminution at 24 h was associated with slower oxidation of [ 14 C]glucose and incorporation of [ 14 C]glucose into glycogen. Unlike after 1 day, at 3 days of unloading basal uptake of 2-deoxy-D-glucose did not differ from control. Reloading of the soleus after 1 or 3 days of unloading increased uptake of 2-deoxy-D-glucose above control and returned it to normal within 6 h and 4 days, respectively. These effects of unloading and recovery were caused by local changes in the soleus, because the extensor digitorum longus from the same hindlimbs did not display any alterations in uptake of 2-deoxy-D-glucose or metabolism of glucose. This study demonstrates that alterations in contractile activity, brought about by unloading or recovery from unloading, can influence the regulation of glucose transport in the soleus

  18. Glucose uptake in rat soleus: effect of acute unloading and subsequent reloading

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, E.J.; Tischler, M.E.

    1988-04-01

    The effect of acutely reduced weight bearing (unloading) on the in vitro uptake of 2-(1,2-/sup 3/H)deoxy-D-glucose was studied in the soleus muscle by tail casting and suspending rats. After just 4 h, the uptake of 2-deoxy-D-glucose fell (-19%, P less than 0.01) and declined further after an additional 20 h of unloading. This diminution at 24 h was associated with slower oxidation of (/sup 14/C)glucose and incorporation of (/sup 14/C)glucose into glycogen. Unlike after 1 day, at 3 days of unloading basal uptake of 2-deoxy-D-glucose did not differ from control. Reloading of the soleus after 1 or 3 days of unloading increased uptake of 2-deoxy-D-glucose above control and returned it to normal within 6 h and 4 days, respectively. These effects of unloading and recovery were caused by local changes in the soleus, because the extensor digitorum longus from the same hindlimbs did not display any alterations in uptake of 2-deoxy-D-glucose or metabolism of glucose. This study demonstrates that alterations in contractile activity, brought about by unloading or recovery from unloading, can influence the regulation of glucose transport in the soleus.

  19. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

    2002-01-01

    , bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) ...The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure...... glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity....

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Park, Hyun Soo; Lee, Eun Ju; Kim, Yu Kyeong; Kim, Sang Sun

    2007-01-01

    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

  2. Direct effects of FGF21 on glucose uptake in human skeletal muscle

    DEFF Research Database (Denmark)

    Mashili, Fredirick L; Austin, Reginald L; Deshmukh, Atul S

    2011-01-01

    21 were determined in normal glucose tolerant (n = 40) and type 2 diabetic (T2D; n = 40) subjects. We determined whether FGF21 has direct effects on glucose metabolism in cultured myotubes (n = 8) and extensor digitorum longus skeletal muscle. RESULTS: Serum FGF21 levels increased 20% in T2D versus...... and insulin-stimulated glucose uptake in human myotubes, coincident with increased glucose transporter 1 mRNA, and enhanced glucose transporter 1 abundance at the plasma membrane. In isolated extensor digitorum longus muscle, FGF21 potentiated insulin-stimulated glucose transport, without altering...

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  4. Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes

    DEFF Research Database (Denmark)

    Che, Brita Ngum; Oksbjerg, Niels; Hellgren, Lars

    2013-01-01

    ABSTRACT: BACKGROUND: Phytanic acid (PA) is a chlorophyll metabolite with potentials in regulating glucose metabolism, as it is a natural ligand of the peroxisome proliferator-activated receptor (PPAR) that is known to regulate hepatic glucose homeostasis. This study aimed to establish primary...... and tritiated 2-deoxyglucose (2-DOG) was used to measure glucose uptake, in relation to PA and 2-DOG exposure times and also in relation to PA and insulin concentrations. The MIXED procedure model of SAS was used for statistical analysis of data. RESULTS: PA increased glucose uptake by approximately 35...

  5. Increasing exercise intensity reduces heterogeneity of glucose uptake in human skeletal muscles.

    Directory of Open Access Journals (Sweden)

    Ilkka Heinonen

    Full Text Available Proper muscle activation is a key feature of survival in different tasks in daily life as well as sports performance, but can be impaired in elderly and in diseases. Therefore it is also clinically important to better understand the phenomenon that can be elucidated in humans non-invasively by positron emission tomography (PET with measurements of spatial heterogeneity of glucose uptake within and among muscles during exercise. We studied six healthy young men during 35 minutes of cycling at relative intensities of 30% (low, 55% (moderate, and 75% (high of maximal oxygen consumption on three separate days. Glucose uptake in the quadriceps femoris muscle group (QF, the main force producing muscle group in recreational cycling, and its four individual muscles, was directly measured using PET and 18F-fluoro-deoxy-glucose. Within-muscle heterogeneity was determined by calculating the coefficient of variance (CV of glucose uptake in PET image voxels within the muscle of interest, and among-muscles heterogeneity of glucose uptake in QF was expressed as CV of the mean glucose uptake values of its separate muscles. With increasing intensity, within-muscle heterogeneity decreased in the entire QF as well as within its all four individual parts. Among-muscles glucose uptake heterogeneity also decreased with increasing intensity. However, mean glucose uptake was consistently lower and heterogeneity higher in rectus femoris muscle that is known to consist of the highest percentage of fast twitch type II fibers, compared to the other three QF muscles. In conclusion, these results show that in addition to increased contribution of distinct muscle parts, with increases in exercise intensity there is also an enhanced recruitment of muscle fibers within all of the four heads of QF, despite established differences in muscle-part specific fiber type distributions. Glucose uptake heterogeneity may serve as a useful non-invasive tool to elucidate muscle activation

  6. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

    Energy Technology Data Exchange (ETDEWEB)

    Kofoed, Klaus F.; Hove, Jens D.; Freiberg, Jacob; Hoest, Ulla; Kelbaek, Henning [Cardiovascular PET Research Unit, Section 9201, Medical Department B, The Heart Center, Rigshospitalet, University of Copenhagen, Juliane Mariesvej 24, 2100 Copenhagen (Denmark); Holm, Soeren [The Cyclotron and PET Unit, Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, University of Copenhagen (Denmark)

    2002-12-01

    The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity (r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow (r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity. (orig.)

  7. Glucose uptake and growth of glucose-limited chemostat cultures of Aspergillus niger and a disruptant lacking MstA, a high-affinity glucose transporter

    NARCIS (Netherlands)

    Jorgensen, T.R.; vanKuyk, P.A.; Poulsen, B.R.; Ruijter, G.J.G.; Visser, J.; Iversen, J.J.L.

    2007-01-01

    This is a study of high-affinity glucose uptake in Aspergillus niger and the effect of disruption of a high-affinity monosaccharide-transporter gene, mstA. The substrate saturation constant (K-s) of a reference strain was about 15 mu M in glucose-limited chemostat culture. Disruption of mstA

  8. Metabolism and acetylation contribute to leucine-mediated inhibition of cardiac glucose uptake.

    Science.gov (United States)

    Renguet, Edith; Ginion, Audrey; Gélinas, Roselle; Bultot, Laurent; Auquier, Julien; Robillard Frayne, Isabelle; Daneault, Caroline; Vanoverschelde, Jean-Louis; Des Rosiers, Christine; Hue, Louis; Horman, Sandrine; Beauloye, Christophe; Bertrand, Luc

    2017-08-01

    High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells have suggested that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts. Although leucine activated mTOR/p70S6K, the mTOR inhibitor rapamycin did not prevent leucine's inhibitory action on glucose uptake, ruling out the contribution of the insulin-negative feedback loop. α-Ketoisocaproate, the first metabolite of leucine catabolism, mimicked leucine's effect on glucose uptake. Incubation of cardiomyocytes with [ 13 C]leucine ascertained its metabolism to ketone bodies (KBs), which had a similar negative impact on insulin-stimulated glucose transport. Both leucine and KBs reduced glucose uptake by affecting translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Finally, we found that leucine elevated the global protein acetylation level. Pharmacological inhibition of lysine acetyltransferases counteracted this increase in protein acetylation and prevented leucine's inhibitory action on both glucose uptake and GLUT4 translocation. Taken together, these results indicate that leucine metabolism into KBs contributes to inhibition of cardiac glucose uptake by hampering the translocation of GLUT4-containing vesicles via acetylation. They offer new insights into the establishment of insulin resistance in the heart. NEW & NOTEWORTHY Catabolism of the branched-chain amino acid leucine into ketone bodies efficiently inhibits cardiac glucose uptake through decreased translocation of glucose transporter 4 to the plasma membrane. Leucine increases protein acetylation. Pharmacological inhibition of acetylation

  9. Root uptake of 14C-labeled glucose by radish seedling

    International Nuclear Information System (INIS)

    Momoshima, Noriyuki; Tjahaja, P.I.; Takashima, Yoshimasa

    1991-01-01

    Assimilation of simple carbohydrate by root uptake was examined by cultivation of radish seedling in a solution containing glucose labeled with 14 C. Activity in plant increased rapidly and showed 10 to 30 percent of that in the culture solution within 1 h. Activity in plant, however, did not exceed that in the solution after 11 days cultivation, indicating assimilaiton of glucose by root uptake is negligible under photosynthesis is active. (author)

  10. Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia.

    Science.gov (United States)

    Xu, Lili; Hu, Zhiyong; Shen, Jianjun; McQuillan, Patrick M

    2015-04-01

    Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated. There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (pGinkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Glucose uptake in muscle cell cultures from endurance-trained men.

    Science.gov (United States)

    Berggren, Jason R; Tanner, Charles J; Koves, Timothy R; Muoio, Deborah M; Houmard, Joseph A

    2005-04-01

    To examine noninsulin- (basal) and insulin-mediated glucose uptake in human skeletal muscle cells from endurance-trained and sedentary individuals. Muscle biopsies (vastus lateralis) were obtained from competitive, endurance-trained athletes (N=12; VO2peak 64.9+/-2.3 mL.kg-1.min-1) and their sedentary counterparts (N=8; VO2peak 51.8+/-2.2 mL.kg-1.min-1), and isolated satellite cells allowed to proceed to myotubes. The myotubes exhibited a dose response for glucose uptake with increasing insulin concentrations; maximal glucose uptake was approximately 1.5-fold over basal. In relation to exercise training status, basal glucose uptake was significantly (PetaM, although the relative increase in insulin-mediated glucose uptake (fold increase over basal) did not differ between the sedentary and endurance-trained cells. These data suggest that cultured skeletal muscle cells from endurance-trained athletes may differ in respect to basal glucose uptake.

  12. Glucose uptake and growth of glucose-limited chemostat cultures of Aspergillus niger and a disruptant lacking MstA, a high-affinity glucose transporter

    DEFF Research Database (Denmark)

    Jørgensen, Thomas R; vanKuyk, Patricia A; Poulsen, Bjarne R

    2007-01-01

    This is a study of high-affinity glucose uptake in Aspergillus niger and the effect of disruption of a high-affinity monosaccharide-transporter gene, mstA. The substrate saturation constant (K(s)) of a reference strain was about 15 microM in glucose-limited chemostat culture. Disruption of mst......-affinity uptake system of A. niger. The mstA disruptant and a reference strain were cultivated in glucose-limited chemostat cultures at low, intermediate and high dilution rate (D=0.07 h(-1), 0.14 h(-1) and 0.20 h(-1)). Mycelium harvested from steady-state cultures was subjected to glucose uptake assays...

  13. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    International Nuclear Information System (INIS)

    Hingorani, V.; Brecher, P.

    1987-01-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6- 14 C]glucose or [1- 14 C]oleic acid and the incorporation of radioactivity into 14 CO 2 , lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO 2 was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to 14 CO 2 was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO 2 and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously

  14. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine.

    Science.gov (United States)

    Stumvoll, M; Chintalapudi, U; Perriello, G; Welle, S; Gutierrez, O; Gerich, J

    1995-11-01

    Despite ample evidence that the kidney can both produce and use appreciable amounts of glucose, the human kidney is generally regarded as playing a minor role in glucose homeostasis. This view is based on measurements of arteriorenal vein glucose concentrations indicating little or no net release of glucose. However, inferences from net balance measurements do not take into consideration the simultaneous release and uptake of glucose by the kidney. Therefore, to assess the contribution of release and uptake of glucose by the human kidney to overall entry and removal of plasma glucose, we used a combination of balance and isotope techniques to measure renal glucose net balance, fractional extraction, uptake and release as well as overall plasma glucose appearance and disposal in 10 normal volunteers under basal postabsorptive conditions and during a 3-h epinephrine infusion. In the basal postabsorptive state, there was small but significant net output of glucose by the kidney (66 +/- 22 mumol.min-1, P = 0.016). However, since renal glucose fractional extraction averaged 2.9 +/- 0.3%, there was considerable renal glucose uptake (2.3 +/- 0.2 mumol.kg-1.min-1) which accounted for 20.2 +/- 1.7% of systemic glucose disposal (11.4 +/- 0.5 mumol.kg-1.min-1). Renal glucose release (3.2 +/- 0.2 mumol.kg-1.min-1) accounted for 27.8 +/- 2.1% of systemic glucose appearance (11.4 +/- 0.5 mumol.kg-1.min-1). Epinephrine infusion, which increased plasma epinephrine to levels observed during hypoglycemia (3722 +/- 453 pmol/liter) increased renal glucose release nearly twofold (5.2 +/- 0.5 vs 2.8 +/- 0.1 mol.kg-1.min-1, P = 0.01) so that at the end of the infusion, renal glucose release accounted for 40.3 +/- 5.5% of systemic glucose appearance and essentially all of the increase in systemic glucose appearance. These observations suggest an important role for the human kidney in glucose homeostasis.

  15. Effect of adrenaline on glucose uptake by the canine larger bowel ...

    African Journals Online (AJOL)

    The effect of adrenaline on the glucose uptake by the large intestine was studied on a fasted, anaesthetized dog. A vein draining a segment of the colon was cannulated for blood flow measurement and blood samples were obtained for measurement of glucose content of the arterial and venous blood from the colonic ...

  16. Estimation of insulin secretion, glucose uptake by tissues, and liver handling of glucose using a mathematical model of glucose-insulin homeostasis in lean and obese mice.

    Science.gov (United States)

    Brenner, Michael; Abadi, Sakineh Esmaeili Mohsen; Balouchzadeh, Ramin; Lee, H Felix; Ko, Hoo Sang; Johns, Michael; Malik, Nehal; Lee, Joshua J; Kwon, Guim

    2017-06-01

    Destruction of the insulin-producing β-cells is the key determinant of diabetes mellitus regardless of their types. Due to their anatomical location within the islets of Langerhans scattered throughout the pancreas, it is difficult to monitor β-cell function and mass clinically. To this end, we propose to use a mathematical model of glucose-insulin homeostasis to estimate insulin secretion, glucose uptake by tissues, and hepatic handling of glucose. We applied the mathematical model by Lombarte et al. (2013) to compare various rate constants representing glucose-insulin homeostasis between lean (11% fat)- and high fat diet (HFD; 45% fat)-fed mice. Mice fed HFD (n = 12) for 3 months showed significantly higher body weights (49.97 ± 0.52 g vs. 29.86 ± 0.46 g), fasting blood glucose levels (213.08 ± 10.35 mg/dl vs. 121.91 ± 2.26 mg/dl), and glucose intolerance compared to mice fed lean diet (n = 12). Mice were injected with 1 g/kg glucose intraperitoneally and blood glucose levels were measured at various intervals for 120 min. We performed simulation using Arena™ software based on the mathematical model and estimated the rate constants (9 parameters) for various terms in the differential equations using OptQuest™. The simulated data fit accurately to the observed data for both lean and obese mice, validating the use of the mathematical model in mice at different stages of diabetes progression. Among 9 parameters, 5 parameters including basal insulin, k 2 (rate constant for insulin-dependent glucose uptake to tissues), k 3 (rate constant for insulin-independent glucose uptake to tissues), k 4 (rate constant for liver glucose transfer), and I pi (rate constant for insulin concentration where liver switches from glucose release to uptake) were significantly different between lean- and HFD-fed mice. Basal blood insulin levels, k 3 , and I pi were significantly elevated but k 2 and k 4 were reduced in mice fed a HFD compared to those fed a lean diet. Non

  17. Effects of blood glucose level on FDG uptake by liver: a FDG-PET/CT study

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, Kazuo, E-mail: kkubota@cpost.plala.or.j [Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, Tokyo 162-8655 (Japan); Watanabe, Hiroshige; Murata, Yuji [Department of Radiology, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519 (Japan); Yukihiro, Masashi; Ito, Kimiteru; Morooka, Miyako; Minamimoto, Ryogo [Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, Tokyo 162-8655 (Japan); Hori, Ai [Department of Epidemiology and International Health, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655 (Japan); Shibuya, Hitoshi [Department of Radiology, Faculty of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519 (Japan)

    2011-04-15

    In FDG-PET for abdominal malignancy, the liver may be assumed as an internal standard for grading abnormal FDG uptake both in early images and in delayed images. However, physiological variables of FDG uptake by the liver, especially the effects of blood glucose level, have not yet been elucidated. Methods: FDG-PET studies of 70 patients examined at 50 to 70 min after injection (60{+-}10 min: early images) and of 68 patients examined at 80 to 100 min after injection (90{+-}10 min: delayed images) were analyzed for liver FDG uptake. Patients having lesions in the liver, spleen and pancreas; patients having bulk tumor in other areas; and patients early after chemotherapy or radiotherapy were excluded; also, patients with blood glucose level over 125 mg/dl were excluded. Results: Mean standardized uptake value (SUV) of the liver, blood glucose level and sex showed no significant differences between early images and delayed images. However, liver SUV in the delayed image showed a larger variation than that in the early image and showed significant correlation to blood glucose level. The partial correlation coefficient between liver SUV and blood glucose level in the delayed image with adjustment for sex and age was 0.73 (P<.0001). Multivariate regression coefficient (95% confidence interval) of blood glucose was 0.017 (0.013-0.021). Conclusion: Blood glucose level is an important factor affecting the normal liver FDG uptake in nondiabetic patients. In the case of higher glucose level, liver FDG uptake is elevated especially in the delayed image. This may be due to the fact that the liver is the key organ responsible for glucose metabolism through gluconeogenesis and glycogen storage.

  18. Impact of assimilable nitrogen availability in glucose uptake kinetics in Saccharomyces cerevisiae during alcoholic fermentation.

    Science.gov (United States)

    Palma, Margarida; Madeira, Sara Cordeiro; Mendes-Ferreira, Ana; Sá-Correia, Isabel

    2012-07-30

    The expression and activity of the different Saccharomyces cerevisiae hexose uptake systems (Hxt) and the kinetics of glucose uptake are considered essential to industrial alcoholic fermentation performance. However, the dynamics of glucose uptake kinetics during the different stages of fermentation, depending on glucose and nitrogen availability, is very poorly characterized. The objective of the present work was to examine thoroughly the alterations occurring in glucose uptake kinetics during alcoholic fermentation, by the wine strain S. cerevisiae PYCC 4072, of a synthetic grape juice basal medium with either a limiting or non-limiting initial nitrogen concentration and following nitrogen supplementation of the nitrogen-depleted sluggish fermentation. Independently of the initial concentration of the nitrogen source, glucose transport capacity is maximal during the early stages of fermentation and presumably sustained by the low-affinity and high-capacity glucose transporter Hxt1p. During nitrogen-limited sluggish fermentation, glucose uptake capacity was reduced to approximately 20% of its initial values (Vmax = 4.9 ± 0.8 compared to 21.9 ± 1.2 μmol h⁻¹ 10⁻⁸ cells), being presumably sustained by the low-affinity glucose transporter Hxt3p (considering the calculated Km = 39.2 ± 8.6 mM). The supplementation of the sluggish fermentation broth with ammonium led to the increase of glucose transport capacity associated to the expression of different glucose uptake systems with low and high affinities for glucose (Km = 58.2 ± 9.1 and 2.7 ± 0.4 mM). A biclustering analysis carried out using microarray data, previously obtained for this yeast strain transcriptional response to equivalent fermentation conditions, indicates that the activation of the expression of genes encoding the glucose transporters Hxt2p (during the transition period to active fermentation) and Hxt3p, Hxt4p, Hxt6p and Hxt7p (during the period of

  19. Rac1 Is a Novel Regulator of Contraction-Stimulated Glucose Uptake in Skeletal Muscle

    Science.gov (United States)

    Sylow, Lykke; Jensen, Thomas E.; Kleinert, Maximilian; Mouatt, Joshua R.; Maarbjerg, Stine J.; Jeppesen, Jacob; Prats, Clara; Chiu, Tim T.; Boguslavsky, Shlomit; Klip, Amira; Schjerling, Peter; Richter, Erik A.

    2013-01-01

    In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (∼60–100%) and humans (∼40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20–58% in extensor digitorum longus (EDL; P Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake. PMID:23274900

  20. Ability of higenamine and related compounds to enhance glucose uptake in L6 cells.

    Science.gov (United States)

    Kato, Eisuke; Kimura, Shunsuke; Kawabata, Jun

    2017-12-15

    β2-Adrenergic receptor (β2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has β2AR agonist activity, but the involvement of each functional groups in β2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through β2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 4'-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Wortmannin inhibits both insulin- and contraction-stimulated glucose uptake and transport in rat skeletal muscle

    DEFF Research Database (Denmark)

    Wojtaszewski, Jørgen; Hansen, B F; Ursø, Birgitte

    1996-01-01

    stimulation but was unaffected by contractions. In addition, the insulin-stimulated PI 3-kinase activity and muscle glucose uptake and transport in individual muscles were dose-dependently inhibited by wortmannin with one-half maximal inhibition values of approximately 10 nM and total inhibition at 1 micro......The role of phosphatidylinositol (PI) 3-kinase for insulin- and contraction-stimulated muscle glucose transport was investigated in rat skeletal muscle perfused with a cell-free perfusate. The insulin receptor substrate-1-associated PI 3-kinase activity was increased sixfold upon insulin......-stimulated glucose uptake but also decreased the contractility. In conclusion, inhibition of PI 3-kinase with wortmannin in skeletal muscle coincides with inhibition of insulin-stimulated glucose uptake and transport. Furthermore, in contrast to recent findings in incubated muscle, wortmannin also inhibited...

  2. Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke; Jensen, Thomas Elbenhardt; Kleinert, Maximilian

    2013-01-01

    In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates...... contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (~60-100%) and humans (~40......%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20-58% in extensor digitorum longus (EDL; P

  3. Limited effects of exogenous glucose during severe hypoxia and a lack of hypoxia-stimulated glucose uptake in isolated rainbow trout cardiac muscle

    DEFF Research Database (Denmark)

    Becker, Tracy A.; DellaValle, Brian; Gesser, Hans

    2013-01-01

    by exogenous glucose. However, glucose did attenuate the fall in twitch force during severe hypoxia. Glucose uptake was assayed in non-contracting ventricle strips using 2-[(3)H] deoxy-d-glucose (2-DG) under aerobic and hypoxic conditions, at different incubation temperatures and with different inhibitors...

  4. Rhein inhibits glucose uptake in Ehrlich ascites tumor cells by alteration of membrane-associated functions.

    Science.gov (United States)

    Castiglione, S; Fanciulli, M; Bruno, T; Evangelista, M; Del Carlo, C; Paggi, M G; Chersi, A; Floridi, A

    1993-06-01

    Rhein (RH), 4,5 dihydroxyanthraquinone-2-carboxylic acid, is known to inhibit the glycolysis of neoplastic cells by impairing glucose uptake. In order to establish whether this might be due to a selective interaction of the carrier with the drug or to functional modifications of the cell membrane, the effect of RH on glucose uptake in Ehrlich ascites tumor cells has been investigated. RH strongly inhibits the uptake of both 2-deoxyglucose and 3-O-methylglucose, so the reduced influx therefore cannot be ascribed to an effect on glucose phosphorylation. The inhibition of glucose transport does not depend on a reduction of the number of the carriers as indicated by the inability of the drug to interfere with the synthesis of the transporter. Moreover, the extent of total binding of cytochalasin B, as well as the fact that glucose specificity is not altered, indicate that the intrinsic activity of the glucose carrier is not affected. We therefore conclude that the inhibition of glucose uptake must be ascribed to an interaction of the drug with cell membranes that results in an alteration of membrane-associated functions.

  5. Glucose tolerance and myocardial F-18 fluorodeoxyglucose uptake in normal regions in coronary heart disease patients

    International Nuclear Information System (INIS)

    Hasegawa, Shinji; Kusuoka, Hideo; Uehara, Toshiisa; Yamaguchi, Hitoshi; Hori, Masatsugu; Nishimura, Tsunehiko

    1998-01-01

    To elucidate the relation between glucose tolerance and myocardial uptake of F-18 fluorodeoxyglucose (FDG), FDG-PET with 75 g oral glucose loading was performed on 43 coronary artery disease patients (twice in 2 patients). The patients were divided into 4 groups based on the blood glucose level (BS) and the insulinogenic index (II): group 1, normal (n=9); group 2, impaired glucose tolerance (IGT, n=12); group 3, mild diabetes mellitus (DM) (II>0.4, n=12); and group 4, severe DM (II≤0.4, n=12). Percent (%) dose uptake of FDG in the normal regions of the myocardium was not significantly different in groups 1, 2, and 3, but it was much lower in group 4 than in groups 1 and 2. In groups 2, 3, and 4, % dose uptake showed a definite negative correlation with BS 60 min after glucose loading (r=-0.450, p<0.05), and a close positive correlation with II (r=0.363, p<0.05). These findings indicate that myocardial FDG uptake in normal regions is not greatly impaired in patients with IGT or mild DM. Myocardial viability can be assessed by oral glucose loading in patients with IGT and mild DM as well as in patients with normal glucose tolerance. (author)

  6. Change of blood glucose level and its possible mechanism in patients with cerebral stroke

    International Nuclear Information System (INIS)

    Chen Weizhen; Zhang Yong; Zhang Zikang; Mo Congjian

    2003-01-01

    To study the mechanism of the change of blood glucose levels in patients with cerebral stroke, the levels of blood glucose, cortisol, glucogen, insulin, growth hormone, triiodothyronine (T 3 ), thyroxine (T 4 ) and adrenocorticotropic hormone (ACTH) were dynamically measured in 90 patients with cerebral stroke. The circumstances of brain middle line movement, lateral ventricle oppression and entrance brain ventricle of burst hematoma of the patients were examines by CT scan. The total incidence of hyperglycemia in the patients was 42.22%. The blood glucose level was positively related to the cortisol and glucogen levels, and negatively related to the T 3 level. The changed level of blood glucose and its related hormones both returned to normal range in 10 days. Both the ACTH level and the rate of cerebral pathological change in hyperglycemia group were significantly higher than that in normoglycemia and control groups. The rate of cerebral pathological change in elevated ACTH level group was higher than that in normal ACTH level group. The mechanism of hyperglycemia in the patients with cerebral stroke might be related to the stimulation of the hypothalamus, which may induce the discharge of ACTH and glucagon releasing factor, and to that the level of cortisol and glucagon increased, the level of T 3 decreased

  7. Competition between pentoses and glucose during uptake and catabolism in recombinant Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Subtil Thorsten

    2012-03-01

    Full Text Available Abstract Background In mixed sugar fermentations with recombinant Saccharomyces cerevisiae strains able to ferment D-xylose and L-arabinose the pentose sugars are normally only utilized after depletion of D-glucose. This has been attributed to competitive inhibition of pentose uptake by D-glucose as pentose sugars are taken up into yeast cells by individual members of the yeast hexose transporter family. We wanted to investigate whether D-glucose inhibits pentose utilization only by blocking its uptake or also by interfering with its further metabolism. Results To distinguish between inhibitory effects of D-glucose on pentose uptake and pentose catabolism, maltose was used as an alternative carbon source in maltose-pentose co-consumption experiments. Maltose is taken up by a specific maltose transport system and hydrolyzed only intracellularly into two D-glucose molecules. Pentose consumption decreased by about 20 - 30% during the simultaneous utilization of maltose indicating that hexose catabolism can impede pentose utilization. To test whether intracellular D-glucose might impair pentose utilization, hexo-/glucokinase deletion mutants were constructed. Those mutants are known to accumulate intracellular D-glucose when incubated with maltose. However, pentose utilization was not effected in the presence of maltose. Addition of increasing concentrations of D-glucose to the hexo-/glucokinase mutants finally completely blocked D-xylose as well as L-arabinose consumption, indicating a pronounced inhibitory effect of D-glucose on pentose uptake. Nevertheless, constitutive overexpression of pentose-transporting hexose transporters like Hxt7 and Gal2 could improve pentose consumption in the presence of D-glucose. Conclusion Our results confirm that D-glucose impairs the simultaneous utilization of pentoses mainly due to inhibition of pentose uptake. Whereas intracellular D-glucose does not seem to have an inhibitory effect on pentose utilization

  8. Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul S

    2016-01-01

    transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle.......Skeletal muscle is the largest tissues in the human body and is considered the primary target for insulin-stimulated glucose disposal. In skeletal muscle, binding of the insulin to insulin receptor (IR) initiates a signaling cascade that results in the translocation of the insulin-sensitive glucose...

  9. Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT

    International Nuclear Information System (INIS)

    Büsing, Karen A.; Schönberg, Stefan O.; Brade, Joachim; Wasser, Klaus

    2013-01-01

    Introduction: Chronically altered glucose metabolism interferes with 18 F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in 18 F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on 18 F-FDG uptake in tumors and biodistribution in normal organ tissues. Methods: 18 F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index > 25. The maximum standardized uptake value (SUV max ) of normal organs and the main tumor site was measured. Differences in SUV max in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance. Results: Increased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUV max in muscle cells and fat, whereas the mean cerebral SUV max was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity. Conclusions: Changes in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases

  10. Glucose production and gluconeogenesis in adults with cerebral malaria

    NARCIS (Netherlands)

    van Thien, H.; Ackermans, M. T.; Dekker, E.; Thanh Chien, V. O.; Le, T.; Endert, E.; Kager, P. A.; Romijn, J. A.; Sauerwein, H. P.

    2001-01-01

    Hypoglycaemia is an important complication in severe malaria, ascribed to an inhibition of gluconeogenesis. However, the only data available suggested that in severe malaria, total glucose production is increased. We measured glucose production and gluconeogenesis after an overnight fast in all

  11. Screening for Bioactive Metabolites in Plant Extracts Modulating Glucose Uptake and Fat Accumulation

    Directory of Open Access Journals (Sweden)

    Rime B. El-Houri

    2014-01-01

    Full Text Available Dichloromethane and methanol extracts of seven different food and medicinal plants were tested in a screening platform for identification of extracts with potential bioactivity related to insulin-dependent glucose uptake and fat accumulation. The screening platform included a series of in vitro bioassays, peroxisome proliferator-activated receptor (PPAR γ-mediated transactivation, adipocyte differentiation of 3T3-L1 cell cultures, and glucose uptake in both 3T3-L1 adipocytes and primary porcine myotubes, as well as one in vivo bioassay, fat accumulation in the nematode Caenorhabditis elegans. We found that dichloromethane extracts of aerial parts of golden root (Rhodiola rosea and common elder (Sambucus nigra as well as the dichloromethane extracts of thyme (Thymus vulgaris and carrot (Daucus carota were able to stimulate insulin-dependent glucose uptake in both adipocytes and myotubes while weekly activating PPARγ without promoting adipocyte differentiation. In addition, these extracts were able to decrease fat accumulation in C. elegans. Methanol extracts of summer savory (Satureja hortensis, common elder, and broccoli (Brassica oleracea enhanced glucose uptake in myotubes but were not able to activate PPARγ, indicating a PPARγ-independent effect on glucose uptake.

  12. Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

    OpenAIRE

    Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

    1987-01-01

    The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years ...

  13. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans

    International Nuclear Information System (INIS)

    Baron, A.D.; Brechtel, G.; Wallace, P.; Edelman, S.V.

    1988-01-01

    In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively

  14. Modulation of glucose uptake in adipose tissue by nitric oxide ...

    Indian Academy of Sciences (India)

    Madhu

    Karnieli E, Barzilai A, Rafaeloff R and Armoni M 1986 Distribution of glucose transporters in membrane fractions isolated from human adipose cells; relative to cell size; J. Clin. Invest. 78. 1051–1055. Li J, Hu X, Selvakumar P, Russell R R, Cushman S W, Holman. G D and Young L H 2004 Role of the nitric oxide pathway in.

  15. Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice

    DEFF Research Database (Denmark)

    Maarbjerg, Stine Just; Jørgensen, Sebastian Beck; Rose, Adam John

    2009-01-01

    Some studies suggest that the 5'-AMP-activated protein kinase (AMPK) is important in regulating muscle glucose uptake in response to intense electrically stimulated contractions. However, it is unknown if AMPK regulates muscle glucose uptake during in vivo exercise. We studied this in male and fe...... signaling is not essential in regulating glucose uptake in mouse skeletal muscle during treadmill exercise and that other unknown mechanisms play a central role. Key words: exercise, glucose uptake, AMPK.......-KD mouse. Muscle glucose clearance was measured using [3H]-2-deoxy-glucose as tracer. In wildtype mice glucose clearance was increased at 30% and 70% of maximal running speed by 40% and 350% in the quadriceps muscle, and by 120% and 380% in gastrocnemius muscle, respectively. Glucose clearance...

  16. Effects of insulin on glucose uptake and leg blood flow in patients with sickle cell disease and normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Serne, EH; Bakker, SJL; van Eps, WS; Donker, AJM; Gans, ROB

    The hemodynamic concept of insulin resistance assumes that vasodilatory effects of insulin determine glucose uptake. Sickle cell disease (SCD) is characterized by microangiopathy and microvascular occlusion. Therefore, we hypothesized that patients with SCD have a reduced insulin-mediated glucose

  17. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

  18. Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [3-3H]glucose studies in healthy subjects

    International Nuclear Information System (INIS)

    Schmitz, O.; Arnfred, J.; Hother Nielsen, O.; Beck-Nielsen, H.; Oerskov, H.

    1986-01-01

    To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45mU/kg · min or in identical amounts in pulses of 1 1 / 2 to 2 1 / 4 min followed by intervals of 10 1 / 2 to 9 3 / 4 min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270-294 min: 8.7±0.7 vs 6.8±0.9 ml/kg · min, P 3 H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion. (author)

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  20. Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise

    DEFF Research Database (Denmark)

    Madsen, P L; Sperling, B K; Warming, T

    1993-01-01

    . To investigate this controversy, we applied the Kety-Schmidt technique to measure the global average levels of CBF and cerebral metabolic rate of oxygen (CMRO2) during rest and dynamic exercise. Simultaneously with the determination of CBF and CMRO2, we used TCD to determine mean maximal flow velocity...

  1. Contraction-mediated glucose uptake is increased in men with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Skov-Jensen, Camilla; Skovbro, Mette; Flint, Anne

    2007-01-01

    Exercise superimposed on insulin stimulation is shown to increase muscle glucose metabolism and these two stimuli have synergistic effects. The objective of this study was to investigate glucose infusion rates (GIR) in groups with a wide variation in terms of insulin sensitivity during insulin...

  2. 14 C-Glucose uptake studies in the red rot toxin treated sugarcane ...

    African Journals Online (AJOL)

    Fungal toxins cause serious damage to the cellular functions of host tissue. In the present report the toxin extracted from Colletotrichum falcatum Went was partially purified and treatments were given to the callus of susceptible sugarcane callus variety CoC 671. The influence on 14C-glucose uptake and its further utilization ...

  3. effects of caffeine and ethanolic extract of kolanut on glucose uptake ...

    African Journals Online (AJOL)

    Daniel Owu

    Summary: The study investigated the effects of caffeine and ethanolic extract of kolanut (EEK) on glucose uptake in the canine hindlimb at rest and during contraction. Thirty male anaesthetized Mongrel dogs (11. - 13kg) were divided into six groups (5dogs/group). Caffeine (6mg/kg), EEK (5mg/kg), or normal saline. (control) ...

  4. Effect of guava (Psidium guajava L.) leaf extract on glucose uptake in rat hepatocytes.

    Science.gov (United States)

    Cheng, Fang-Chi; Shen, Szu-Chuan; Wu, James Swi-Bea

    2009-06-01

    People in oriental countries, including Japan and Taiwan, boil guava leaves (Psidium guajava L.) in water and drink the extract as a folk medicine for diabetes. The present study investigated the enhancement of aqueous guava leaf extract on glucose uptake in rat clone 9 hepatocytes and searched for the active compound. The extract was eluted with MeOH-H(2)O solutions through Diaion, Sephadex, and MCI-gel columns to separate into fractions with different polarities. The uptake test of 2-[1-(14)C] deoxy-D-glucose in rat clone 9 hepatocytes was performed to evaluate the hypoglycemic effect of these fractions. The active compound was identified by nuclear magnetic resonance analysis and high-performance liquid chromatography (HPLC). The results revealed that phenolics are the principal component of the extract, that high polarity fractions of the guava leaf extract are enhancers to glucose uptake in rat clone 9 hepatocytes, and that quercetin is the major active compound. We suggest that quercetin in the aqueous extract of guava leaves promotes glucose uptake in liver cells, and contributes to the alleviation of hypoglycemia in diabetes as a consequence.

  5. Cold exposure potentiates the effect of insulin on in vivo glucose uptake

    International Nuclear Information System (INIS)

    Vallerand, A.L.; Perusse, F.; Bukowiecki, L.J.

    1987-01-01

    The effects of cold exposure and insulin injection on the rates of net 2-[ 3 H]deoxyglucose uptake (K i ) in peripheral tissues were investigated in warm-acclimated rats. Cold exposure and insulin treatment independently increased K i values in skeletal muscles, heart, white adipose tissue, and brown adipose tissue. The effects of cold exposure were particularly evident in brown adipose tissue where the K i increased >100 times. When the two treatments were combined, it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an insulin-like effect on K i that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from (1) an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and (2) an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake

  6. Screening for bioactive metabolites in plant extracts modulating glucose uptake and fat accumulation

    DEFF Research Database (Denmark)

    El-Houri, Rime Bahij; Kotowska, Dorota Ewa; C. B. Olsen, Louise

    2014-01-01

    Dichloromethane and methanol extracts of seven different food and medicinal plants were tested in a screening platform for identification of extracts with potential bioactivity related to insulin-dependent glucose uptake and fat accumulation. The screening platform included a series of in vitro...

  7. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    Directory of Open Access Journals (Sweden)

    Nigel Beaton

    2015-11-01

    Conclusions: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

  8. Cold exposure potentiates the effect of insulin on in vivo glucose uptake

    Energy Technology Data Exchange (ETDEWEB)

    Vallerand, A.L.; Perusse, F.; Bukowiecki, L.J. (Laval Univ. School of Medicine, Quebec (Canada))

    1987-08-01

    The effects of cold exposure and insulin injection on the rates of net 2-({sup 3}H)deoxyglucose uptake (K{sub i}) in peripheral tissues were investigated in warm-acclimated rats. Cold exposure and insulin treatment independently increased K{sub i} values in skeletal muscles, heart, white adipose tissue, and brown adipose tissue. The effects of cold exposure were particularly evident in brown adipose tissue where the K{sub i} increased >100 times. When the two treatments were combined, it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an insulin-like effect on K{sub i} that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from (1) an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and (2) an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake.

  9. Exercise and Type 2 Diabetes: Molecular Mechanisms Regulating Glucose Uptake in Skeletal Muscle

    Science.gov (United States)

    Stanford, Kristin I.; Goodyear, Laurie J.

    2014-01-01

    Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial…

  10. Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation.

    Science.gov (United States)

    Osmond, D T; Nolan, C J; King, R G; Brennecke, S P; Gude, N M

    2000-05-01

    Gestational diabetes is associated with complications for the offspring before, during and after delivery. Poor maternal glucose control, however, is a weak predictor of these complications. Given its position at the interface of the maternal and fetal circulations, the placenta possibly plays a crucial part in protecting the fetus from adverse effects from the maternal diabetic milieu. We hypothesised that gestational diabetes may result in changes in placental function, particularly with respect to the uptake, transfer, and/or utilisation of glucose. We aimed to examine glucose transport and utilisation in intact human placental lobules from women with gestational diabetes and those from normal pregnancies. Dual perfusion of an isolated placental lobule was done on placentae from diet treated gestational diabetic (n = 7) and normal pregnant patients (n = 9) using maternal glucose concentrations of 4, 8, 16 and 24 mmol/l in random order over a 4-h experiment. Results were expressed in micromol x min(-1) x g(-1). D-glucose uptake from the maternal circulation (control 0.492 vs gestational diabetes mellitus 0.248, at 8 mmol/l maternal glucose), D-glucose utilisation by the placenta (0.255 vs 0.129), D-glucose transfer to the fetal circulation (direct 0.979 vs 0.402; net transfer 0.269 vs 0.118) and L-lactate maternal release into both the fetal (0.052 vs 0.042) and maternal (0.255 vs 0.129) circulation were significantly reduced during in vitro perfusion of placentae from patients with gestational diabetic pregnancies. Transfer of 3H-L-glucose also significantly reduced in the diabetic group (8.1% vs 2.6%). These results suggest that placental transport and metabolism of D-glucose is altered during gestational diabetes.

  11. Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2017-04-01

    Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

  12. Ciclazindol and mazindol on glucose uptake into human isolated skeletal muscle: no interaction of mazindol with methysergide.

    Science.gov (United States)

    Kirby, M J; Turner, P

    1977-01-01

    1 Ciclazindol, like mazindol, produced a significant concentration-dependent increase in glucose-uptake into human skeletal muscle in both the presence and absence of insulin. 2 Methysergide, which inhibits the action of fenfluramine on glucose-uptake into skeletal muscle, did not influence the effect of mazindol. PMID:901738

  13. A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes

    Directory of Open Access Journals (Sweden)

    Michael S. Scully

    2011-01-01

    Full Text Available Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of 14C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.

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

    International Nuclear Information System (INIS)

    Kuhl, D.E.; Metter, E.J.; Benson, D.F.; Ashford, J.W.; Riege, W.H.; Fujikawa, D.G.; Markham, C.H.; Maltese, A.

    1985-01-01

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

  15. In vivo cellular uptake of glutamate is impaired in the rat hippocampus during and after transient cerebral ischemia

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    2001-01-01

    . The present study is the first to investigate uptake of glutamate in the intact rat brain in relation to cerebral ischemia. Evidence is provided that uptake of Glu is restrained during ischemia, and that in the hours after ischemia, the extracellular turnover of glutamate is decreased. In the course...

  16. Ciliary Neurotrophic Factor Stimulates Muscle Glucose Uptake by a PI3-Kinase–Dependent Pathway That Is Impaired With Obesity

    Science.gov (United States)

    Steinberg, Gregory R.; Watt, Matthew J.; Ernst, Matthias; Birnbaum, Morris J.; Kemp, Bruce E.; Jørgensen, Sebastian Beck

    2009-01-01

    OBJECTIVE Ciliary neurotrophic factor (CNTF) reverses muscle insulin resistance by increasing fatty acid oxidation through gp130-LIF receptor signaling to the AMP-activated protein kinase (AMPK). CNTF also increases Akt signaling in neurons and adipocytes. Because both Akt and AMPK regulate glucose uptake, we investigated muscle glucose uptake in response to CNTF signaling in lean and obese mice. RESEARCH DESIGN AND METHODS Mice were injected intraperitoneally with saline or CNTF, and blood glucose was monitored. The effects of CNTF on skeletal muscle glucose uptake and AMPK/Akt signaling were investigated in incubated soleus and extensor digitorum longus (EDL) muscles from muscle-specific AMPKα2 kinase-dead, gp130ΔSTAT, and lean and obese ob/ob and high-fat–fed mice. The effect of C2-ceramide on glucose uptake and gp130 signaling was also examined. RESULTS CNTF reduced blood glucose and increased glucose uptake in isolated muscles in a time- and dose-dependent manner with maximal effects after 30 min with 100 ng/ml. CNTF increased Akt-S473 phosphorylation in soleus and EDL; however, AMPK-T172 phosphorylation was only increased in soleus. Incubation of muscles from AMPK kinase dead (KD) and wild-type littermates with the PI3-kinase inhibitor LY-294002 demonstrated that PI3-kinase, but not AMPK, was essential for CNTF-stimulated glucose uptake. CNTF-stimulated glucose uptake and Akt phosphorylation were substantially reduced in obesity (high-fat diet and ob/ob) despite normal induction of gp130/AMPK signaling—effects also observed when treating myotubes with C2-ceramide. CONCLUSIONS CNTF acutely increases muscle glucose uptake by a mechanism involving the PI3-kinase/Akt pathway that does not require AMPK. CNTF-stimulated glucose uptake is impaired in obesity-induced insulin resistance and by ceramide. PMID:19136654

  17. Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

    OpenAIRE

    Stuart, Charles A.; Ross, Ian R.; Howell, Mary E. A.; McCurry, Melanie P.; Wood, Thomas G.; Ceci, Jeffrey D.; Kennel, Stephen J.; Wall, Jonathan

    2011-01-01

    Mouse brain expresses three principle glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3−/− genotype is intrauterine lethal by seven days post-coitis, but the heterozygous (Glut3+/−) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberration...

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  19. Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes.

    Directory of Open Access Journals (Sweden)

    Yonghan He

    Full Text Available BACKGROUND: Ursolic acid (UA, a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels. OBJECTIVE: The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes. METHODS AND RESULTS: The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively. 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI 3-kinase (PI3K inhibitor wortmannin (1 µM, but not by SB203580 (10 µM, the inhibitor of mitogen-activated protein kinase (MAPK, or compound C (2.5 µM, the inhibitor of AMP-activated kinase (AMPK inhibitor. Furthermore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK and phosphoinositide-dependent serine/threoninekinase (AKT were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC and the expression of glucose transporter 4 (GLUT4 were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied. CONCLUSIONS: Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect.

  20. Cerebral glucose metabolic differences in patients with panic disorder

    International Nuclear Information System (INIS)

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M.

    1990-01-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task

  1. Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations

    DEFF Research Database (Denmark)

    Hespel, P; Richter, Erik

    1990-01-01

    on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C-3-O-methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen-depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular......1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet......, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats...

  2. Global reduction of cerebral glucose metabolism in persons with symptomatic as well as asymptomatic lacunar infarction

    International Nuclear Information System (INIS)

    Takahashi, Wakoh; Takagi, Shigeharu; Shinohara, Yukito; Ide, Michiru; Shohtsu, Akira

    2000-01-01

    To clarify the hemodynamic changes in lacunar infarction, we evaluated cerebral glucose metabolism by using positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) in patients with asymptomatic and symptomatic lacunar infarction and in persons without cerebral infarction on MRI. Subjects in this study were 27 patients with symptomatic lacunar infarction (SCI group), 73 subjects with asymptomatic lacunar infarction (ACI group), and 134 persons without infarction (NC group). CMRgI in the ACI group was significantly lower than that in the NC group in the cerebral cortex (P<0.05) and thalamus (P<0.05). CMRgI in the SCI group was significantly reduced from that in the NC group in the cerebral cortex (P<0.005), basal ganglia (P<0.001), thalamus (P<0.05) and white matter (P<0.005). The reduction in CMRgI in the SCI group was more severe than that in the ACI group in basal ganglia (P<0.05) and thalamus (P<0.05). Our results indicated that glucose metabolism in patients with asymptomatic lacunar infarction is reduced throughout the whole brain as compared with non-infarcted elderly persons. Follow-up and treatment of risk factors if present, may be necessary in such patients. (author)

  3. 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.

  4. ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism.

    Science.gov (United States)

    Chaudhari, Aditi; Håversen, Liliana; Mobini, Reza; Andersson, Linda; Ståhlman, Marcus; Lu, Emma; Rutberg, Mikael; Fogelstrand, Per; Ekroos, Kim; Mardinoglu, Adil; Levin, Malin; Perkins, Rosie; Borén, Jan

    2016-11-01

    Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids). Microarray analysis showed that ARAP2 knockdown altered expression of genes involved in sphingolipid metabolism. Because sphingolipids are known to play a key role in cell signaling, we performed lipidomics to further investigate the relationship between ARAP2 and sphingolipids and potentially identify a link with glucose uptake. We found that ARAP2 knockdown increased glucosylceramide and lactosylceramide levels without affecting ceramide levels, and thus speculated that the rate-limiting enzyme in glycosphingolipid synthesis, namely glucosylceramide synthase (GCS), could be modified by ARAP2. In agreement with our hypothesis, we showed that the activity of GCS was increased by ARAP2 knockdown and reduced by ARAP2 overexpression. Furthermore, pharmacological inhibition of GCS resulted in increases in basal glucose uptake, total GLUT1 levels, triglyceride biosynthesis from glucose, and lipid droplet formation, indicating that the effects of GCS inhibition are the opposite to those resulting from ARAP2 knockdown. Taken together, our data suggest that ARAP2 promotes lipid droplet formation by modifying sphingolipid metabolism through GCS. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Appropriate uptake period for myocardial PET imaging with 18F-FDG after oral glucose loading

    International Nuclear Information System (INIS)

    Brink, I.; Hentschell, M.; Hoegerle, S.; Moser, E.; Nitzsche, E.U.; Mix, M.; Schindler, T.

    2003-01-01

    Aim: Identification of a rationale for the appropriate uptake period for myocardial 18 F-FDG-PET imaging of patients with and without diabetes mellitus. Methods: In a subset of 27 patients, static 2D-PET examination was performed of patients with chronic coronary artery disease and known myocardial infarction. The patients fasted (at least 4 h) before examination. 18 F-FDG (330 ± 20 MBq) was injected intravenously. The image quality was semiquantitativly determined by ROI-analysis and the myocardium-to-blood pool activity ratio (M/B) was calculated. I.) Scans 30, 60, and 90 min p. i. of 10 non-diabetic patients (60 g oral glucose loading one hour before FDG-injection, low-dose intravenous insulin bolus if necessary). II.) Scans 30, 60, and 90 min p. i. of 10 patients with known non-insulin dependent diabetes (20 g glucose, insulin bolus). III.) Scans 90 min p. i. of 7 patients with known non-insulin dependent diabetes and elevated fasting serum glucose level (140-200 mg/dl; insulin bolus, no glucose). Results: I.) The M/B ratio significantly increases in non-diabetic patients with the uptake time (30 min 1.95 ± 0.20; 60 min 2.96 ± 0.36; 90 min 3.78 ± 0.43). II.) In patients with non-insulin dependent diabetes the M/B ratio also significantly increases with uptake time. Compared to non-diabetic patients group II reached smaller M/B values (30 min 1.56 ± 0.10; 60 min 2.15 ± 0.14; 90 min 2.71 ± 0.19). III.) In the group of patients with elevated fasting serum glucose level (who only got insulin but no glucose loading) the M/B activity ratio 90 min p. i. was clearly inferior compared with diabetic patients after oral glucose loading and insulin administration (M/B 2.71 ± 0.19 versus 2.16 ± 0.07). Conclusions: In static myocardial viability PET studies with 18 F-FDG an uptake time of 90 min yields image quality superior to that obtained after shorter uptake time. (orig.) [de

  6. Regional cerebral glucose metabolism in frontotemporal lobar degeneration

    International Nuclear Information System (INIS)

    Park, J.M.; Cho, S.S.; Lee, K.-H.; Choi, Y.; Choe, Y.S.; Kim, B.-T.; Kim, S.E.; Kwon, J.C.; Na, D.L.

    2002-01-01

    Purpose: Frontotemporal lobar degeneration (FTLD) is the third most common cause of dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neuro behavioral syndromes can be produced by FTLD: frontotemporal dementia (FTD), frontotemporal dementia with motor neuron disease (MND), semantic dementia (SD), and progressive aphasia (PA). We investigated patterns of metabolic impairment in patients with FTLD presented with four different clinical syndromes. Methods: We analyzed glucose metabolic patterns on FDG PET images obtained from 34 patients with a clinical diagnosis of FTLD (19 FTD, 6 MND, 6 SD, and 3 PA, according to a consensus criteria for clinical syndromes associated with FTLD) and 7 age-matched healthy controls using SPM99. Results: Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral pre-motor area was shown in patients with MND. Patients with SD had metabolic deficit in the left posterior temporal cortex including Wernicke's area, while hypometabolism in the bilateral inferior frontal gyrus including Broca's area and left angular gyrus was seen in patients with PA. These metabolic patterns were well correlated with clinical and neuropsychological features of FTLD syndromes. Conclusion: These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD

  7. Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients

    DEFF Research Database (Denmark)

    Nielsen, Roni; Jorsal, Anders; Iversen, Peter

    2017-01-01

    BACKGROUND: The glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF...... reserve (MFR). METHODS AND RESULTS: CHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design. Changes in MGU during an oral glucose tolerance test (OGTT...

  8. GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

    2014-01-01

    The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

  9. Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles.

    Science.gov (United States)

    Lin, Xuzhu; Parker, Lewan; Mclennan, Emma; Zhang, Xinmei; Hayes, Alan; McConell, Glenn; Brennan-Speranza, Tara C; Levinger, Itamar

    2017-01-01

    Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade. Extensor digitorum longus (EDL) and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204) and AS160 (Thr642) in both muscle types and increased mTOR phosphorylation (Ser2481) in EDL only. ucOC had no significant effect on the phosphorylation of AMPKα (Thr172). The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions.

  10. Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles

    Directory of Open Access Journals (Sweden)

    Xuzhu Lin

    2017-11-01

    Full Text Available Emerging evidence suggests that undercarboxylated osteocalcin (ucOC improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK, adenosine monophosphate-activated protein kinase (AMPK, and/or the mechanistic target of rapamycin complex 2 (mTORC2-protein kinase B (AKT-AKT substrate of 160 kDa (AS160 signaling cascade. Extensor digitorum longus (EDL and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204 and AS160 (Thr642 in both muscle types and increased mTOR phosphorylation (Ser2481 in EDL only. ucOC had no significant effect on the phosphorylation of AMPKα (Thr172. The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions.

  11. Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and production in human HepG2 cells.

    Science.gov (United States)

    Cordero-Herrera, Isabel; Martín, María Ángeles; Goya, Luis; Ramos, Sonia

    2014-02-01

    Insulin resistance is the primary characteristic of type 2 diabetes. Cocoa and its main flavanol, (-)-epicatechin (EC), display some antidiabetic effects, but the mechanisms for their preventive activities related to glucose metabolism and insulin signalling in the liver remain largely unknown. In the present work, the preventive effect of EC and a cocoa polyphenolic extract (CPE) on insulin signalling and on both glucose production and uptake are studied in insulin-responsive human HepG2 cells treated with high glucose. Pre-treatment of cells with EC or CPE reverted decreased tyrosine-phosphorylated and total levels of IR, IRS-1 and -2 triggered by high glucose. EC and CPE pre-treatment also prevented the inactivation of the PI3K/AKT pathway and AMPK, as well as the diminution of GLUT-2 levels induced by high glucose. Furthermore, pre-treatment of cells with EC and CPE avoided the increase in PEPCK levels and the diminished glucose uptake provoked by high glucose, returning enhanced levels of glucose production and decreased glycogen content to control values. These findings suggest that EC and CPE improved insulin sensitivity of HepG2 treated with high glucose, preventing or delaying a potential hepatic dysfunction through the attenuation of the insulin signalling blockade and the modulation of glucose uptake and production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Upregulation of glucose uptake in L8 myotubes by the extract from Lagerstroemia speciosa: a possible mechanism of action

    Directory of Open Access Journals (Sweden)

    Juntipa Purintrapiban

    2009-12-01

    Full Text Available The leaf of Lagerstroemia speciosa L. is used as an anti-diabetic herbal remedy in many countries. In an attempt to discover mechanisms of action of the L. speciosa extract that stimulate glucose uptake, a cell-based radioactive assay of glucose uptake was performed using L8 muscle cells. In this study, the methanol fraction of L. speciosa leaves (LSE contained a high level of phenolic compounds and showed strong capability to stimulate glucose uptake in a dose-dependent manner. The LSE stimulation was slightly inhibited (8.8% by SB203580. The inhibitory effect (23.6% of wortmannin on LSE-stimulated glucose uptake was demonstrated, suggesting LSE action on glucose transporter translocation. LSE-induced glucose uptake was completely reversed by cycloheximide. In addition, an increased amount of total glucose-transporter-1 protein was observed indicating that new protein synthesis is necessary for elevated glucose transport. LSE also enhanced insulin-stimulated glucose transport. These results suggest that LSE action may be mediated primarily via the synthesis of new transporters and involve both insulin-dependent and independent pathways.

  13. Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Veronica; Saraff, Kumuda [Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262 (United States); Medh, Jheem D., E-mail: jheem.medh@csun.edu [Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262 (United States)

    2009-11-06

    Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.

  14. Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

    International Nuclear Information System (INIS)

    Lopez, Veronica; Saraff, Kumuda; Medh, Jheem D.

    2009-01-01

    Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-γ) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-γ activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-γ in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.

  15. Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

    Science.gov (United States)

    Mleczko, Justyna; Ortega, Francisco J.; Falcon‐Perez, Juan Manuel; Wabitsch, Martin; Fernandez‐Real, Jose Manuel

    2018-01-01

    Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. PMID:29292863

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-05-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  19. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.

    OpenAIRE

    Castillo, C; Bogardus, C; Bergman, R; Thuillez, P; Lillioja, S

    1994-01-01

    Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of art...

  20. In vitro glucose uptake by isolated rat hemi-diaphragm study of Aegle marmelos Correa root

    Directory of Open Access Journals (Sweden)

    Subban Ravi

    2009-03-01

    Full Text Available The methanol extract of the root of Aegle marmelos, a medicinal plant, was fractionated into eight fractions using column chromatography. The anti-diabetic activity of all the fractions was studied using the glucose uptake by isolated rat hemi-diaphragm in vitro model. Using the bioassay-guided fractionation, two compounds 1 and 2 were isolated by column chromatography and identified as 6-methyl-4-chromanone and skimmianine respectively by NMR and mass spectral methods.

  1. Double-label autoradiographic deoxyglucose method for sequential measurement of regional cerebral glucose utilization

    Energy Technology Data Exchange (ETDEWEB)

    Redies, C.; Diksic, M.; Evans, A.C.; Gjedde, A.; Yamamoto, Y.L.

    1987-08-01

    A new double-label autoradiographic glucose analog method for the sequential measurement of altered regional cerebral metabolic rates for glucose in the same animal is presented. This method is based on the sequential injection of two boluses of glucose tracer labeled with two different isotopes (short-lived /sup 18/F and long-lived /sup 3/H, respectively). An operational equation is derived which allows the determination of glucose utilization for the time period before the injection of the second tracer; this equation corrects for accumulation and loss of the first tracer from the metabolic pool occurring after the injection of the second tracer. An error analysis of this operational equation is performed. The double-label deoxyglucose method is validated in the primary somatosensory (''barrel'') cortex of the anesthetized rat. Two different rows of whiskers were stimulated sequentially in each rat; the two periods of stimulation were each preceded by an injection of glucose tracer. After decapitation, dried brain slices were first exposed, in direct contact, to standard X-ray film and then to uncoated, ''tritium-sensitive'' film. Results show that the double-label deoxyglucose method proposed in this paper allows the quantification and complete separation of glucose utilization patterns elicited by two different stimulations sequentially applied in the same animal.

  2. Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography

    International Nuclear Information System (INIS)

    Yanai, Kazuhiko; Tohoku Univ., Sendai; Iinuma, Kazuie; Miyabayashi, Shigeaki; Narisawa, Kuniaki; Tada, Keiya; Matsuzawa, Taiju; Tohoku Univ., Sendai; Ito, Masatoshi; Yamada, Kenji

    1987-01-01

    We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P<0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two sibling with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE. (orig.)

  3. Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yanai, Kazuhiko; Iinuma, Kazuie; Miyabayashi, Shigeaki; Narisawa, Kuniaki; Tada, Keiya; Matsuzawa, Taiju; Ito, Masatoshi; Yamada, Kenji

    1987-09-01

    We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P<0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two sibling with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE.

  4. Effects of ketamine on glucose uptake by glucose transporter type 3 expressed in Xenopus oocytes: The role of protein kinase C

    Energy Technology Data Exchange (ETDEWEB)

    Tomioka, Shigemasa, E-mail: tomioka@dent.tokushima-u.ac.jp [Department of Dental Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan); Kaneko, Miyuki [Department of Dental Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan); Satomura, Kazuhito [First Department of Oral and Maxillofacial Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan); Mikyu, Tomiko; Nakajo, Nobuyoshi [Department of Dental Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan)

    2009-10-09

    We investigated the effects of ketamine on the type 3 facilitative glucose transporter (GLUT3), which plays a major role in glucose transport across the plasma membrane of neurons. Human-cloned GLUT3 was expressed in Xenopus oocytes by injection of GLUT3 mRNA. GLUT3-mediated glucose uptake was examined by measuring oocyte radioactivity following incubation with 2-deoxy-D-[1,2-{sup 3}H]glucose. While ketamine and S(+)-ketamine significantly increased GLUT3-mediated glucose uptake, this effect was biphasic such that higher concentrations of ketamine inhibited glucose uptake. Ketamine (10 {mu}M) significantly increased V{sub max} but not K{sub m} of GLUT3 for 2-deoxy-D-glucose. Although staurosporine (a protein kinase C inhibitor) increased glucose uptake, no additive or synergistic interactions were observed between staurosporine and racemic ketamine or S(+)-ketamine. Treatment with ketamine or S(+)-ketamine partially prevented GLUT3 inhibition by the protein kinase C activator phorbol-12-myrisate-13-acetate. Our results indicate that ketamine increases GLUT3 activity at clinically relevant doses through a mechanism involving PKC inhibition.

  5. Browning of white adipose tissue uncouples glucose uptake from insulin signaling.

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    Karin Mössenböck

    Full Text Available Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1 expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.

  6. Nuclear factor E2-related factor 2 knockdown enhances glucose uptake and alters glucose metabolism in AML12 hepatocytes.

    Science.gov (United States)

    Yuan, Xiaoyang; Huang, Huijing; Huang, Yi; Wang, Jinli; Yan, Jinhua; Ding, Ling; Zhang, Cuntai; Zhang, Le

    2017-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P glucose metabolism were then examined in AML12 cells under both high-glucose (33 mmol/L) and low-glucose (4.5 mmol/L) conditions. NK lowered the gene and protein expression of the anti-oxidases heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 and increased p-eukaryotic initiation factor-2α S51 , p-nuclear factor-κB p65 S276 , and its downstream proinflammatory factors, including interleukin-1 beta, tumor necrosis factor-α, matrix metalloproteinase 2, and matrix metalloproteinase 9, at the protein level. NK also altered the protein expression of fibroblast growth factor 21, glucose transporter type 4, insulin-like growth factor 1, forkhead box protein O1, p-AKT S473 , and p-GSK3α/β Y279/Y216 , which are involved in glucose uptake, glycogenesis, and gluconeogenesis in AML12 cells. Our results provide a comprehensive understanding of the central role of Nrf2 in the regulation of glucose metabolism in AML12 hepatocytes, in addition to its classical roles in the regulation of redox signaling, endoplasmic reticulum stress and proinflammatory responses, and support the potential of Nrf2 as a therapeutic target for the prevention and treatment of obesity and other associated metabolic syndromes. Impact statement Increasing evidence supports the complexity of Nrf2 functions beyond the antioxidant and detoxification response. Previous in vivo studies employing either Nrf2-knockout or Nrf2-activated mice have achieved a similar endpoint: protection against an obese and

  7. Portal Vein Glucose Entry Triggers a Coordinated Cellular Response That Potentiates Hepatic Glucose Uptake and Storage in Normal but Not High-Fat/High-Fructose–Fed Dogs

    OpenAIRE

    Coate, Katie C.; Kraft, Guillaume; Irimia, Jose M.; Smith, Marta S.; Farmer, Ben; Neal, Doss W.; Roach, Peter J.; Shiota, Masakazu; Cherrington, Alan D.

    2013-01-01

    The cellular events mediating the pleiotropic actions of portal vein glucose (PoG) delivery on hepatic glucose disposition have not been clearly defined. Likewise, the molecular defects associated with postprandial hyperglycemia and impaired hepatic glucose uptake (HGU) following consumption of a high-fat, high-fructose diet (HFFD) are unknown. Our goal was to identify hepatocellular changes elicited by hyperinsulinemia, hyperglycemia, and PoG signaling in normal chow-fed (CTR) and HFFD-fed d...

  8. Effect of exercise training on in vivo insulin-stimulated glucose uptake in intra-abdominal adipose tissue in rats

    DEFF Research Database (Denmark)

    Enevoldsen, L H; Stallknecht, B; Fluckey, J D

    2000-01-01

    ) and in subcutaneous AT and also studied the effect of training. Rats were either swim trained (15 wk, n = 9) or sedentary (n = 16). While the rats were under anesthesia, a hyperinsulinemic ( approximately 900 pM), euglycemic clamp was carried out and local glucose uptake was measured by both the 2-deoxy-D-[(3)H......]glucose and microdialysis techniques. Blood flow was measured by microspheres. Upon insulin stimulation, blood flow generally decreased in AT. Flow was higher in mesenteric tissue than in other ATs, whereas insulin-mediated glucose uptake did not differ between ATs. Training doubled the glucose infusion rate during...

  9. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

    Science.gov (United States)

    Kang, Changkeun; Lee, Hyunkyoung; Jung, Eun-Sun; Seyedian, Ramin; Jo, MiNa; Kim, Jehein; Kim, Jong-Shu; Kim, Euikyung

    2012-12-15

    Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, B; Larsen, J J; Mikines, K J

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration......-time: T, 44 +/- 9 min (n = 7); S, 102 +/- 23 min (n = 5); P training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis...

  11. Modulation of host central carbon metabolism and in situ glucose uptake by intracellular Trypanosoma cruzi amastigotes.

    Science.gov (United States)

    Shah-Simpson, Sheena; Lentini, Gaelle; Dumoulin, Peter C; Burleigh, Barbara A

    2017-11-01

    Obligate intracellular pathogens satisfy their nutrient requirements by coupling to host metabolic processes, often modulating these pathways to facilitate access to key metabolites. Such metabolic dependencies represent potential targets for pathogen control, but remain largely uncharacterized for the intracellular protozoan parasite and causative agent of Chagas disease, Trypanosoma cruzi. Perturbations in host central carbon and energy metabolism have been reported in mammalian T. cruzi infection, with no information regarding the impact of host metabolic changes on the intracellular amastigote life stage. Here, we performed cell-based studies to elucidate the interplay between infection with intracellular T. cruzi amastigotes and host cellular energy metabolism. T. cruzi infection of non-phagocytic cells was characterized by increased glucose uptake into infected cells and increased mitochondrial respiration and mitochondrial biogenesis. While intracellular amastigote growth was unaffected by decreased host respiratory capacity, restriction of extracellular glucose impaired amastigote proliferation and sensitized parasites to further growth inhibition by 2-deoxyglucose. These observations led us to consider whether intracellular T. cruzi amastigotes utilize glucose directly as a substrate to fuel metabolism. Consistent with this prediction, isolated T. cruzi amastigotes transport extracellular glucose with kinetics similar to trypomastigotes, with subsequent metabolism as demonstrated in 13C-glucose labeling and substrate utilization assays. Metabolic labeling of T. cruzi-infected cells further demonstrated the ability of intracellular parasites to access host hexose pools in situ. These findings are consistent with a model in which intracellular T. cruzi amastigotes capitalize on the host metabolic response to parasite infection, including the increase in glucose uptake, to fuel their own metabolism and replication in the host cytosol. Our findings enrich

  12. Cerebral uptake and retention of 99Tcsup(m)-hexamethylpropyleneamine oxime (99Tcsup(m)-HM-PAO)

    International Nuclear Information System (INIS)

    Holmes, R.A.; Chaplin, S.B.; Royston, K.G.; Missouri Univ., Columbia

    1985-01-01

    A new radiopharmaceutical, 99 Tcsup(m)-hexamethylpropyleneamine oxime ( 99 Tcsup(m)-HM-PAO) is described. This agent displays considerable promise for imaging cerebral blood flow. In studies in rats and one human volunteer, 99 Tcsup(m)-HM-PAO demonstrates good brain uptake, prolonged retention of activity in the brain, and slow regional redistribution. These properties suggest that this new radiopharmaceutical is ideal for single photon emission tomographic (SPECT) imaging of cerebral blood flow. (author)

  13. Relation of measured brain glucose utilisation and cerebral atrophy in man.

    Science.gov (United States)

    Schlageter, N L; Horwitz, B; Creasey, H; Carson, R; Duara, R; Berg, G W; Rapoport, S I

    1987-06-01

    The effect of cerebral atrophy on measured cerebral metabolic rates for glucose (CMRglc), as determined with positron emission tomography (PET), was examined in 49 healthy males aged 21-83 years. Global CMRglc and regional CMRglc for 34 grey matter regions parallel to and from 30 to 80 mm above the inferior orbital meatal (IOM) line were measured under resting conditions, using [18F]-fluorodeoxyglucose and an ECAT II positron emission tomograph. Using a GE 8800 CT/T scanner, slices parallel to and from 30 to 80 mm above the IOM line were analysed for CSF volume. Cerebral atrophy, indicated by increased CSF volume, was correlated significantly with global CMRglc, but accounted for no more than 13% of the variance in the CMRglc measurements. Methods for correcting for inter-subject variation in CSF volume were proposed. Global values for CMRglc, uncorrected or corrected for CSF volume, were found to be age invariant. These findings indicate that (a) cerebral atrophy has a small, but statistically significant effect on CMRglc as measured with PET; (b) CMRglc is age invariant in healthy males.

  14. Ecm33 is a novel factor involved in efficient glucose uptake for nutrition-responsive TORC1 signaling in yeast.

    Science.gov (United States)

    Umekawa, Midori; Ujihara, Masato; Nakai, Daiki; Takematsu, Hiromu; Wakayama, Mamoru

    2017-11-01

    Glucose uptake is crucial for providing both an energy source and a signal that regulates cell proliferation. Therefore, it is important to clarify the mechanisms underlying glucose uptake and its transmission to intracellular signaling pathways. In this study, we searched for a novel regulatory factor involved in glucose-induced signaling by using Saccharomyces cerevisiae as a eukaryotic model. Requirement of the extracellular protein Ecm33 in efficient glucose uptake and full activation of the nutrient-responsive TOR kinase complex 1 (TORC1) signaling pathway is shown. Cells lacking Ecm33 elicit a series of starvation-induced pathways even in the presence of extracellular high glucose concentration. This results in delayed cell proliferation, reduced ATP, induction of autophagy, and dephosphorylation of the TORC1 substrates Atg13 and Sch9. © 2017 Federation of European Biochemical Societies.

  15. Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease

    International Nuclear Information System (INIS)

    Kuwert, T.; Scholz, D.; Milz, M.; Herzog, H.; Feinendegen, L.E.; Hefter, H.; Weiss, P.; Arendt, G.; Loken, M.; Minnesota Univ., Minneapolis, MN; Hennerici, M.

    1992-01-01

    Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and - to a lesser extent - cortical and thalamic rCMRGlc were significantly decreased compared with controls. Striatal rCMRGlc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGlc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment. (orig.)

  16. Rac1 governs exercise‐stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice

    Science.gov (United States)

    Nielsen, Ida L.; Kleinert, Maximilian; Møller, Lisbeth L. V.; Ploug, Thorkil; Schjerling, Peter; Bilan, Philip J.; Klip, Amira; Jensen, Thomas E.; Richter, Erik A.

    2016-01-01

    Key point Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood.The GTPase Rac1 can be activated by muscle contraction and has been found to be necessary for insulin‐stimulated glucose uptake, although its role in exercise‐stimulated glucose uptake is unknown.We show that Rac1 regulates the translocation of the glucose transporter GLUT4 to the plasma membrane in skeletal muscle during exercise.We find that Rac1 knockout mice display significantly reduced glucose uptake in skeletal muscle during exercise. Abstract Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood. Despite extensive efforts, the signalling mechanisms vital for glucose uptake during exercise are not yet fully understood, although the GTPase Rac1 is a candidate molecule. The present study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise‐induced uptake of radiolabelled 2‐deoxyglucose at 65% of maximum running capacity was blocked in soleus muscle and decreased by 80% and 60% in gastrocnemius and tibialis anterior muscles, respectively, in muscle‐specific inducible Rac1 knockout (mKO) mice compared to wild‐type littermates. By developing an assay to quantify endogenous GLUT4 translocation, we observed that GLUT4 content at the sarcolemma in response to exercise was reduced in Rac1 mKO muscle. Our findings implicate Rac1 as a regulatory element critical for controlling glucose uptake during exercise via regulation of GLUT4 translocation. PMID:27061726

  17. Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

    Science.gov (United States)

    Heni, Martin; Wagner, Robert; Kullmann, Stephanie; Gancheva, Sofiya; Roden, Michael; Peter, Andreas; Stefan, Norbert; Preissl, Hubert; Häring, Hans-Ulrich; Fritsche, Andreas

    2017-07-01

    Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6- 2 H 2 ]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis. © 2017 by the American Diabetes Association.

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

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    BACKGROUND: The precise mechanism by which sevoflurane exerts its effects in the human brain remains unknown. In the present study, we quantified the effects of sevoflurane on regional cerebral glucose metabolism (rGMR) in the human brain measured with positron emission tomography. METHODS: Eight...... volunteers underwent two dynamic 18F-fluorodeoxyglucose positron emission tomography (PET) scans. One scan assessed conscious-baseline metabolism and the other scan assessed metabolism during 1 minimum alveolar concentration (MAC) sevoflurane anaesthesia. Cardiovascular and respiratory parameters were...... areas by 48-71% of the baseline (Pmetabolic reduction of GMR in all regions...

  20. Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake.

    Directory of Open Access Journals (Sweden)

    R Dhanya

    Full Text Available Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 μM showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-ylAmino-2-Deoxyglucose (2-NBDG on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control.

  1. Coupling of glutamate and glucose uptake in cultured Bergmann glial cells.

    Science.gov (United States)

    Mendez-Flores, Orquidia G; Hernández-Kelly, Luisa C; Suárez-Pozos, Edna; Najimi, Mustapha; Ortega, Arturo

    2016-09-01

    Glutamate, the main excitatory neurotransmitter in the vertebrate brain, exerts its actions through specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of sodium-dependent, glutamate uptake transporters mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing neuronal death. The sustained sodium influx associated to glutamate removal in glial cells, activates the sodium/potassium ATPase restoring the ionic balance, additionally, glutamate entrance activates glutamine synthetase, both events are energy demanding, therefore glia cells increase their ATP expenditure favouring glucose uptake, and triggering several signal transduction pathways linked to proper neuronal glutamate availability, via the glutamate/glutamine shuttle. To further characterize these complex transporters interactions, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity, plasma membrane localization and protein levels of glucose transporters was detected upon d-aspartate exposure. Interestingly, this increase is the result of a protein kinase C-dependent signaling cascade. Furthermore, a glutamate-dependent glucose and glutamate transporters co-immunoprecipitation was detected. These results favour the notion that glial cells are involved in glutamatergic neuronal physiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation

    DEFF Research Database (Denmark)

    Steensberg, Adam; van Hall, Gerrit; Keller, Charlotte

    2002-01-01

    -nor isotopic tracer-determined glucose uptake was higher in LCHO compared with HCHO in Series 2. However, arterial concentrations of insulin and glucose were lower, while free fatty acids and adrenaline were higher in LCHO compared with HCHO. These data suggest that pre-exercise glycogen content may influence...

  3. 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.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  5. Functional Analyse of GLUT1 and GLUT12 in Glucose Uptake in Goat Mammary Gland Epithelial Cells

    OpenAIRE

    Yu, Qinghua; Zhu, Liqi; Lin, Jian; Zhang, Qiang; Tian, Qi; Hu, Weiwei; Yang, Qian

    2013-01-01

    Glucose transport, mediated by glucose transporters, is necessary for mammary gland development and lactation. GLUT1 and GLUT12 could both be expressed in the pregnant and lactating mammary gland to participate in the glucose uptake process. In this study, the goat GLUT1 and GLUT12 genes were cloned from Saanen dairy goats and transfected into goat mammary gland epithelial cells to assess their biological functions and distributions. The results showed that both goat GLUT1 and GLUT12 had 12 p...

  6. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

    Directory of Open Access Journals (Sweden)

    Daphna D.J. Habets

    2012-09-01

    Full Text Available Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/ long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-λ knockout mice the roles of atypical PKCs (PKC-ζ and PKC-λ in regulating cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-λ ablation in cardiomyocytes. In contrast, myristoylated PKC-ζ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-λ-knockout cardiomyocytes. In PKC-λ knockout cardiomyocytes, PKC-ζ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-ζ activity in PKC-λ-knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-λ and PKC-ζ have interchangeable functions in these processes.

  7. Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPAR gamma and PI3K.

    Science.gov (United States)

    Kumar, Ramadhar; Balaji, S; Uma, T S; Sehgal, P K

    2009-12-10

    Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor. The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPAR gamma) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent. Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-D-[1-(3)H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPAR gamma and PI3K have been studied. The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 microg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPAR gamma and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake. This study demonstrated the significance of Glut-4, PPAR gamma and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.

  8. Sorption and Microbial Uptake of Alanine, Glucose and Acetate in Soil

    Science.gov (United States)

    Fischer, H.; Ingwersen, J.; Kuzyakov, Y.

    2009-04-01

    Low molecular weight organic substances (LMWOS), e. g. amino acids, sugars, and carboxylic acids, are C compounds that are most rapidly turned-over in the C cycle of soil. Despite of their importance it is still unknown how sorption to the soil matrix affects their turnover in soil solution. The goals of this study were (1) to describe the dynamics of the fluxes of LMWOS (10 µmol l-1) in various pools (dissolved, adsorbed, decomposed to CO2, incorporated into microbial biomass) and (2) to assess the LMWOS distribution in these pools in dependence of very wide range of concentration (0.01 to 1000 µmol l-1). Representatives of each LMWOS group (glucose for sugars, alanine for amino acids, Na-acetate for carboxylic acids) uniformly labeled with 14C were added to sterilized or non-sterilized soil and analyzed in dif-ferent compartments between 1 min and 5.6 hours after addition. LMWOS were almost completely taken up by microorganisms within the first 30 min. Microbial uptake was much faster than the physicochemical sorption (estimated in sterilized soil), which needed to reach quasi-equilibrium 60 min for alanine and about 400 min for glucose. Only sorption of acetate was instantaneous (>1 min). While for acetate the maximum sorption capacity was reached at 100 µmol l-1 no such maximum was found for glucose and alanine in the studied concentra-tion range. At the concentration of 100 µmol l-1, microbial decomposition after 4.5 h hours was higher for alanine (76.7±1.1%) than acetate (55.2±0.9%) and glucose (28.5±1.5%). On the contrary, incorporation into microbial biomass was higher for glucose (59.8±1.2%) than for acetate (23.4±5.9%) and alanine (5.2±2.8%). Within 10 to 500 µmol l-1 the pathways of the three LMWOS transformation changed: at 500 µmol l-1 alanine and acetate were less mineralized and more incorporated into microbial biomass than at 10 µmol l-1, while glucose incorporation decreased. Consequently, the concentrations of alanine, glucose, and

  9. Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation.

    Science.gov (United States)

    Goji, Takeo; Takahara, Kazuhiko; Negishi, Manabu; Katoh, Hironori

    2017-12-01

    Oncogenic signaling in cancer cells alters glucose uptake and utilization to supply sufficient energy and biosynthetic intermediates for survival and sustained proliferation. Oncogenic signaling also prevents oxidative stress and cell death caused by increased production of reactive oxygen species. However, elevated glucose metabolism in cancer cells, especially in glioblastoma, results in the cells becoming sensitive to glucose deprivation ( i.e. in high glucose dependence), which rapidly induces cell death. However, the precise mechanism of this type of cell death remains unknown. Here, we report that glucose deprivation alone does not trigger glioblastoma cell death. We found that, for cell death to occur in glucose-deprived glioblastoma cells, cystine and glutamine also need to be present in culture media. We observed that cystine uptake through the cystine/glutamate antiporter xCT under glucose deprivation rapidly induces NADPH depletion, reactive oxygen species accumulation, and cell death. We conclude that although cystine uptake is crucial for production of antioxidant glutathione in cancer cells its transport through xCT also induces oxidative stress and cell death in glucose-deprived glioblastoma cells. Combining inhibitors targeting cancer-specific glucose metabolism with cystine and glutamine treatment may offer a therapeutic approach for glioblastoma tumors exhibiting high xCT expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Inhibition of Saccharomyces cerevisiae growth by simultaneous uptake of glucose and maltose.

    Science.gov (United States)

    Hatanaka, Haruyo; Mitsunaga, Hitoshi; Fukusaki, Eiichiro

    2018-01-01

    Saccharomyces cerevisiae expresses α-glucoside transporters, such as MalX1p (X=1(Agt1p), 2, 3, 4, and 6), which are proton symporters. These transporters are regulated at transcriptional and posttranslational levels in the presence of glucose. Malt wort contains glucose, maltose, and maltotriose, and the assimilation of maltose is delayed as a function of glucose concentration. With the objective of increasing beer fermentation rates, we characterized α-glucoside transporters and bred laboratory yeasts that expressed various α-glucoside transporters for the simultaneous uptake of different sugars. Mal21p was found to be the most resistant transporter to glucose-induced degradation, and strain (HD17) expressing MAL21 grew on a medium containing glucose or maltose, but not on a medium containing both sugars (YPDM). This unexpected growth defect was observed on a medium containing glucose and >0.1% maltose but was not exhibited by a strain that constitutively expressed maltase. The defect depended on intracellular maltose concentration. Although maltose accumulation caused a surge in turgor pressure, addition of sorbitol to YPDM did not increase growth. When strain HD17 was cultivated in a medium containing only maltose, protein synthesis was inhibited at early times but subsequently resumed with reduction in accumulated maltose, but not if the medium was exchanged for YPDM. We conclude that protein synthesis was terminated under the accumulation of maltose, regardless of extracellular osmolarity, and HD17 could not resume growth, because the intracellular concentration of maltose did not decrease due to insufficient synthesis of maltase. Yeast should incorporate maltose after expressing adequate maltase in beer brewing. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  11. 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...... 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...... evaluable and regional cerebral metabolic rate for glucose (rCMRglc) was estimated in nontumoral brain regions in 12 patients treated with surgery alone and 9 patients treated with both surgery and CRT. Furthermore 10 normal controls matched for age at examination were included. Patients treated with both...

  12. In vivo cellular uptake of glutamate is impaired in the rat hippocampus during and after transient cerebral ischemia

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    2001-01-01

    Using microdialysis in CA1 of the rat hippocampus, we studied the effect of transient cerebral ischemia on in vivo uptake and on extracellular levels of glutamate during, and at different time points after ischemia. (3)H-D-aspartate (test substance), and (14)C-mannitol (reference substance), were...

  13. Inhibitory action of sphingosine, sphinganine and dexamethasone on glucose uptake: Studies with hydrogen peroxide and phorbol ester

    Energy Technology Data Exchange (ETDEWEB)

    Murray, D.K.; Hill, M.E.; Nelson, D.H. (Univ. of Utah School of Medicine, Salt Lake City (USA))

    1990-01-01

    The mechanism of the inhibitory action of glucocorticoids on glucose uptake is incompletely understood. Treatment with corticosteriods of cells in which glucose uptake is stimulated at insulin postbinding and postreceptor sites may clarify the site of the steroid inhibitory action. Hydrogen peroxide, which has been shown to stimulate the insulin receptor tyrosine kinase, and phorbol myristate acetate (PMA) which stimulates protein kinase C were, therefore, used as stimulators of glucose transport in this study. These studies demonstrate that dexamethasone and the sphingoid bases, sphinganine and sphingosine, inhibit glucose uptake that has been stimulated at either the receptor kinase or protein kinase C level in both 3T3-L1 and 3T3-C2 cells. These data confirm glucocorticoid inhibitory action at a post binding level and support the suggestion that some corticosteriod inhibitory effects may be mediated by an action on sphingolipid metabolism.

  14. Regional cerebral glucose metabolism after pridopidine (ACR16) treatment in patients with Huntington disease.

    Science.gov (United States)

    Esmaeilzadeh, Mouna; Kullingsjö, Johan; Ullman, Henrik; Varrone, Andrea; Tedroff, Joakim

    2011-01-01

    Huntington disease is a hereditary neurodegenerative disorder resulting in loss of motor, cognitive, and behavioral functions and is characterized by a distinctive pattern of cerebral metabolic abnormalities. Pridopidine (ACR16) belongs to a novel class of central nervous system compounds in development for the treatment of Huntington disease. The objective of the study was to investigate the metabolic changes in patients with Huntington disease before and after pridopidine treatment. [(18)F]Fluorodeoxyglucose positron emission tomographic imaging was used to measure the regional cerebral metabolic rate of glucose at baseline and after 14 days of open-label pridopidine treatment in 8 patients with Huntington disease. Clinical assessments were performed using the Unified Huntington's Disease Rating Scale. Statistical parametric mapping analysis showed increased metabolic activity in several brain regions such as the precuneus and the mediodorsal thalamic nucleus after treatment. In addition, after pridopidine treatment, the correlation between the clinical status and the cerebral metabolic activity was strengthened. Our findings suggest that pridopidine induces metabolic changes in brain regions implicated as important for mediating compensatory mechanisms in Huntington disease. In addition, the finding of a strong relationship between clinical severity and metabolic activity after treatment also suggests that pridopidine treatment targets a Huntington disease-related metabolic activity pattern.

  15. 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.)

  16. Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Liliana, E-mail: lilianam87@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Araújo, Isabel, E-mail: isa.araujo013@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Costa, Tito, E-mail: tito.fmup16@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Correia-Branco, Ana, E-mail: ana.clmc.branco@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Faria, Ana, E-mail: anafaria@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Chemistry Investigation Centre (CIQ), Faculty of Sciences of University of Porto, Rua Campo Alegre, 4169-007 Porto (Portugal); Faculty of Nutrition and Food Sciences of University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Martel, Fátima, E-mail: fmartel@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Keating, Elisa, E-mail: keating@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal)

    2013-07-15

    In this study we characterized {sup 3}H-2-deoxy-D-glucose ({sup 3}H -DG) uptake by the estrogen receptor (ER)-positive MCF7 and the ER-negative MDA-MB-231 human breast cancer cell lines and investigated the effect of quercetin (QUE) and epigallocatechin gallate (EGCG) upon {sup 3}H-DG uptake, glucose metabolism and cell viability and proliferation. In both MCF7 and MDA-MB-231 cells {sup 3}H-DG uptake was (a) time-dependent, (b) saturable with similar capacity (V{sub max}) and affinity (K{sub m}), (c) potently inhibited by cytochalasin B, an inhibitor of the facilitative glucose transporters (GLUT), (d) sodium-independent and (e) slightly insulin-stimulated. This suggests that {sup 3}H-DG uptake by both cell types is mediated by members of the GLUT family, including the insulin-responsive GLUT4 or GLUT12, while being independent of the sodium-dependent glucose transporter (SGLT1). QUE and EGCG markedly and concentration-dependently inhibited {sup 3}H-DG uptake by MCF7 and by MDA-MB-231 cells, and both compounds blocked lactate production by MCF7 cells. Additionally, a 4 h-treatment with QUE or EGCG decreased MCF7 cell viability and proliferation, an effect that was more potent when glucose was available in the extracellular medium. Our results implicate QUE and EGCG as metabolic antagonists in breast cancer cells, independently of estrogen signalling, and suggest that these flavonoids could serve as therapeutic agents/adjuvants even for ER-negative breast tumors. -- Highlights: • Glucose uptake by MCF7 and MDA-MB-231 cells is mainly mediated by GLUT1. • QUE and EGCG inhibit cellular glucose uptake thus abolishing the Warburg effect. • This process induces cytotoxicity and proliferation arrest in MCF7 cells. • The flavonoids’ effects are independent of estrogen receptor signalling.

  17. Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Walton, Felecia S.; Harmon, Anne W.; Paul, David S.; Drobna, Zuzana; Patel, Yashomati M.; Styblo, Miroslav

    2004-01-01

    Chronic exposures to inorganic arsenic (iAs) have been associated with increased incidence of noninsulin (type-2)-dependent diabetes mellitus. Although mechanisms by which iAs induces diabetes have not been identified, the clinical symptoms of the disease indicate that iAs or its metabolites interfere with insulin-stimulated signal transduction pathway or with critical steps in glucose metabolism. We have examined effects of iAs and methylated arsenicals that contain trivalent or pentavalent arsenic on glucose uptake by 3T3-L1 adipocytes. Treatment with inorganic and methylated pentavalent arsenicals (up to 1 mM) had little or no effect on either basal or insulin-stimulated glucose uptake. In contrast, trivalent arsenicals, arsenite (iAs III ), methylarsine oxide (MAs III O), and iododimethylarsine (DMAs III O) inhibited insulin-stimulated glucose uptake in a concentration-dependent manner. Subtoxic concentrations of iAs III (20 μM), MAs III O (1 μM), or DMAs III I (2 μM) decreased insulin-stimulated glucose uptake by 35-45%. Basal glucose uptake was significantly inhibited only by cytotoxic concentrations of iAs III or MAs III O. Examination of the components of the insulin-stimulated signal transduction pathway showed that all trivalent arsenicals suppressed expression and possibly phosphorylation of protein kinase B (PKB/Akt). The concentration of an insulin-responsive glucose transporter (GLUT4) was significantly lower in the membrane region of 3T3-L1 adipocytes treated with trivalent arsenicals as compared with untreated cells. These results suggest that trivalent arsenicals inhibit insulin-stimulated glucose uptake by interfering with the PKB/Akt-dependent mobilization of GLUT4 transporters in adipocytes. This mechanism may be, in part, responsible for the development of type-2 diabetes in individuals chronically exposed to iAs

  18. Correlation between TCA cycle flux and glucose uptake rate during respiro-fermentative growth of Saccharomyces cerevisiae.

    Science.gov (United States)

    Heyland, Jan; Fu, Jianan; Blank, Lars M

    2009-12-01

    Glucose repression of the tricarboxylic acid (TCA) cycle in Saccharomyces cerevisiae was investigated under different environmental conditions using (13)C-tracer experiments. Real-time quantification of the volatile metabolites ethanol and CO(2) allowed accurate carbon balancing. In all experiments with the wild-type, a strong correlation between the rates of growth and glucose uptake was observed, indicating a constant yield of biomass. In contrast, glycerol and acetate production rates were less dependent on the rate of glucose uptake, but were affected by environmental conditions. The glycerol production rate was highest during growth in high-osmolarity medium (2.9 mmol g(-1) h(-1)), while the highest acetate production rate of 2.1 mmol g(-1) h(-1) was observed in alkaline medium of pH 6.9. Under standard growth conditions (25 g glucose l(-1) , pH 5.0, 30 degrees C) S. cerevisiae had low fluxes through the pentose phosphate pathway and the TCA cycle. A significant increase in TCA cycle activity from 0.03 mmol g(-1) h(-1) to about 1.7 mmol g(-1) h(-1) was observed when S. cerevisiae grew more slowly as a result of environmental perturbations, including unfavourable pH values and sodium chloride stress. Compared to experiments with high glucose uptake rates, the ratio of CO(2) to ethanol increased more than 50 %, indicating an increase in flux through the TCA cycle. Although glycolysis and the ethanol production pathway still exhibited the highest fluxes, the net flux through the TCA cycle increased significantly with decreasing glucose uptake rates. Results from experiments with single gene deletion mutants partially impaired in glucose repression (hxk2, grr1) indicated that the rate of glucose uptake correlates with this increase in TCA cycle flux. These findings are discussed in the context of regulation of glucose repression.

  19. Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut

    International Nuclear Information System (INIS)

    Groot, Michel de; Meeuwis, Antoi P.W.; Kok, Peter J.M.; Corstens, Frans H.M.; Oyen, Wim J.G.

    2005-01-01

    Increased, non-pathological FDG uptake in myocardium, stomach and bowel is frequently observed while performing clinical positron emission tomography (PET) studies. This ''physiological'' increased FDG uptake is not related to (oncological) disease and is unwanted since it may interfere with correct image reading. We evaluated the role of several patient-related factors that may have an influence on this phenomenon. One hundred and seventy-five non-diabetic patients with malignant diseases, referred to our department for routine whole-body FDG-PET, were retrospectively evaluated. Age, blood glucose levels and duration of the fasting period were recorded. FDG uptake in myocardium, bowel and stomach was visually graded. Statistical analysis showed that increased FDG uptake in myocardium, bowel and stomach was not significantly correlated to blood glucose level, age or duration of fasting. Most patients who underwent repeated PET scans (92 scans in 25 patients), showed no or minor changes in uptake in bowel and stomach on the consecutive scans, while myocardial uptake was more variable. Age, fasting period and blood glucose levels did not influence physiological uptake. However, there seemed to be a patient-specific pattern for stomach and bowel uptake. (orig.)

  20. Evaluation of the relationship between physiological FDG uptake in the heart and age, blood glucose level, fasting period, and hospitalization

    International Nuclear Information System (INIS)

    Kaneta, Tomohiro; Hakamatsuka, Takashi; Takanami, Kentaro

    2006-01-01

    Positron emission tomography (PET) with fluorodeoxyglucose (FDG) is widely used for evaluation of cancer and ischemic heart disease. Recently, increased myocardial FDG uptake has been reported to be related to some types of heart disease, such as sarcoidosis. However, the physiological increased FDG uptake in the heart often mimics the abnormal high uptake in these cases. In this study, we investigated the relationships between myocardial uptake and age, blood glucose level, fasting period, and hospitalization status (inpatient vs. outpatient). A total of 159 non-diabetic patients were enrolled in the present study. Patients were imaged on a PET/CT scanner, and a three-dimensional region of interest (ROI) was drawn on the fused PET/CT image to measure the maximum standardized uptake value (SUV max ) of the whole left ventricle. No significant relationships were observed between myocardial uptake and age or fasting period. Blood glucose level showed a significant relationship (p=0.025) with myocardial uptake, but the R-square was extremely small (r 2 =0.03). With an SUV max threshold of 3.0, there was no significant difference between inpatients and outpatients. However, outpatients showed a significantly higher frequency of myocardial uptake over SUV max of 5.0 (x 2 test: p=0.046). It is difficult to predict the degree of physiological uptake in the heart from data regarding age, fasting period, or blood glucose level. Outpatients tend to show higher myocardial uptake than inpatients, which may make it difficult to detect abnormally increased uptake in the heart. A long fasting period, such as overnight fasting, is an inadequate means to reduce the physiological uptake of FDG in the heart. (author)

  1. Characterization of Secondary Metabolites from Purple Ipomoea batatas Leaves and Their Effects on Glucose Uptake.

    Science.gov (United States)

    Lee, Chia-Lin; Lee, Shou-Lun; Chen, Chao-Jung; Chen, Hsin-Chun; Kao, Ming-Ching; Liu, Chuan-Hao; Chen, Jau-Yang; Lai, Yen-Ting; Wu, Yang-Chang

    2016-06-08

    Ipomoea batatas has long been used in folk medicine for the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes. However, neither the plant extract nor its active components have been evaluated systematically. In this work four crude extracts, including n-hexane- (IBH), 95% MeOH- (IBM), n-BuOH- (IBB), and H₂O-soluble (IBW) fractions, were prepared by fractionation of a methanolic extract of purple I. batatas leaves. Twenty-four pure compounds 1-24 were then isolated by various chromatographic techniques and their structures identified from NMR and MS data. Glucose uptake assays in differentiated 3T3-L1 adipocytes and rat primary hepatocytes, as well as western blot analysis, were carried out to evaluate the antidiabetic activity of this species. The IBH crude fraction, with methyl decanoate (22) as a major and active compound, showed the greatest effect on glucose uptake, most likely via activation of Glut4 and regulation of the PI3K/AKT pathway. Quercetin 3-O-β-d-sophoroside (1), quercetin (3), benzyl β-d-glucoside (10), 4-hydroxy-3-methoxybenzaldehyde (12), and methyl decanoate (22) could be important components contributing to the antidiabetic effects. We conclude that purple I. batatas leaves have potential as an antidiabetic plant source and the active constituents 1, 3, 10, 12, and 22 are promising lead candidates for future investigation.

  2. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes.

    Science.gov (United States)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H; Skytt, Dorte M; Schousboe, Arne; Waagepetersen, Helle S

    2015-07-01

    Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100-500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels of extracellular glutamate independently of the GDH expression level. Moreover, increased intracellular glutamate content was observed in the GDH-deficient cells after a 2-hr incubation in the presence of 100 µM glutamate. It is significant that GDH-deficient cells exhibited an increased utilization of glucose in the presence of 250 and 500 µM glutamate, monitored as an increase in the accumulation of tritiated 2-deoxyglucose-6-phosphate. These findings underscore the importance of the expression level of GDH for the ability to utilize glutamate as an energy source fueling its own energy-requiring uptake. © 2015 Wiley Periodicals, Inc.

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

    International Nuclear Information System (INIS)

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

    1983-06-01

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

  4. Knockout of the predominant conventional PKC isoform, PKCalpha, in mouse skeletal muscle does not affect contraction-stimulated glucose uptake

    DEFF Research Database (Denmark)

    Jensen, Thomas E; Maarbjerg, Stine J; Rose, Adam J

    2009-01-01

    Conventional (c) protein kinase C (PKC) activity has been shown to increase with skeletal muscle contraction, and numerous studies using primarily pharmacological inhibitors have implicated cPKCs in contraction-stimulated glucose uptake. Here, to confirm that cPKC activity is required for contrac...... working on other parts of contraction-induced signaling or the remaining cPKC isoforms are sufficient for stimulating glucose uptake during contractions.......Conventional (c) protein kinase C (PKC) activity has been shown to increase with skeletal muscle contraction, and numerous studies using primarily pharmacological inhibitors have implicated cPKCs in contraction-stimulated glucose uptake. Here, to confirm that cPKC activity is required...... for contraction-stimulated glucose uptake in mouse muscles, contraction-stimulated glucose uptake ex vivo was first evaluated in the presence of three commonly used cPKC inhibitors (calphostin C, Gö-6976, and Gö-6983) in incubated mouse soleus and extensor digitorum longus (EDL) muscles. All potently inhibited...

  5. Heterogeneous effects of calorie restriction on in vivo glucose uptake and insulin signaling of individual rat skeletal muscles.

    Science.gov (United States)

    Sharma, Naveen; Sequea, Donel A; Castorena, Carlos M; Arias, Edward B; Qi, Nathan R; Cartee, Gregory D

    2014-01-01

    Calorie restriction (CR) (consuming ~60% of ad libitum, AL, intake) improves whole body insulin sensitivity and enhances insulin-stimulated glucose uptake by isolated skeletal muscles. However, little is known about CR-effects on in vivo glucose uptake and insulin signaling in muscle. Accordingly, 9-month-old male AL and CR (initiated when 3-months-old) Fischer 344 x Brown Norway rats were studied using a euglycemic-hyperinsulinemic clamp with plasma insulin elevated to a similar level (~140 µU/ml) in each diet group. Glucose uptake (assessed by infusion of [(14)C]-2-deoxyglucose, 2-DG), phosphorylation of key insulin signaling proteins (insulin receptor, Akt and Akt substrate of 160 kDa, AS160), abundance of GLUT4 and hexokinase proteins, and muscle fiber type composition (myosin heavy chain, MHC, isoform percentages) were determined in four predominantly fast-twitch (epitrochlearis, gastrocnemius, tibialis anterior, plantaris) and two predominantly slow-twitch (soleus, adductor longus) muscles. CR did not result in greater GLUT4 or hexokinase abundance in any of the muscles, and there were no significant diet-related effects on percentages of MHC isoforms. Glucose infusion was greater for CR versus AL rats (Pmuscles (epitrochlearis, gastrocnemius, tibialis anterior), without a significant diet-effect on 2-DG uptake by the plantaris or either slow-twitch muscle. Each of the muscles with a CR-related increase in 2-DG uptake was also characterized by significant (Pmuscles without a CR-related increase in glucose uptake, only the soleus had significant (Pmuscles. The results also demonstrated that CR does not uniformly enhance either insulin signaling or insulin-stimulated glucose uptake in all muscles in vivo.

  6. Heterogeneous Effects of Calorie Restriction on In Vivo Glucose Uptake and Insulin Signaling of Individual Rat Skeletal Muscles

    Science.gov (United States)

    Sharma, Naveen; Sequea, Donel A.; Castorena, Carlos M.; Arias, Edward B.; Qi, Nathan R.; Cartee, Gregory D.

    2013-01-01

    Calorie restriction (CR) (consuming ∼60% of ad libitum, AL, intake) improves whole body insulin sensitivity and enhances insulin-stimulated glucose uptake by isolated skeletal muscles. However, little is known about CR-effects on in vivo glucose uptake and insulin signaling in muscle. Accordingly, 9-month-old male AL and CR (initiated when 3-months-old) Fischer 344xBrown Norway rats were studied using a euglycemic-hyperinsulinemic clamp with plasma insulin elevated to a similar level (∼140 µU/ml) in each diet group. Glucose uptake (assessed by infusion of [14C]-2-deoxyglucose, 2-DG), phosphorylation of key insulin signaling proteins (insulin receptor, Akt and Akt substrate of 160kDa, AS160), abundance of GLUT4 and hexokinase proteins, and muscle fiber type composition (myosin heavy chain, MHC, isoform percentages) were determined in four predominantly fast-twitch (epitrochlearis, gastrocnemius, tibialis anterior, plantaris) and two predominantly slow-twitch (soleus, adductor longus) muscles. CR did not result in greater GLUT4 or hexokinase abundance in any of the muscles, and there were no significant diet-related effects on percentages of MHC isoforms. Glucose infusion was greater for CR versus AL rats (Pmuscles (epitrochlearis, gastrocnemius, tibialis anterior), without a significant diet-effect on 2-DG uptake by the plantaris or either slow-twitch muscle. Each of the muscles with a CR-related increase in 2-DG uptake was also characterized by significant (Pmuscles without a CR-related increase in glucose uptake, only the soleus had significant (Pmuscles. The results also demonstrated that CR does not uniformly enhance either insulin signaling or insulin-stimulated glucose uptake in all muscles in vivo. PMID:23755179

  7. Glucose Uptake Is Decreased in Affected Lower Leg Muscles of Hemiparetic Persons during Level Walking.

    Science.gov (United States)

    Oi, Naoyuki; Itoh, Masatoshi; Tobimatsu, Yoshiko; Konno, Shinichi; Kikuchi, Shinichi; Iwaya, Tsutomu

    2015-12-01

    Stroke patients suffer from gait disturbance due to altered leg muscle actions. Many kinesiological studies have investigated muscle actions, but the metabolic activity of muscles in stroke patients remains to be investigated. We therefore evaluated energy consumption in lower extremity muscles during level walking in hemiparetic individuals. Glucose uptake was measured by positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) in eight hemiparetic (mean age: 56 years) and 11 healthy (mean age: 26 years) participants. Standardized uptake ratio (SUR) was computed in each muscle to express the (18)F-FDG-uptake level. SUR was compared across gluteal, thigh, and lower leg muscles and across individual muscles within each muscle group. For each muscle, SUR was compared among the paretic limb of hemiparetic participants, the non-paretic limb of hemiparetic participants, and the right limb of healthy participants. In paretic limbs, mean SUR did not differ between the three muscle groups, or between individual muscles within each muscle group. SURs of paretic lower leg muscles and gluteus minimus muscle were significantly smaller than those of non-paretic limb and healthy participants (p limb of hemiparetic participants, SUR of the lower leg muscles was larger than that of the thigh muscles (p muscles were larger in the non-paretic limb of hemiparetic participants, compared to the right limb of healthy participants (p lower extremity muscles during level walking in hemiparetic individuals.

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

    International Nuclear Information System (INIS)

    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; Lim, Sang Moo

    2005-01-01

    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

  9. 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.

  10. Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity.

    Science.gov (United States)

    Virgin, C E; Ha, T P; Packan, D R; Tombaugh, G C; Yang, S H; Horner, H C; Sapolsky, R M

    1991-10-01

    Glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, can damage the hippocampus and impair its capacity to survive coincident neurological insults. This GC endangerment of the hippocampus is energetic in nature, as it can be prevented when neurons are supplemented with additional energy substrates. This energetic endangerment might arise from the ability of GCs to inhibit glucose transport into both hippocampal neurons and astrocytes. The present study explores the GC inhibition in astrocytes. (1) GCs inhibited glucose transport approximately 15-30% in both primary and secondary hippocampal astrocyte cultures. (2) The parameters of inhibition agreed with the mechanisms of GC inhibition of glucose transport in peripheral tissues: A minimum of 4 h of GC exposure were required, and the effect was steroid specific (i.e., it was not triggered by estrogen, progesterone, or testosterone) and tissue specific (i.e., it was not triggered by GCs in cerebellar or cortical cultures). (3) Similar GC treatment caused a decrease in astrocyte survival during hypoglycemia and a decrease in the affinity of glutamate uptake. This latter observation suggests that GCs might impair the ability of astrocytes to aid neurons during times of neurologic crisis (i.e., by impairing their ability to remove damaging glutamate from the synapse).

  11. Heterogeneous effects of calorie restriction on in vivo glucose uptake and insulin signaling of individual rat skeletal muscles.

    Directory of Open Access Journals (Sweden)

    Naveen Sharma

    Full Text Available Calorie restriction (CR (consuming ~60% of ad libitum, AL, intake improves whole body insulin sensitivity and enhances insulin-stimulated glucose uptake by isolated skeletal muscles. However, little is known about CR-effects on in vivo glucose uptake and insulin signaling in muscle. Accordingly, 9-month-old male AL and CR (initiated when 3-months-old Fischer 344 x Brown Norway rats were studied using a euglycemic-hyperinsulinemic clamp with plasma insulin elevated to a similar level (~140 µU/ml in each diet group. Glucose uptake (assessed by infusion of [(14C]-2-deoxyglucose, 2-DG, phosphorylation of key insulin signaling proteins (insulin receptor, Akt and Akt substrate of 160 kDa, AS160, abundance of GLUT4 and hexokinase proteins, and muscle fiber type composition (myosin heavy chain, MHC, isoform percentages were determined in four predominantly fast-twitch (epitrochlearis, gastrocnemius, tibialis anterior, plantaris and two predominantly slow-twitch (soleus, adductor longus muscles. CR did not result in greater GLUT4 or hexokinase abundance in any of the muscles, and there were no significant diet-related effects on percentages of MHC isoforms. Glucose infusion was greater for CR versus AL rats (P<0.05 concomitant with significantly (P<0.05 elevated 2-DG uptake in 3 of the 4 fast-twitch muscles (epitrochlearis, gastrocnemius, tibialis anterior, without a significant diet-effect on 2-DG uptake by the plantaris or either slow-twitch muscle. Each of the muscles with a CR-related increase in 2-DG uptake was also characterized by significant (P<0.05 increases in phosphorylation of both Akt and AS160. Among the 3 muscles without a CR-related increase in glucose uptake, only the soleus had significant (P<0.05 CR-related increases in Akt and AS160 phosphorylation. The current data revealed that CR leads to greater whole body glucose disposal in part attributable to elevated in vivo insulin-stimulated glucose uptake by fast-twitch muscles. The

  12. Regional cerebral glucose metabolism associated with ataxic gait. An FDG-PET activation study in patients with olivo-pontocerebellar atrophy

    International Nuclear Information System (INIS)

    Mishina, Masahiro; Ohyama, Masashi; Kitamura, Shin; Terashi, Akirou; Senda, Michio; Ishii, Kenji.

    1995-01-01

    In 7 patients with olivo-pontocerebellar atrophy (OPCA), regional cerebral glucose metabolism was evaluated using 18 F-FDG PET under two different conditions; 30 minutes' treadmill walking, and supine resting. The two sets of PET images were three-dimensionally registered to the MRI. Then, the PET images were normalized by the global value. Regions of interest (ROIs) were drawn on the cerebellar vermis, cerebellar hemispheres, pons, and thalamus, and FDG uptake was obtained to calculate the activation ratio (=[FDG uptake under walking]/ [FDG uptake under resting]) for each region. Normalized resting FDG uptake had no significant difference between controls and OPCA patients in any region. Activation ratio of OPCA patients was significantly decreased in the cerebellar vermis compared with the controls. In the controls, FDG uptake had little difference between resting and walking in the cerebellar hemisphere, pons and thalamus. On the other hand, the FDG uptake of OPCA patients was moderately increased by walking in these regions. The reduction of activation ratio in the cerebellar vermis reflects the dysfunction caused by degeneration. The result suggests that the PET activation study can demonstrate cerebellar dysfunction in the early phase of OPCA, in which other neuro-imaging methods cannot detect the tissue atrophy, hypometabolism or hypoperfusion in the resting state. In the cerebellar hemisphere, pons and thalamus, the activation ratio was nearly equal to one in control subjects, while it was larger in OPCA patients. The instability during the ataxic gait increases the inputs from the vestibular, somatosensory and visual systems to these regions and outputs from these regions to the other neural systems. In conclusion, PET activation study is a useful and noninvasive technique for investigating the brain function associated with human gait. (H.O.)

  13. Effects of MK-801 upon local cerebral glucose utilization in conscious rats and in rats anaesthetised with halothane

    International Nuclear Information System (INIS)

    Kurumaji, A.; McCulloch, J.

    1989-01-01

    The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilization were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilization with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus

  14. Rac1 governs exercise-stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice

    DEFF Research Database (Denmark)

    Sylow, Lykke; Laurent, Ida; Kleinert, Maximilian

    2016-01-01

    Exercise increase skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood. Despite extensive efforts, the signaling mechanisms vital for glucose uptake during exercise are not yet fully understood but the GTPase Rac1...... is a candidate molecule. This study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise-induced uptake of radiolabelled 2-deoxyglucose (2-DG) at 65% max running capacity was blocked in soleus and decreased by 80 and 60......% in gastrocnemius and tibialis anterior muscles, respectively, in muscle-specific inducible Rac1 knockout (mKO) mice compared to wildtype littermates. By developing an assay to quantify endogenous GLUT4 translocation, we observed that GLUT4 content at the sarcolemma in response to exercise was reduced in Rac1 m...

  15. Lycium barbarum L. Polysaccharide (LBP Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell

    Directory of Open Access Journals (Sweden)

    Huizhen Cai

    2017-02-01

    Full Text Available Lycium barbarum L. polysaccharide (LBP is prepared from Lycium barbarum L. (L. barbarum, which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1.

  16. Congenital vascular malformations - cerebral lesions differ from extracranial lesions by their immune expression of the glucose transporter protein GLUT1

    NARCIS (Netherlands)

    Meijer-Jorna, Lorine B.; Aronica, Eleonora; van der Loos, Chris M.; Troost, Dirk; van der Wal, Allard C.

    2012-01-01

    Background: Cerebral vascular malformations were investigated for the presence of the glucose transporter protein GLUT I, which is normally expressed in endothelial cells of the pre-existing microvasculature of the brain and absent in the vasculature of the choroid plexus and extracranial

  17. 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 art...

  18. Effects of high amphetamine dose on mood and cerebral glucose metabolism in normal volunteers using positron emission tomography (PET)

    NARCIS (Netherlands)

    Vollenweider, FX; Maguire, RP; Leenders, KL; Mathys, K; Angst, J

    1998-01-01

    The effects of high euphorigenic doses of D-amphetamine (0.9-1.0 mg/kg p.o.) on regional cerebral glucose metabolism (rCMRglu) and psychological measures were investigated in 10 healthy human volunteers using a within-subject design and [F-18]-fluorodeoxygrucose positron emission tomography

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-01-01

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

  20. Bilingualism as a contributor to cognitive reserve?Evidence from cerebral glucose metabolism in mild cognitive impairment and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Magdalena Eva Kowoll

    2016-04-01

    Full Text Available Objective: Bilingualism is discussed as one factor contributing to ‘cognitive reserve’ (CR as it enhances executive control functions. To elucidate the underlying cerebral correlates regional glucose uptake was compared between bilinguals and monolinguals with mild cognitive impairment (MCI and beginning Alzheimer´s disease (AD by using [18F]fluorodeoxyglucose (FDG positron emission tomography (PET. Methods: 30 patients (73.2 ± 7.4 diagnosed with MCI or probable AD received physical and neuropsychological examinations, blood tests and FDG-PET scans. 16 patients were classified as lifelong bilinguals following the criterion of Bialystok et al.; groups were matched for age, sex and MMSE scores. Analyses were conducted using SPM 8 using the whole brain as reference region for intensity normalization controlling for years of education.Results: Bilingual patient groups showed substantially greater impairment of glucose uptake in frontotemporal and parietal regions (including Brodmann areas 9, 47, 40 and 21 and in the left cerebellum relative to monolingual patients.Conclusions: Bilingualism is likely to contribute to CR given that bilingual patients showed more severe brain changes than monolinguals when adjusting for severity of cognitive impairment . The latter did not only comprise Brodmann areas relevant to speech and language but also structures typically involved in AD pathology such as the temporal and the parietal cortices.

  1. Effect of superfused insulin on cerebral cortical glucose utilization in awake goats

    International Nuclear Information System (INIS)

    Pelligrino, D.A.; Miletich, D.J.; Albrecht, R.F.

    1987-01-01

    The effect on cortical cerebral glucose utilization (CMR glu ) of intracerebral insulin administration in awake goats was studied. The insulin was superfused in a mock cerebrospinal fluid (CSF) employing chronically implanted cranial windows. Two windows were implanted bilaterally: one window over an equivalent portion of each parietal cortex. With one window used to deliver insulin/CSF and the other used to simultaneously deliver CSF alone (control), changes in CMR glu were assessed using a modification of a sequential 2-[ 3 H]- then 2[ 14 C]deoxy-D-glucose (2DG) technique originally described by Altenau and Agranoff. Initial experiments employing 125 I-insulin demonstrated that the superfusion procedure increased insulin levels only in the outer 1 mm of cortical tissue exposed to insulin containing perfusate. Additional preliminary evaluations, using conditions known to alter CMR glu , generally established that present methods were adequate to induce and detect CMR glu changes. However, it was also shown experimentally and using a mathematical model that 2-[ 3 H]DG test/control tissue ratios could be influenced by subsequent changes in CMR glu and the dephosphorylation rate. Thus 3 H ratios could not be used to establish preexperimental test/control CMR glu relationships as the originally devised model assumed but could be employed to indicate changes in dephosphorylation. The mathematical model allowed for improved estimates of CMR glu changes from 2[ 14 C]DG/2-[ 3 H]DG test over control tissue ratios. Even with these corrections, insulin was estimated to cause no more than an 8-15% increase in cortical CMR glu . A very limited role for insulin, at least in cerebral cortical metabolic regulation, is thus indicated

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

    International Nuclear Information System (INIS)

    Tyler, J.L.; Strother, S.C.; Zatorre, R.J.; Alivisatos, B.; Worsley, K.J.; Diksic, M.; Yamamoto, Y.L.

    1988-01-01

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

  3. Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK-mediated glucose uptake and adipogenesis pathways.

    Directory of Open Access Journals (Sweden)

    Nami Kim

    Full Text Available Dibenzoylmethane (DBM has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor. DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK, which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4 was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC, the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS, was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

  4. Cerebral blood flow and glucose metabolism measured with positron emission tomography are decreased in human type 1 diabetes.

    Science.gov (United States)

    van Golen, Larissa W; Huisman, Marc C; Ijzerman, Richard G; Hoetjes, Nikie J; Schwarte, Lothar A; Lammertsma, Adriaan A; Diamant, Michaela

    2013-08-01

    Subclinical systemic microvascular dysfunction exists in asymptomatic patients with type 1 diabetes. We hypothesized that microangiopathy, resulting from long-standing systemic hyperglycemia and hyperinsulinemia, may be generalized to the brain, resulting in changes in cerebral blood flow (CBF) and metabolism in these patients. We performed dynamic [(15)O]H2O and [(18)F]-fluoro-2-deoxy-d-glucose brain positron emission tomography scans to measure CBF and cerebral glucose metabolism (CMRglu), respectively, in 30 type 1 diabetic patients and 12 age-matched healthy controls after an overnight fast. Regions of interest were automatically delineated on coregistered magnetic resonance images and full kinetic analysis was performed. Plasma glucose and insulin levels were higher in patients versus controls. Total gray matter CBF was 9%, whereas CMRglu was 21% lower in type 1 diabetic subjects versus control subjects. We conclude that at real-life fasting glucose and insulin levels, type 1 diabetes is associated with decreased resting cerebral glucose metabolism, which is only partially explained by the decreased CBF. These findings suggest that mechanisms other than generalized microangiopathy account for the altered CMRglu observed in well-controlled type 1 diabetes.

  5. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H

    2015-01-01

    Cultured astrocytes treated with siRNA to knock down glutamate dehydrogenase (GDH) were used to investigate whether this enzyme is important for the utilization of glutamate as an energy substrate. By incubation of these cells in media containing different concentrations of glutamate (range 100......-500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP...... regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels...

  6. Uptake of glutamate is impaired in the cortical penumbra of the rat following middle cerebral artery occlusion

    DEFF Research Database (Denmark)

    Bruhn, Torben; Christensen, Thomas; Diemer, Nils Henrik

    2003-01-01

    was reduced transiently during periinfarct depolarizations. A mean of all extraction values obtained during MCAO in the penumbra group was reduced by 47% compared with a mean of values obtained before institution of MCAO. Induction of death resulted in a reduction of (3)H-D-aspartate extraction by 86......%. The present results provide direct evidence that uptake of Glu is reduced both in the ischemic core and in the penumbra of the cerebral cortex following MCAO in rats, possibly contributing to the initiation and spread of infarction. The results further indicate that uptake of Glu in the penumbra recovers...

  7. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of 18F-Fluorodeoxyglucose After Radiation Treatment

    International Nuclear Information System (INIS)

    Wilson, George D.; Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L.; Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John; Oliver Wong, Ching Yee; Yan, Di; Marples, Brian; Huang, Jiayi

    2014-01-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm 3 they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: 18 F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism

  8. Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

    Science.gov (United States)

    Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

    1987-01-01

    The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years and in 20 healthy men aged 45-64 years. All subjects were at rest with eyes covered and ears plugged. Mean hemispheric CMRglc in the older Down's syndrome subjects was significantly less, by 23%, than in the young Down's syndrome group; statistically significant decreases in regional metabolism (rCMRglc) also were present in all lobar regions. Comparison of the younger control group with the older control group showed no difference in CMRglc or any rCMRglc (p greater than 0.05). Assessment of language, visuospatial ability, attention and memory showed significant reductions in test scores of the old as compared with the young Down's syndrome subjects. These results show that significant age differences in CMRglc and rCMRglc occur in Down's syndrome but not in healthy controls, and that, although only some older Down's syndrome subjects are demented, significant age reductions in neuropsychologic variables occur in all of them. PMID:2956363

  9. Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

    Science.gov (United States)

    Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

    1987-06-01

    The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years and in 20 healthy men aged 45-64 years. All subjects were at rest with eyes covered and ears plugged. Mean hemispheric CMRglc in the older Down's syndrome subjects was significantly less, by 23%, than in the young Down's syndrome group; statistically significant decreases in regional metabolism (rCMRglc) also were present in all lobar regions. Comparison of the younger control group with the older control group showed no difference in CMRglc or any rCMRglc (p greater than 0.05). Assessment of language, visuospatial ability, attention and memory showed significant reductions in test scores of the old as compared with the young Down's syndrome subjects. These results show that significant age differences in CMRglc and rCMRglc occur in Down's syndrome but not in healthy controls, and that, although only some older Down's syndrome subjects are demented, significant age reductions in neuropsychologic variables occur in all of them.

  10. Rac1 and AMPK account for the majority of muscle glucose uptake stimulated by ex vivo contraction but not in vivo exercise

    DEFF Research Database (Denmark)

    Sylow, Lykke; Møller, Lisbeth Liliendal Valbjørn; Kleinert, Maximilian

    2017-01-01

    Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake...... deletion of Rac1.Muscle-specific knockout (mKO) of Rac1, a kinase dead α2 AMPK (α2KD), and double KO of β1 and β2 AMPK subunits (β1β2 KO), each partially decreased contraction-stimulated glucose transport in mouse soleus and EDL muscle. Interestingly, when pharmacological Rac1 inhibition was combined...... with either AMPK β1β2 KO or α2KD, contraction-stimulated glucose transport was almost completely inhibited. Importantly, α2KD+Rac1 mKO double-transgenic mice also displayed severely impaired contraction-stimulated glucose transport, while exercise-stimulated glucose uptake in vivo was only partially reduced...

  11. Regulation of myosin light chain kinase during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

    Directory of Open Access Journals (Sweden)

    Shelly Woody

    Full Text Available Myosin II (MyoII is required for insulin-responsive glucose transporter 4 (GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Our previous studies have shown that insulin signaling stimulates phosphorylation of the regulatory light chain (RLC of MyoIIA via myosin light chain kinase (MLCK. The experiments described here delineate upstream regulators of MLCK during insulin-stimulated glucose uptake. Since 3T3-L1 adipocytes express two MyoII isoforms, we wanted to determine which isoform was required for insulin-stimulated glucose uptake. Using a siRNA approach, we demonstrate that a 60% decrease in MyoIIA protein expression resulted in a 40% inhibition of insulin-stimulated glucose uptake. We also show that insulin signaling stimulates the phosphorylation of MLCK. We further show that MLCK can be activated by calcium as well as signaling pathways. We demonstrate that adipocytes treated with the calcium chelating agent, 1,2-b (iso-aminophenoxy ethane-N,N,N',N'-tetra acetic acid, (BAPTA (in the presence of insulin impaired the insulin-induced phosphorylation of MLCK by 52% and the RLC of MyoIIA by 45% as well as impairing the recruitment of MyoIIA to the plasma membrane when compared to cells treated with insulin alone. We further show that the calcium ionophore, A23187 alone stimulated the phosphorylation of MLCK and the RLC associated with MyoIIA to the same extent as insulin. To identify signaling pathways that might regulate MLCK, we examined ERK and CaMKII. Inhibition of ERK2 impaired phosphorylation of MLCK and insulin-stimulated glucose uptake. In contrast, while inhibition of CaMKII did inhibit phosphorylation of the RLC associated with MyoIIA, inhibition of CAMKIIδ did not impair MLCK phosphorylation or translocation to the plasma membrane or glucose uptake. Collectively, our results are the first to delineate a role for calcium and ERK in the activation of MLCK and thus MyoIIA during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

  12. Predicting Insulin Absorption and Glucose Uptake during Exercise in Type 1 Diabetes

    Science.gov (United States)

    Frank, Spencer; Hinshaw, Ling; Basu, Rita; Szeri, Andrew; Basu, Ananda

    2017-11-01

    A dose of insulin infused into subcutaneous tissue has been shown to absorb more quickly during exercise, potentially causing hypoglycemia in persons with type 1 diabetes. We develop a model that relates exercise-induced physiological changes to enhanced insulin-absorption (k) and glucose uptake (GU). Drawing on concepts of the microcirculation we derive a relationship that reveals that k and GU are mainly determined by two physiological parameters that characterize the tissue: the tissue perfusion rate (Q) and the capillary permeability surface area (PS). Independently measured values of Q and PS from the literature are used in the model to make predictions of k and GU. We compare these predictions to experimental observations of healthy and diabetic patients that are given a meal followed by rest or exercise. The experiments show that during exercise insulin concentrations significantly increase and that glucose levels fall rapidly. The model predictions are consistent with the experiments and show that increases in Q and PS directly increase k and GU. This mechanistic understanding provides a basis for handling exercise in control algorithms for an artificial pancreas. Now at University of British Columbia.

  13. 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

  14. 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.

  15. Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis.

    Science.gov (United States)

    Liu, T; Kishton, R J; Macintyre, A N; Gerriets, V A; Xiang, H; Liu, X; Abel, E D; Rizzieri, D; Locasale, J W; Rathmell, J C

    2014-10-16

    The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This metabolic program leads to high rates of glucose consumption through glycolysis with secretion of lactate even in the presence of oxygen. Identifying the limiting events in aerobic glycolysis and the response of cancer cells to metabolic inhibition is now essential to exploit this potential metabolic dependency. Here, we examine the role of glucose uptake and the glucose transporter Glut1 in the metabolism and metabolic stress response of BCR-Abl+ B-cell acute lymphoblastic leukemia cells (B-ALL). B-ALL cells were highly glycolytic and primary human B-ALL samples were dependent on glycolysis. We show B-ALL cells express multiple glucose transporters and conditional genetic deletion of Glut1 led to a partial loss of glucose uptake. This reduced glucose transport capacity, however, was sufficient to metabolically reprogram B-ALL cells to decrease anabolic and increase catabolic flux. Cell proliferation decreased and a limited degree of apoptosis was also observed. Importantly, Glut1-deficient B-ALL cells failed to accumulate in vivo and leukemic progression was suppressed by Glut1 deletion. Similarly, pharmacologic inhibition of aerobic glycolysis with moderate doses of 2-deoxyglucose (2-DG) slowed B-ALL cell proliferation, but extensive apoptosis only occurred at high doses. Nevertheless, 2-DG induced the pro-apoptotic protein Bim and sensitized B-ALL cells to the tyrosine kinase inhibitor Dasatinib in vivo. Together, these data show that despite expression of multiple glucose transporters, B-ALL cells are reliant on Glut1 to maintain aerobic glycolysis and anabolic metabolism. Further, partial inhibition of glucose metabolism is sufficient to sensitize cancer cells to specifically targeted therapies, suggesting

  16. Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects.

    Science.gov (United States)

    Ishibashi, Kenji; Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

    2017-01-01

    Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4-5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images.

  17. Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Mopuri, Ramgopal; Nagiah, Savania; Chuturgoon, Anil Amichund; Islam, Md Shahidul

    2017-08-02

    Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3). Experiment 1 examined the effects of increasing concentrations (2.5-20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals. Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals. Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

  18. The flavanone homoeriodictyol increases SGLT-1-mediated glucose uptake but decreases serotonin release in differentiated Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Barbara Lieder

    Full Text Available Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM. The glucose uptake stimulating effect was sensitive to phloridzin, but not to phloretin, indicating an involvement of the sodium-coupled glucose transporter SGLT-1, but not of sodium-independent glucose transporters (GLUT. In addition, in contrast to the increased extracellular serotonin levels by stimulation with 500 mM D-(+-glucose, treatment with 100 μM homoeriodictyol decreased serotonin release by -48.8 ± 7.57% in Caco-2 cells via a phloridzin-sensitive signaling pathway. Extracellular serotonin levels were also reduced by -57.1 ± 5.43% after application of 0.01 μM homoeriodictyol to human neural SH-SY5Y cells. In conclusion, we demonstrate that homoeriodictyol affects both the glucose metabolism and the serotonin system in Caco-2 cells via a SGLT-1-meditated pathway. Furthermore, the results presented here support the usage of Caco-2 cells as a model for peripheral serotonin release. Further investigations may address the value of homoeriodictyol in the treatment of anorexia and malnutrition through the targeting of SGLT-1.

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

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: Objective: To determine whether the cerebral metabolism in various regions of the normal human brain differs from those of cancer patients in aging by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples so called 'normal group' (ranging 21 to 88; mean age+/-SD: 50+/-14) and 290 cancer patients called 'cancer group' (ranging 21 to 85; mean age+/-SD: 54+/-14) who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They were selected with: (i) absence of clear focal brain lesions (epilepsy, cerebrovascular diseases etc.); (ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes; (iii) absence of psychiatric disorders and abuse of drugs and alcohol;( iiii) cancer patients were diagnosed definitely of variable cancers except brain cancer or brain metastasis. Both groups were sub grouped into six with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose are matched. All 12 subgroups were compared to the subgroup of normal 31-40 years old called 'control subgroup' (84 samples; mean age+/-SD: 37.15+/- 2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later; their brains were scanned for 10 minutes. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2). The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three dimensional localized by MNI Space utility (MSU) software. Results:1.With increasing of age interval, similar hypometabolic brain areas are detected in both 'normal group' and 'cancer group', they are mainly in the cortical structures such as bilateral prefrontal cortex (BA9), superior temporal gyrus (BA22), parietal cortex (inferior parietal lobule and precuneus(BA40), insula (BA13

  20. Abnormality of cerebral cortical glucose metabolism in temporal lobe epilepsy with cognitive function impairment

    International Nuclear Information System (INIS)

    Bang-Hung Yang; Tsung-Szu Yeh; Tung-Ping Su; Jyh-Cheng Chen; Ren-Shyan Liu

    2004-01-01

    Objective: People with epilepsy commonly report having problems with their memory. Many indicate that memory difficulties significantly hinder their functioning at work, in school, and at home. Besides, some studies have reported that memory performance as a prognostic factor is of most value in patients with risk of refractory epilepsy and when used in a multidisciplinary setting. However, the cerebral cortical areas involving memory impairment in epilepsy is still unknown. The purpose of this study was to access changes of cerebral glucose metabolism of epilepsy patients using [F-18] fluorodeoxyglucose positron emission tomography (FDG PET). Method: Nine temporal lobe epilepsy patients were studied. Each patient was confirmed with lesions in right mesial temporal lobe by MRI, PET and EEG. Serial cognition function tests were performed. Regional cerebral glucose metabolism (rCMRglc) was measured by PET at 45 minutes after injection of 370 MBq of FDG. Parametric images were generated by grand mean scaling each scan to 50. The images were then transformed into standard stereotactic space. Statistical parametric mapping (SPM2) was applied to find the correlations between verbal memory, figure memory, perception intelligent quotation (PIQ) and rCMRglc in epilepsy patients. The changes of rCMRglc were significant if corrected p value was less than 0.05. Results: There was no significant relationship between figure memory score and verbal memory score. FDG-PET scan showed changes of rCMRglc positive related with verbal memory score in precentral gyms of right frontal lobe (Brodmann area 4, corrected p < 0.001, voxel size 240) and cingulated gyms of right limbic lobe (Brodmann area 32, corrected p=0.002, voxel size 143). No negative relationship was demonstrable between verbal memory and rCMRglc in this study. Besides, significanfiy positive correlation between figure memory was shown in cuneus of right occipital lobe (Brodmann area 18, corrected p < 0.001, voxel size

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-07-01

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

  2. Novel Benzoxazine-Based Aglycones Block Glucose Uptake In Vivo by Inhibiting Glycosidases

    Science.gov (United States)

    Jagadish, Swamy; Paricharak, Shardul; Hemshekhar, Mahadevappa; Mason, Daniel; Kemparaju, Kempaiah; Girish, Kesturu S.; Basappa; Bender, Andreas; Rangappa, Kanchugarakoppal S.

    2014-01-01

    Glycoside hydrolases catalyze the selective hydrolysis of glycosidic bonds in oligosaccharides, polysaccharides, and their conjugates. β-glucosidases occur in all domains of living organisms and constitute a major group among glycoside hydrolases. On the other hand, the benzoxazinoids occur in living systems and act as stable β-glucosides, such as 2-(2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one)-β-D-gluco-pyranose, which hydrolyse to an aglycone DIMBOA. Here, we synthesized the library of novel 1,3-benzoxazine scaffold based aglycones by using 2-aminobenzyl alcohols and aldehydes from one-pot reaction in a chloroacetic acid catalytic system via aerobic oxidative synthesis. Among the synthesized benzoxazines, 4-(7-chloro-2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol (compound 7) exhibit significant inhibition towards glucosidase compared to acarbose, with a IC50 value of 11.5 µM. Based upon results generated by in silico target prediction algorithms (Naïve Bayesian classifier), these aglycones potentially target the additional sodium/glucose cotransporter 1 (where a log likelihood score of 2.70 was observed). Furthermore, the in vitro glucosidase activity was correlated with the in silico docking results, with a high docking score for the aglycones towards the substrate binding site of glycosidase. Evidently, the in vitro and in vivo experiments clearly suggest an anti-hyperglycemic effect via glucose uptake inhibition by 4-(7-chloro-2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol in the starved rat model. These synthetic aglycones could constitute a novel pharmacological approach for the treatment, or re-enforcement of existing treatments, of type 2 diabetes and associated secondary complications. PMID:25047583

  3. Novel benzoxazine-based aglycones block glucose uptake in vivo by inhibiting glycosidases.

    Directory of Open Access Journals (Sweden)

    Hanumantharayappa Bharathkumar

    Full Text Available Glycoside hydrolases catalyze the selective hydrolysis of glycosidic bonds in oligosaccharides, polysaccharides, and their conjugates. β-glucosidases occur in all domains of living organisms and constitute a major group among glycoside hydrolases. On the other hand, the benzoxazinoids occur in living systems and act as stable β-glucosides, such as 2-(2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H-one-β-D-gluco-pyranose, which hydrolyse to an aglycone DIMBOA. Here, we synthesized the library of novel 1,3-benzoxazine scaffold based aglycones by using 2-aminobenzyl alcohols and aldehydes from one-pot reaction in a chloroacetic acid catalytic system via aerobic oxidative synthesis. Among the synthesized benzoxazines, 4-(7-chloro-2,4-dihydro-1H-benzo[d][1,3]oxazin-2-ylphenol (compound 7 exhibit significant inhibition towards glucosidase compared to acarbose, with a IC50 value of 11.5 µM. Based upon results generated by in silico target prediction algorithms (Naïve Bayesian classifier, these aglycones potentially target the additional sodium/glucose cotransporter 1 (where a log likelihood score of 2.70 was observed. Furthermore, the in vitro glucosidase activity was correlated with the in silico docking results, with a high docking score for the aglycones towards the substrate binding site of glycosidase. Evidently, the in vitro and in vivo experiments clearly suggest an anti-hyperglycemic effect via glucose uptake inhibition by 4-(7-chloro-2,4-dihydro-1H-benzo[d][1,3]oxazin-2-ylphenol in the starved rat model. These synthetic aglycones could constitute a novel pharmacological approach for the treatment, or re-enforcement of existing treatments, of type 2 diabetes and associated secondary complications.

  4. Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise

    DEFF Research Database (Denmark)

    Sylow, Lykke; Møller, Lisbeth; Kleinert, Maximilian

    2017-01-01

    Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin-resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake...... deletion of Rac1. Muscle-specific knockout (mKO) of Rac1, a kinasedead a2 AMPK (a2KD), and double knockout (KO) of b1 and b2 AMPK subunits (b1b2 KO) each partially decreased contraction-stimulated glucose transport in mouse soleus and extensor digitorum longus (EDL) muscle. Interestingly, when...... pharmacological Rac1 inhibition was combined with either AMPK b1b2 KO or a2KD, contraction-stimulated glucose transport was almost completely inhibited. Importantly, a2KD+Rac1 mKO double-transgenic mice also displayed severely impaired contraction-stimulated glucose transport, whereas exercise-stimulated glucose...

  5. 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.

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

    International Nuclear Information System (INIS)

    Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

    1989-01-01

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

  7. Rapid uptake of glucose and lactate, and not hypoxia, induces apoptosis in three-dimensional tumor tissue culture.

    Science.gov (United States)

    Kasinskas, Rachel W; Venkatasubramanian, Raja; Forbes, Neil S

    2014-04-01

    The spatial arrangement of cellular metabolism in tumor tissue critically affects the treatment of cancer. However, little is known about how diffusion and cellular uptake relate to intracellular metabolism and cell death in three dimensions. To quantify these mechanisms, fluorescent microscopy and multicellular tumor cylindroids were used to measure pH and oxygen profiles, and quantify the distribution of viable, apoptotic and necrotic cells. Spheroid dissociation, enzymatic analysis, and mass spectrometry were used to measure concentration profiles of glucose, lactate and glutamine. A mathematical model was used to integrate these measurements and calculate metabolic rate parameters. It was found that large cylindroids, >500 μm in diameter, contained apoptotic and necrotic cells, whereas small cylindroids contained apoptotic but not necrotic cells. The center of cylindroids was found to be acidic but not hypoxic. From the edge to the center, concentrations of glucose, lactate and glutamine decreased rapidly. Throughout the cell masses lactate was consumed and not produced. These measurements indicate that apoptosis was the primary mechanism of cell death; acidity was not caused by lactic acid; and cell death was caused by depletion of carbon sources and not hypoxia. The mathematical model showed that the transporter enzymes for glucose and lactate were not saturated; oxygen uptake was limited by intracellular metabolism; and oxygen uptake was not limited by membrane-transport or diffusion. Unsaturated transmembrane uptake may be the cause of both proliferative and apoptotic regimes in cancer. These results suggest that transporter enzymes are excellent targets for treating well oxygenated tumors.

  8. Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats.

    Science.gov (United States)

    Cheng, Tse-Chou; Lin, Chian-Shiung; Hsu, Chih-Chieh; Chen, Li-Jen; Cheng, Kai-Chun; Cheng, Juei-Tang

    2009-11-20

    Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway.

  9. Changes in cerebral glucose metabolism in patients with posttraumatic cognitive impairment after memantine therapy. A preliminary study

    International Nuclear Information System (INIS)

    Kim, Yong-Wook; Shin, Ji-Cheol; An, Young-Sil

    2010-01-01

    The objective of this study was to investigate the changes in cerebral glucose metabolism in patients with posttraumatic cognitive impairment after memantine therapy. We performed serial F-18 fluorodeoxyglucose positron emission tomography studies before and after memantine therapy (20 mg per day) on 17 patients with posttraumatic cognitive impairment using statistical parametric mapping analysis. In addition, covariance analysis was performed to identify regions, where changes in regional cerebral glucose metabolism correlated significantly with increased Mini-Mental Status Examination scores. Statistical parametric mapping analysis demonstrated that, compared with baseline, significantly increased cerebral glucose metabolism occurred in both inferior, middle and superior frontal gyri, both angular gyri, both precuneus, the right middle cingulum, the left inferior parietal lobule, the left fusiform gyrus, the left precentral gyrus, the left paracentral lobule, and the left lingual gyrus after memantine therapy (P uncorrected uncorrected corrected <0.0001). Our findings indicate that the prefrontal and the parietal association cortices may be the relevant structures for the pharmacological response to memantine therapy in patients with posttraumatic cognitive impairment. (author)

  10. Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization

    International Nuclear Information System (INIS)

    Blomqvist, G.; Widen, L.; Hellstrand, E.; Gutniak, M.; Grill, V.

    1991-01-01

    The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using D-glucose 11 C(ul) as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62±19 (mean±SEM) μmol hg -1 min -1 , and the half-saturation constant was found to be 4.1±3.2 mM. (orig.)

  11. AKT inhibitors promote cell death in cervical cancer through disruption of mTOR signaling and glucose uptake.

    Directory of Open Access Journals (Sweden)

    Ramachandran Rashmi

    Full Text Available PI3K/AKT pathway alterations are associated with incomplete response to chemoradiation in human cervical cancer. This study was performed to test for mutations in the PI3K pathway and to evaluate the effects of AKT inhibitors on glucose uptake and cell viability.Mutational analysis of DNA from 140 pretreatment tumor biopsies and 8 human cervical cancer cell lines was performed. C33A cells (PIK3CAR88Q and PTENR233* were treated with increasing concentrations of two allosteric AKT inhibitors (SC-66 and MK-2206 with or without the glucose analogue 2-deoxyglucose (2-DG. Cell viability and activation status of the AKT/mTOR pathway were determined in response to the treatment. Glucose uptake was evaluated by incubation with 18F-fluorodeoxyglucose (FDG. Cell migration was assessed by scratch assay.Activating PIK3CA (E545K, E542K and inactivating PTEN (R233* mutations were identified in human cervical cancer. SC-66 effectively inhibited AKT, mTOR and mTOR substrates in C33A cells. SC-66 inhibited glucose uptake via reduced delivery of Glut1 and Glut4 to the cell membrane. SC-66 (1 µg/ml-56% and MK-2206 (30 µM-49% treatment decreased cell viability through a non-apoptotic mechanism. Decreases in cell viability were enhanced when AKT inhibitors were combined with 2-DG. The scratch assay showed a substantial reduction in cell migration upon SC-66 treatment.The mutational spectrum of the PI3K/AKT pathway in cervical cancer is complex. AKT inhibitors effectively block mTORC1/2, decrease glucose uptake, glycolysis, and decrease cell viability in vitro. These results suggest that AKT inhibitors may improve response to chemoradiation in cervical cancer.

  12. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease.

  13. 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

    2017-01-01

    ]glucose in slices from cerebral cortex and hippocampus revealed no significant regional differences regarding glycolytic or total TCA cycle activities. On the contrary, results from the incubations with [1,2-(13)C]acetate suggest a higher capacity of the astrocytic TCA cycle in hippocampus compared to cerebral...

  14. Betulinic acid is a PPARγ antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis.

    Science.gov (United States)

    Brusotti, Gloria; Montanari, Roberta; Capelli, Davide; Cattaneo, Giulia; Laghezza, Antonio; Tortorella, Paolo; Loiodice, Fulvio; Peiretti, Franck; Bonardo, Bernadette; Paiardini, Alessandro; Calleri, Enrica; Pochetti, Giorgio

    2017-07-18

    PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, and they serve as an alternative treatment for metabolic diseases. In this work, an affinity-based bioassay was found to be effective for selecting PPAR ligands from the dried extract of an African plant (Diospyros bipindensis). Among the ligands, we identified betulinic acid (BA), a compound already known for its anti-inflammatory, anti-tumour and antidiabetic properties, as a PPARγ and PPARα antagonist. Cell differentiation assays showed that BA inhibits adipogenesis and promotes osteogenesis; either down-regulates or does not affect the expression of a series of adipogenic markers; and up-regulates the expression of osteogenic markers. Moreover, BA increases basal glucose uptake in 3T3-L1 adipocytes. The crystal structure of the complex of BA with PPARγ sheds light, at the molecular level, on the mechanism by which BA antagonizes PPARγ, and indicates a unique binding mode of this antagonist type. The results of this study show that the natural compound BA could be an interesting and safe candidate for the treatment of type 2 diabetes and bone diseases.

  15. Uptake and localization of 3H-2 deoxy-D-glucose by retinal photoreceptors

    International Nuclear Information System (INIS)

    Witkovsky, P.; Yang, C.Y.

    1982-01-01

    Following dark incubation of isolated retinas of Xenopus laevis in Ringer solution supplemented with 3H-2-Deoxy-D-glucose (2DG), virtually all of the uptake of the label was by the inner segments and synaptic bases of the photoreceptor cells. Autoradiographs prepared from conventionally fixed tissue showed the same cellular distribution of label as those prepared from identically incubated, unfixed, freeze-dried retinas. However, fixation removed about 77% of the total counts. This fixation-labile, soluble fraction was identified as being primarily 2DG-6 phosphate by thin-layer chromatography. The remaining insoluble fraction corresponded in distribution to glycogen grains. In cones, glycogen is stored primarily in the paraboloid, whereas in rods it is distributed throughout the inner segment and synaptic base. EM autoradiographs illustrated that these were the sites over which fixation-resistant 2DG label was localized. Measurements of radioactivity associated with extracts of retinal glycogen following 2DG incubation demonstrated that a disproportionately high fraction of total counts were associated with the glycogen fraction. We conclude that in the amphibian retina 2DG may be incorporated into glycogen

  16. Polyacetylenes from carrots (Daucus carota) improve glucose uptake in vitro in adipocytes and myotubes.

    Science.gov (United States)

    El-Houri, Rime B; Kotowska, Dorota; Christensen, Kathrine B; Bhattacharya, Sumangala; Oksbjerg, Niels; Wolber, Gerhard; Kristiansen, Karsten; Christensen, Lars P

    2015-07-01

    A dichloromethane (DCM) extract of carrot roots was found to stimulate insulin-dependent glucose uptake (GU) in adipocytes in a dose dependent manner. Bioassay-guided fractionation of the DCM extract resulted in the isolation of the polyacetylenes falcarinol and falcarindiol. Both polyacetylenes were able to significantly stimulate basal and/or insulin-dependent GU in 3T3-L1 adipocytes and porcine myotube cell cultures in a dose-dependent manner. Falcarindiol increased peroxisome proliferator-activated receptor (PPAR)γ-mediated transactivation significantly at concentrations of 3, 10 and 30 μM, while PPARγ-mediated transactivation by falcarinol was only observed at 10 μM. Docking studies accordingly indicated that falcarindiol binds to the ligand binding domain of PPARγ with higher affinity than falcarinol and that both polyacetylenes exhibit characteristics of PPARγ partial agonists. Falcarinol was shown to inhibit adipocyte differentiation as evident by gene expression studies and Oil Red O staining, whereas falcarindiol did not inhibit adipocyte differentiation, which indicates that these polyacetylenes have distinct modes of action. The results of the present study suggest that falcarinol and falcarindiol may represent scaffolds for novel partial PPARγ agonists with possible antidiabetic properties.

  17. Effects of sciatic nerve transection on glucose uptake in the presence and absence of lactate in the frog dorsal root ganglia and spinal cord

    Directory of Open Access Journals (Sweden)

    F Rigon

    Full Text Available Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT, which mimics the clinical symptoms of “phantom limb”, a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  19. Acupuncture regulates the glucose metabolism in cerebral functional regions in chronic stage ischemic stroke patients---a PET-CT cerebral functional imaging study

    Directory of Open Access Journals (Sweden)

    Huang Yong

    2012-06-01

    Full Text Available Abstract Background Acupuncture has been applied to aid in the recovery of post-stroke patients, but its mechanism is unclear. This study aims to analyze the relationship between acupuncture and glucose metabolism in cerebral functional regions in post-stroke patients using 18 FDG PET-CT techniques. Forty-three ischemic stroke patients were randomly divided into 5 groups: the Waiguan (TE5 needling group, the TE5 sham needling group, the sham point needling group, the sham point sham needling group and the non-needling group. Cerebral functional images of all patients were then acquired using PET-CT scans and processed by SPM2 software. Results Compared with the non-needling group, sham needling at TE5 and needling/sham needling at the sham point did not activate cerebral areas. However, needling at TE5 resulted in the activation of Brodmann Area (BA 30. Needling/sham needling at TE5 and needling at the sham point did not deactivate any cerebral areas, whereas sham needling at the sham point led to deactivation in BA6. Compared with sham needling at TE5, needling at TE5 activated BA13, 19 and 47 and did not deactivate any areas. Compared with needling at the sham point, needling at TE5 had no associated activation but a deactivating effect on BA9. Conclusion Needling at TE5 had a regulating effect on cerebral functional areas shown by PET-CT, and this may relate to its impact on the recovery of post-stroke patients.

  20. Carnosic acid stimulates glucose uptake in skeletal muscle cells via a PME-1/PP2A/PKB signalling axis.

    Science.gov (United States)

    Lipina, Christopher; Hundal, Harinder S

    2014-11-01

    Carnosic acid (CA) is a major constituent of the labiate herbal plant Rosemary (Rosmarinus officinalis), which has been shown to exhibit a number of beneficial health properties. In particular, recently there has been growing interest into the anti-obesity effects conveyed by CA, including its ability to counteract obesity-associated hyperglycaemia and insulin resistance. However, the mechanisms underlying its anti-diabetic responses are not fully understood. In this study, we hypothesized that CA may act to improve glycaemic status through enhancing peripheral glucose clearance. Herein, we demonstrate that CA acts to mimic the metabolic actions of insulin by directly stimulating glucose uptake in rat skeletal L6 myotubes, concomitant with increased translocation of the GLUT4 glucose transporter to the plasma membrane. Mechanistically, CA-induced glucose transport was found to be dependent on protein kinase B (PKB/Akt) but not AMPK, despite both kinases being activated by CA. Crucially, in accordance with its ability to activate PKB and stimulate glucose uptake, we show that CA conveys these effects through a pathway involving PME-1 (protein phosphatase methylesterase-1), a key negative regulator of the serine/threonine phosphatase PP2A (protein phosphatase 2A). Herein, we demonstrate that CA promotes PME-1 mediated demethylation of the PP2A catalytic subunit leading to its suppressed activity, and in doing so, alleviates the repressive action of PP2A towards PKB. Collectively, our findings provide new insight into how CA may improve glucose homeostasis through enhancing peripheral glucose clearance in tissues such as skeletal muscle through a PME-1/PP2A/PKB signalling axis, thereby mitigating pathological effects associated with the hyperglycaemic state. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway.

    Science.gov (United States)

    Lo, Hsin-Yi; Ho, Tin-Yun; Li, Chia-Cheng; Chen, Jaw-Chyun; Liu, Jau-Jin; Hsiang, Chien-Yun

    2014-09-10

    Diabetes, a common metabolic disorder, is characterized by hyperglycemia. Insulin is the principal mediator of glucose homeostasis. In a previous study, we identified a trypsin inhibitor, named Momordica charantia insulin receptor (IR)-binding protein (mcIRBP) in this study, that might interact with IR. The physical and functional interactions between mcIRBP and IR were clearly analyzed in the present study. Photo-cross-linking coupled with mass spectrometry showed that three regions (17-21, 34-40, and 59-66 residues) located on mcIRBP physically interacted with leucine-rich repeat domain and cysteine-rich region of IR. IR-binding assay showed that the binding behavior of mcIRBP and insulin displayed a cooperative manner. After binding to IR, mcIRBP activated the kinase activity of IR by (5.87 ± 0.45)-fold, increased the amount of phospho-IR protein by (1.31 ± 0.03)-fold, affected phosphoinositide-3-kinase/Akt pathways, and consequently stimulated the uptake of glucose in 3T3-L1 cells by (1.36 ± 0.12)-fold. Intraperitoneal injection of 2.5 nmol/kg mcIRBP significantly decreased the blood glucose levels by 20.9 ± 3.2% and 10.8 ± 3.6% in normal and diabetic mice, respectively. Microarray analysis showed that mcIRBP affected genes involved in insulin signaling transduction pathway in mice. In conclusion, our findings suggest that mcIRBP is a novel IRBP that binds to sites different from the insulin-binding sites on IR and stimulates both the glucose uptake in cells and the glucose clearance in mice.

  2. Magnesium Affects Poly(3-hydroxybutyrate-co-4-hydroxybutyrate Content and Composition by Affecting Glucose Uptake in Delftia acidovorans

    Directory of Open Access Journals (Sweden)

    Lee, W. H.

    2007-01-01

    Full Text Available Precise control of polyhydroxyalkanoate (PHA composition is necessary in order to synthesize polymers with specific properties. Among the various types of PHA that have been identified, those that contain 4-hydroxybutyrate (4HB monomers are especially useful in the medical and pharmaceutical fields as absorbable biomaterial. In this study, we have investigated the effect of magnesium concentration on the biosynthesis of poly(3-hydroxybutyrate-co-4-hydroxybutyrate [P(3HB-co-4HB] by Delftia acidovorans DS-17. Our results show that, magnesium affects the copolymer content and composition by affecting glucose uptake from the culture medium. Higher concentrations of magnesium resulted in lower molar fractions of 3HB in the copolymer and reduced uptake of glucose. The results show for the first time that magnesium may be used to achieve fine control of biologically synthesized PHA copolymer composition.

  3. Original Research: Polyphenols extracted from grape powder induce lipogenesis and glucose uptake during differentiation of murine preadipocytes.

    Science.gov (United States)

    Torabi, Sheida; DiMarco, Nancy M

    2016-10-01

    Assessing the effects of grapes and grape powder extracted polyphenols on lipogenesis and glucose uptake in adipocytes may clarify the risk/benefit of recommending them to individuals with obesity and insulin resistance. We investigated the effect of grape powder extracted polyphenols (GPEP) on intracellular fat accumulation and glucose uptake during differentiation of 3T3-F442A preadipocytes. Total polyphenols were extracted and measured based on gallic acid equivalents (GAE). There were 2167 mg of GAE polyphenols in 100 g of grape powder. 3T3-F442A cells were incubated with GPEP, extracted from 125-500 µg GP/mL of media, until day 8 of differentiation when the cells were collected for different assays. AdipoRed™ assay and Oil Red O staining showed that GPEP induced, in a dose-dependent manner, an increase in intracellular triacylglycerol (TAG) content of adipocytes. Concomitantly, grape powder extracted polyphenols increased, in a dose-dependent manner, glucose uptake by 3T3-F442A cells, and there was a strong positive correlation between glucose uptake and the amount of TAG accumulation (r = 0.826, n = 24, P ≤ 0.001). No changes in cell viability was measured by Trypan Blue staining, suggesting that these effects were independent of cytotoxicity. Western-blot showed that GPEP upregulated protein level of glucose transport protein 4 (GLUT4), p-PKB/Akt, and p-AMPK in 3T3-F442A adipocytes. LY294002 (10 µmol/L), a phosphatidyl-inositol 3 kinase inhibitor (PI3K), reversed the effects of grape powder extracted polyphenols on cellular lipid content and glucose uptake. Furthermore, quantitative real-time polymerase chain reaction showed that GPEP increased mRNA expression of GLUT4, fatty acid synthase, lipoprotein lipase, adiponectin, and peroxisome proliferator-activated receptor γ, while it decreased mRNA expression of leptin and Insig-1. Our results indicate that GPEP may induce adipocyte differentiation via upregulation of GLUT4, PI3K and

  4. Modulation of adipogenesis and glucose uptake by Curcuma longa extract in 3T3L1 and L6 cell lines - An in vitro study

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    A. Prathapan

    2012-05-01

    Full Text Available Objective: To evaluate the effects of ethyl acetate extract of Curcuma longa against modulation of glucose uptake and adipogenesis in cell line models. Methods: We used 3T3L1 and L6 cells to investigate cytotoxicity, glucose uptake with 2-NBDG as probe and adipogenesis. All the analysis was done with flowcytometry. Results: The results showed that the extract did not possess any significant glucose uptake activity but it exhibited significant adipocyte differentiation potential. Conclusions: Ethyl acetate extract of Curcuma longa exhibits significant antiadipogenesis and can be used as an effective drug for the treatment of obesity and other associated complications.

  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...... to exhaustion (15.8 +/- 1.7 min; P carbohydrate was not substantiated...... and, consequently, exhaustive exercise involves a brain surplus carbohydrate uptake of a magnitude comparable with its glycogen content....

  6. Enhanced Glucose Uptake in Human Liver Cells and Inhibition of Carbohydrate Hydrolyzing Enzymes by Nordic Berry Extracts

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    Giang Thanh Thi Ho

    2017-10-01

    Full Text Available A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE and then purified by C-18 solid phase extraction (SPE. Among the ASE methanol extracts, black chokeberry, crowberry and elderberry extracts showed high stimulation of glucose uptake in HepG2 cells and also considerable inhibitory effect towards carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of phenolics, resulted in increased glucose uptake and enhanced inhibition of α-amylase and α-glucosidase compared to the ASE extracts. Crowberry and cloudberry were the most potent 15-lipoxygenase inhibitors, while bog whortleberry and lingonberry were the most active xanthine oxidase inhibitors. These results increase the value of these berries as a component of a healthy Nordic diet and have a potential benefit against diabetes.

  7. Relation of local cerebral metabolic rate of glucose to endocrine fluctuation around seizures

    International Nuclear Information System (INIS)

    Wang Mingfang; Sun Qiyin; Sun Aijun

    1999-01-01

    Objection: To probe into the relation of local cerebral metabolic rate of glucose (LCMRglc) to endocrine fluctuation around seizures. Methods: Serum prolactin (PRL), growth hormone (GH) and cortisol levels in 76 epileptic patients with unilobar epileptic focus were determined by radioimmunoassay (RIA) before and after seizures. Moreover, the patients were examined by 18 F-FDG PET imaging and the LCMRglc of epileptic foci was measured. Results: FDG metabolic level of epileptic foci right at the attack was relatively higher than that at interictal phase, and the serum PRL, GH and cortisol levels were significant higher after seizures. The serum PRL levels in 80.3% patients and the serum cortisol levels in 68.4% patients reached their peaks 15 min after seizure. The serum GH levels in 65.8% patients reached peaks at 30 min after seizure. The changes of hormone levels correlated significantly with the lengths of seizure free intervals (SFI) and with the types of seizures, but the changes of hormone levels were of no relation with the site and LCMRglc of epileptic foci. In 6 patients with absentia seizures, no significant increase was observed in LCMRglc (P > 0.05), nor in serum PRL and cortisol; the changes of GH were not related with the types of seizures. Also, the shorter the SFI was, and the lower the basal hormone levels were, and the less the postictal hormone levels increased especially the levels of GH and cortisol. conclusions: the serum PRL, GH, cortisol levels are significantly different before and after seizures, the hormone levels reached their peaks from 15 min to 30 min after seizures. The changes of postictal hormone levels are correlated significantly with the types of seizures and length of SFI, but the changes of hormone levels are not related with the site and FDG metabolism of epileptic foci

  8. Promotion of Glucose Uptake in C2C12 Myotubes by Cereal Flavone Tricin and Its Underlying Molecular Mechanism.

    Science.gov (United States)

    Kim, Sohyun; Go, Gwang-Woong; Imm, Jee-Young

    2017-05-17

    The effect of tricin, a methylated flavone widely distributed in cereals, on glucose uptake and the underlying molecular mechanism was investigated using C2C12 myotubes. Tricin significantly increased glucose uptake in C2C12 myotubes, regardless of the absence (1.4-fold at 20 μM) or presence (1.6-fold at 20 μM) of insulin. The GLUT4 expression on the plasma membrane was increased 1.6-fold after tricin treatment (20 μM) in the absence of insulin. Tricin treatment significantly activated the insulin-dependent cell signaling pathway, including the activation of insulin receptor substrate-1 (IRS1), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and AKT substrate of 160 kDa (AS160). The oral administration of tricin (64 and 160 mg kg -1 of body weight day -1 ) also significantly lowered blood glucose levels in glucose-loaded C57BL/6 mice (p < 0.05). These results suggest that tricin has great potential to be used as a functional agent for glycemic control.

  9. Functional analyse of GLUT1 and GLUT12 in glucose uptake in goat mammary gland epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qinghua Yu

    Full Text Available Glucose transport, mediated by glucose transporters, is necessary for mammary gland development and lactation. GLUT1 and GLUT12 could both be expressed in the pregnant and lactating mammary gland to participate in the glucose uptake process. In this study, the goat GLUT1 and GLUT12 genes were cloned from Saanen dairy goats and transfected into goat mammary gland epithelial cells to assess their biological functions and distributions. The results showed that both goat GLUT1 and GLUT12 had 12 predicted membrane-spanning helices. Goat GLUT1 and GLUT12 each influenced the mRNA expression of the other transporter and increased the glucose consumption and lactose yield in GLUT1- and GLUT12-transfected goat mammary gland epithelial cells, respectively. The overexpression of GLUT1 or GLUT12 also increased the expression of amino acid transporters SLC1A5, SLC3A2 and SLC7A5 and affected genes expressions in GMGE cells. Using immunofluorescence staining, GLUT1 was detected throughout the cytoplasm and localized to the Golgi apparatus around the nuclear membrane, whereas GLUT12 was mainly distributed in the perinuclear region and cytoplasm. This study contributes to the understanding of how GLUT1 and GLUT12 cooperate in the incorporation of nutrient uptake into mammary gland epithelial cells and the promotion of milk synthesis in the goat mammary gland during lactation.

  10. Comparative effect of lidocaine and bupivacaine on glucose uptake and lactate production in the perfused working rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Cronau, L.H. Jr.; Merin, R.G.; Aboulish, E.; Steenberg, M.L.; Maljorda, A.

    1986-03-01

    It has been suggested that at equivalent therapeutic concentrations, lidocaine and bupivacaine may have different cardiotoxic potency. In the isolated working rat heart preparation, the effect of a range of lidocaine and bupivacaine concentrations on glucose uptake and lactate production (LP) were observed. Insulin was added, 10 ..mu../L, to Ringer's solution containing /sup 3/H-labeled glucose to measure the glycolytic flux (GF). The effect of the local anesthetics on LP at the indicated concentrations were similar. Lidocaine appears to depress the glycolytic flux from exogenous glucose to a lesser degree. Bupivacaine, 10 mg/L, depresses VO/sub 2/ to a greater degree than does lidocaine, 40 mg/L.

  11. Diminished insulin-mediated forearm blood flow and muscle glucose uptake in young men with low birth weight

    DEFF Research Database (Denmark)

    Sonne, M P; Højbjerre, L; Alibegovic, A C

    2009-01-01

    with venous occlusion plethysmography and intra-arterial infusions of adenosine and acetylcholine, before and during a hyperinsulinemic isoglycemic clamp. RESULTS: Forearm blood flow response to systemic hyperinsulinemia was diminished in LBW compared to controls (p Fractional arteriovenous glucose...... extraction was similar, and consequently insulin-stimulated forearm glucose clearance was diminished in LBW compared with controls (0.8 +/- 0.09 vs. 1.4 +/- 0.36 ml x 100 ml(-1) x min(-1), respectively, p blood flow response to adenosine and acetylcholine with or without insulin stimulation...... did not differ between groups. Whole-body glucose uptake was lower in LBW than controls (8.7 +/- 0.5 and 9.1 +/- 0.6 mg x min(-1) x kg(-1) lean body mass); however, this was not significant. CONCLUSIONS: Forearm blood flow response to insulin is impaired in LBW, whereas the response to adenosine...

  12. Ibervillea sonorae (Cucurbitaceae) induces the glucose uptake in human adipocytes by activating a PI3K-independent pathway.

    Science.gov (United States)

    Zapata-Bustos, Rocio; Alonso-Castro, Angel Josabad; Gómez-Sánchez, Maricela; Salazar-Olivo, Luis A

    2014-03-28

    Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE). Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques. ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid. Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independent pathway and without proadipogenic effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. DiabetterTM Reduces Post Meal Hyperglycemia Via Enhancement Of Glucose Uptake Into Adipocytes And Muscles Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Shafii Khamis

    2014-01-01

    Currently, there are lots of herbal products available in local markets that are used for treatment of diabetes mellitus. Most of these products are not standardized and lack of efficacy and safety data. DiaBetterTM is one of the local herbal products that have been used for treatment of diabetes. This study was carried out to determine the efficacy of DiaBetterTM in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. Antihyperglycemic evaluation was done in normal and streptozotocin-induced diabetic rats at different prandial states and the antihyperglycemic mechanisms elucidation was carried out in muscle and adipocytes cells using glucose tracer method (2-deoxy-[1-3H]-glucose). The results showed that DiaBetterTM significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetterTM significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54-fold (p<0.01) and 1.46-fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetterTM was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity activity of DiaBetterTM was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetterTM suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that DiaBetterTM can be used as dietary adjunct for the treatment of type 2 diabetes mellitus which related to insulin resistance. (author)

  14. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B

    2011-01-01

    reduces neurogenesis and cerebral volume, impairs memory and increases the incidence of cerebral palsy. Cerebral effects of glucocorticoids in later childhood have been less thoroughly studied, but apparent brain atrophy, reduced size of limbic structures and neuropsychiatric symptoms have been reported....... Glucocortioids affect several cellular structures and functions, which may explain the observed adverse effects. Glucocorticoids can impair neuronal glucose uptake, decrease excitability, cause atrophy of dendrites, compromise development of myelin-producing oligodendrocytes and disturb important cellular...

  15. The effect of aniracetam on cerebral glucose metabolism in rats after lesioning of the basal forebrain measured by PET.

    Science.gov (United States)

    Ouchi, Y; Kakiuchi, T; Okada, H; Nishiyama, S; Tsukada, H

    1999-03-15

    To evaluate the effect of aniracetam, a potent modulator of the glutamatergic and cholinergic systems, on the altered cerebral glucose metabolism after lesioning of the basal forebrain, we measured the cerebral metabolic rate of glucose (CMRGlc) with positron emission tomography and the choline acetyltransferase (ChAT) activity in the frontal cortex of the lesioned rats after treating them with aniracetam. Continuous administration of aniracetam for 7 days after the surgery prevented CMRGlc reduction in the frontal cortex ipsilateral to the lesion while the lesioned rats without aniracetam showed significant CMRGlc reduction in the frontal cortex. The level of CMRGlc in the lesion-side basal forebrain was lower in all rats regardless of the aniracetam treatment. Biochemical studies showed that aniracetam did not alter the reduction in the frontal ChAT activity. These results showed that aniracetam prevents glucose metabolic reduction in the cholinergically denervated frontal cortex with little effect on the cortical cholinergic system. The present study suggested that a neurotransmitter system other than the cholinergic system, e.g. the glutamatergic system, plays a central role in the cortical metabolic recovery after lesioning of the basal forebrain.

  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

    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)...... evaluable and regional cerebral metabolic rate for glucose (rCMRglc) was estimated in nontumoral brain regions in 12 patients treated with surgery alone and 9 patients treated with both surgery and CRT. Furthermore 10 normal controls matched for age at examination were included. Patients treated with both...

  17. Involvement of Rac1 and the actin cytoskeleton in insulin- and contraction-stimulated intracellular signaling and glucose uptake in mature skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke

    to hyperinsulinemia and hyperglycemia. Blood glucose is taken up into skeletal muscle when glucose transporters move to the muscle cell surface. In muscle cells this process depends on the protein Rac1. Glucose uptake into skeletal muscle can also occur via insulin-independent mechanisms, such as during muscle...... understood. The aim of the current PhD was therefore to investigate the involvement of Rac1 and the actin cytoskeleton in the regulation of insulin- and contraction-stimulated glucose uptake in mature skeletal muscle. The central findings of this PhD thesis was that Rac1 was activated by both insulin...... and muscle contraction in mouse and human skeletal muscle. Most importantly, Rac1 was involved in the regulation of both insulin- and contraction-stimulated glucose uptake. Interestingly, Rac1 signaling was defective in skeletal muscle of insulin resistant obese and T2D human subjects as well as in obese...

  18. Evidence for the absence of cerebral glucose-6-phosphatase activity in glycogen storage disease type I (Von Gierke's disease)

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, M.E.; Mazziotta, J.C.; Hawkins, R.A.; Philippart, M.

    1981-01-01

    Glycogen storage disease type I (GSD-I) is characterized by a functional deficit in glucose-6-phosphatase that normally hydrolyzes glucose-6-PO/sub 4/ to glucose. This enzyme is primarily found in liver, kidney, and muscle but it is also present in brain, where it appears to participate in the regulation of cerebral tissue glucose. Since most neurological symptoms in GSD-I patients involve systemic hypoglycemia, previous reports have not examined possible deficiencies in phosphatase activity in the brain. Positron computed tomography, F-18-labeled 2-fluorodeoxyglucose (FDG) and a tracer kinetic model for FDG were used to measure the cortical plasma/tissue forward and reverse transport, phosphorylation and dephosphorylation rate constants, tissue/plasma concentration gradient, tissue concentration turnover rate for this competitive analog of glucose, and the cortical metabolic rates for glucose. Studies were carried out in age-matched normals (N = 13) and a single GSD-I patient. The dephosphorylation rate constant in the GSD-I patient was about one tenth the normal value indicating a low level of cerebral phosphatase activity. The other measured parameters were within normal limits except for the rate of glucose phosphorylation which reflected a cortical glucose metabolic rate one half the normal value. Since glucose transport and tissue glucose concentration was normal, the reduced cortical glucose metabolism probably results from the use of alternative substrates (..beta..-hydroxybutyrate and acetoacetate) which are consistently elevated in the plasma of GSD-I patients.

  19. Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

    Science.gov (United States)

    Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

    2017-09-01

    Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

  20. Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4.

    Science.gov (United States)

    Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V; Manjunath, Kirangadur; Viswanatha, Gollapalle L; Ashok, Godavarthi

    2014-12-01

    The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria (MFMC) on PPARγ (Peroxisome Proliferator Activated Receptor gamma) and GLUT-4 (Glucose transporter-4) with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL(-1) were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC (500 μg·mL(-1)) was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARγ gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide (CHX), which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARγ and GLUT-4 in vitro. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  1. Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise.

    Science.gov (United States)

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; D'Hulst, Gommaar; De Groote, Estelle; Schjerling, Peter; Steinberg, Gregory R; Jensen, Thomas E; Richter, Erik A

    2017-06-01

    Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin-resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake, but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss of function combined with either pharmacological inhibition or genetic deletion of Rac1.Muscle-specific knockout (mKO) of Rac1, a kinase-dead α2 AMPK (α2KD), and double knockout (KO) of β1 and β2 AMPK subunits (β1β2 KO) each partially decreased contraction-stimulated glucose transport in mouse soleus and extensor digitorum longus (EDL) muscle. Interestingly, when pharmacological Rac1 inhibition was combined with either AMPK β1β2 KO or α2KD, contraction-stimulated glucose transport was almost completely inhibited. Importantly, α2KD+Rac1 mKO double-transgenic mice also displayed severely impaired contraction-stimulated glucose transport, whereas exercise-stimulated glucose uptake in vivo was only partially reduced by Rac1 mKO with no additive effect of α2KD. It is concluded that Rac1 and AMPK together account for almost the entire ex vivo contraction response in muscle glucose transport, whereas only Rac1, but not α2 AMPK, regulates muscle glucose uptake during submaximal exercise in vivo. © 2017 by the American Diabetes Association.

  2. Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18

    International Nuclear Information System (INIS)

    Baxter, L.R. Jr.; Phelps, M.E.; Mazziotta, J.C.; Schwartz, J.M.; Gerner, R.H.; Selin, C.E.; Sumida, R.M.

    1985-01-01

    Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression

  3. Chronic reactive oxygen species exposure inhibits glucose uptake and causes insulin resistance in C2C12 myotubes.

    Science.gov (United States)

    Ding, Hongwen; Heng, Baoli; He, Wenfang; Shi, Liping; Lai, Caiyong; Xiao, Long; Ren, Haolin; Mo, Shijie; Su, Zexuan

    2016-09-16

    Reactive oxygen species (ROS) is an important regulator in cellular signaling transduction, and many previous studies have indicated that acute ROS stimulation improves insulin sensitivity in skeletal muscle. In the study, we found that chronic ROS treatment caused serious insulin resistance in C2C12 myotubes. Glucose uptake and consumption assay indicated that pretreatment with 80 μM H2O2 for 2 h inhibited insulin-stimulated glucose uptake in C2C12 myotubes, and the reason for it, is that chronic H2O2 treatment decreased insulin-induced glucose transporter 4 (GLUT4) translocation from cell plasma to cell membrane. Moreover, Akt2 phosphorylation depended on insulin was reduced in C2C12 myotubes of chronic H2O2 treatment. Together, this study provides further demonstration that chronic ROS stress is associated with insulin resistance of skeletal muscle in the progression of type 2 diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Selina Mäkinen

    2017-07-01

    Full Text Available Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pretreated with palmitate, oleate or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [3H]-2-deoxy-d-glucose, insulin signalling and activation of endoplasmic reticulum (ER stress by Western blotting, and mitochondrial reactive oxygen species (ROS production by fluorescent dye MitoSOX. Exposure of primary human myotubes to palmitate impaired insulin-stimulated Akt-Ser473, AS160 and GSK-3β phosphorylation, induced ER stress signalling target PERK and stress kinase JNK 54 kDa isoform. These effects were virtually abolished by concomitant exposure of palmitate-treated myotubes to oleate. However, an exposure to palmitate, oleate or their combination reduced insulin-stimulated glucose uptake. This was associated with increased mitochondrial ROS production in palmitate-treated myotubes co-incubated with oleate, and was alleviated by antioxidants MitoTempo and Tempol. Thus, metabolic and intracellular signalling events diverge in myotubes treated with palmitate and oleate. Exposure of human myotubes to excess fatty acids increases ROS production and induces insulin resistance.

  5. A-769662 activates AMPK {beta}1-containing complexes but induces glucose uptake through a PI3 kinase-dependent pathway in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Birk, Jesper Bratz; Hansen, Bo Falck

    2009-01-01

    uptake in skeletal muscle. We studied incubated soleus and extensor digitorum longus (EDL) muscles from 129S6/sv and C57BL/6 mice. Glucose uptake increased only in soleus from 129S6/sv when concentrations of A-769662 was 500 microM (~15%, p

  6. Effect of glucose on the activity and the kinetics of the maltose-uptake system and of α-glucosidase in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Görts, C.P.M.

    1969-01-01

    1. 1. During incubation of maltose-grown Saccharomyces cerevisiae cells in nutrient medium with glucose, the maltose-uptake system was almost completely inactivated within 90 min. During this deadaptation, the Km of the maltose-uptake system increased from 4 to 50 mM. 2. 2. The activity of

  7. Endothelin‐1 suppresses insulin‐stimulated Akt phosphorylation and glucose uptake via GPCR kinase 2 in skeletal muscle cells

    Science.gov (United States)

    Hoshi, Akimasa; Harada, Takuya; Higa, Tsunaki; Karki, Sarita; Terada, Koji; Higashi, Tsunehito; Mai, Yosuke; Nepal, Prabha; Mazaki, Yuichi; Miwa, Soichi

    2016-01-01

    Background and Purpose Endothelin‐1 (ET‐1) reduces insulin‐stimulated glucose uptake in skeletal muscle, inducing insulin resistance. Here, we have determined the molecular mechanisms underlying negative regulation by ET‐1 of insulin signalling. Experimental Approach We used the rat L6 skeletal muscle cells fully differentiated into myotubes. Changes in the phosphorylation of Akt was assessed by Western blotting. Effects of ET‐1 on insulin‐stimulated glucose uptake was assessed with [3H]‐2‐deoxy‐d‐glucose ([3H]2‐DG). The C‐terminus region of GPCR kinase 2 (GRK2‐ct), a dominant negative GRK2, was overexpressed in L6 cells using adenovirus‐mediated gene transfer. GRK2 expression was suppressed by transfection of the corresponding short‐interfering RNA (siRNA). Key Results In L6 myotubes, insulin elicited sustained Akt phosphorylation at Thr308 and Ser473, which was suppressed by ET‐1. The inhibitory effects of ET‐1 were prevented by treatment with a selective ETA receptor antagonist and a Gq protein inhibitor, overexpression of GRK2‐ct and knockdown of GRK2. Insulin increased [3H]2‐DG uptake rate in a concentration‐dependent manner. ET‐1 noncompetitively antagonized insulin‐stimulated [3H]2‐DG uptake. Blockade of ETA receptors, overexpression of GRK2‐ct and knockdown of GRK2 prevented the ET‐1‐induced suppression of insulin‐stimulated [3H]2‐DG uptake. In L6 myotubes overexpressing FLAG‐tagged GRK2, ET‐1 facilitated the interaction of endogenous Akt with FLAG‐GRK2. Conclusions and Implications Activation of ETA receptors with ET‐1 suppressed insulin‐induced Akt phosphorylation at Thr308 and Ser473 and [3H]2‐DG uptake in a GRK2‐dependent manner in skeletal muscle cells. These findings suggest that ETA receptors and GRK2 are potential targets for overcoming insulin resistance. PMID:26660861

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

    International Nuclear Information System (INIS)

    Toyama, H.; Uemura, K.; Kanekiyo, S.; Ishii, K.; Ishii, K.

    2002-01-01

    Aim: The purpose of this paper is to estimate a correlation between the extent of atrophy and the decline in the brain function measured with PET study among the patients with Alzheimer's disease by each brain lobe. Materials and Methods: Two groups, the normal controls (male: 8, female: 22 age: 62.4±4.9) and the patients with Alzheimer's disease (male: 6, female: 24, age: 65.9±7.2) participated in this study. The extent of atrophy was evaluated from the extracted gyrus on 2D-projection magnetic resonance imaging (MRI) and the cerebral cortical glucose metabolism was assessed on 2D-projection positron emission tomography (PET) image, and then a relationship between the cerebral atrophy and the function was evaluated by each brain lobe extracted automatically. 2D-projection of PET and MR images were made by means of the Mollweide method which keeps the area of the brain surface. In order to extract brain lobes from each subject automatically, the bitmap with different value by each brain lobe was made from a standard brain image and was automatically transformed to match each subject's brain image by using SPM99. A correlation image was generated between 2D-projection images of glucose metabolism and the area of the sulcus and the gyrus extracted from the correlation between MR and PET images clustered by K-means method. Results: The glucose metabolism of Alzheimer's disease was lower than that of normal control subjects at the frontal, parietal, and temporal lobes with the same extent of atrophy as that of the normal. There was high correlation between the area of gyrus and the glucose metabolism, and the correlation tendency of the Alzheimer's disease was steeper than that of the normal control at the parietal lobe. Conclusions: Combined analysis of regional morphology and function may be useful to distinguish pathological process such as early stage of Alzheimer's disease from normal physiological aging

  9. Photoactivation of GLUT4 translocation promotes glucose uptake via PI3-K/Akt2 signaling in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Lei Huang

    2014-05-01

    Full Text Available Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes. Dysfunction of PI-3K/Akt signaling was involved in insulin resistance. Glucose transporter 4 (GLUT4 is a key factor for glucose uptake in muscle and adipose tissues, which is closely regulated by PI-3K/Akt signaling in response to insulin treatment. Low-power laser irradiation (LPLI has been shown to regulate various physiological processes and induce the synthesis or release of multiple molecules such as growth factors, which (especially red and near infrared light is mainly through the activation of mitochondrial respiratory chain and the initiation of intracellular signaling pathways. Nevertheless, it is unclear whether LPLI could promote glucose uptake through activation of PI-3K/Akt/GLUT4 signaling in 3T3L-1 adipocytes. In this study, we investigated how LPLI promoted glucose uptake through activation of PI-3K/Akt/GLUT4 signaling pathway. Here, we showed that GLUT4 was localized to the Golgi apparatus and translocated from cytoplasm to cytomembrane upon LPLI treatment in 3T3L-1 adipocytes, which enhanced glucose uptake. Moreover, we found that glucose uptake was mediated by the PI3-K/Akt2 signaling, but not Akt1 upon LPLI treatment with Akt isoforms gene silence and PI3-K/Akt inhibitors. Collectively, our results indicate that PI3-K/Akt2/GLUT4 signaling act as the key regulators for improvement of glucose uptake under LPLI treatment in 3T3L-1 adipocytes. More importantly, our findings suggest that activation of PI3-K/Akt2/GLUT4 signaling by LPLI may provide guidance in practical applications for promotion of glucose uptake in insulin-resistant adipose tissue.

  10. Enhancement of glucose uptake in skeletal muscle L6 cells and insulin secretion in pancreatic hamster-insulinoma-transfected cells by application of non-thermal plasma jet

    Science.gov (United States)

    Kumar, Naresh; Kaushik, Nagendra K.; Park, Gyungsoon; Choi, Eun H.; Uhm, Han S.

    2013-11-01

    Type-II diabetes Mellitus is characterized by defects in insulin action on peripheral tissues, such as skeletal muscle, adipose tissue, and liver and pancreatic beta cells. Since the skeletal muscle accounts for approximately 75% of insulin-stimulated glucose-uptake in our body, impaired insulin secretion from defected beta cell plays a major role in the afflicted glucose homoeostasis. It was shown that the intracellular reactive oxygen species and nitric oxide level was increased by non-thermal-plasma treatment in ambient air. These increased intracellular reactive species may enhance glucose uptake and insulin secretion through the activation of intracellular calcium (Ca+) and cAMP production.

  11. Clinically relevant strategies for lowering cardiomyocyte glucose uptake for {sup 18}F-FDG imaging of myocardial inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Thackeray, James T.; Bankstahl, Jens P.; Bengel, Frank M. [Hanover Medical School, Department of Nuclear Medicine, Hanover (Germany); Wang, Yong; Wollert, Kai C. [Hanover Medical School, Department of Cardiology and Angiology, Hanover (Germany)

    2015-04-01

    Myocardial inflammation is an emerging target for novel therapies and thus for molecular imaging. Positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG) has been employed, but requires an approach for suppression of cardiomyocyte uptake. We tested clinically viable strategies for their suitability in mouse models in order to optimize preclinical imaging protocols. C57BL/6 mice (n = 56) underwent FDG PET under various conditions. In healthy animals, the effect of low-dose (5 units/kg) or high-dose (500 units/kg, 15 min prior) intravenous heparin, extended fasting (18 h) and the impact of conscious injection with limited, late application of isoflurane anaesthesia after 40 min of conscious uptake were examined in comparison to ketamine/xylazine anaesthesia. Conscious injection/uptake strategies were further evaluated at 3 days after permanent coronary artery occlusion. Under continuous isoflurane anaesthesia, neither heparin administration nor extended fasting significantly impacted myocardial {sup 18}F-FDG accumulation. Injection with 40 min uptake in awake mice resulted in a marked reduction of global myocardial {sup 18}F-FDG uptake compared to standard isoflurane anaesthesia (5.7 ± 1.1 %ID/g vs 30.2 ± 7.9 %ID/g, p < 0.01). Addition of heparin and fasting further reduced uptake compared to conscious injection alone (3.8 ± 1.5 %ID/g, p < 0.01) similar to ketamine/xylazine (2.4 ± 2.2 %ID/g, p < 0.001). In the inflammatory phase, 3 days after myocardial infarction, conscious injection/uptake with and without heparin/fasting identified a marked increase in myocardial {sup 18}F-FDG accumulation that was similar to that observed under ketamine/xylazine. Continuous isoflurane anaesthesia obscures any suppressive effect of heparin or fasting on cardiomyocyte glucose utilization. Conscious injection of FDG in rodents significantly reduces cardiomyocyte uptake and enables further suppression by heparin and fasting, similar to clinical observations. In

  12. Effects of melatonin on 2-deoxy-[1-14C]glucose uptake within rat suprachiasmatic nucleus

    International Nuclear Information System (INIS)

    Cassone, V.M.; Roberts, M.H.; Moore, R.Y.

    1988-01-01

    Previously, we have demonstrated that metabolic activity, shown by autoradiographic determination of 2-deoxy-[1- 14 C]glucose (2-DG) uptake, within the rat hypothalamic suprachiasmatic nuclei (SCN) was inhibited by subcutaneous injection of 1 mg/kg melatonin. To determine whether this effect was specific to a particular time of day, the effects of melatonin on 2-DG uptake were studied in several hypothalamic areas, including the SCN, supraoptic nuclei (SON), lateral hypothalamic area (LHA), and anterior hypothalamic area (AHA) every 4 h throughout the circadian day. In a second experiment, the effects of different melatonin doses were studied at the time of day at which melatonin had its maximal effect to determine the dose-response relationship of melatonin-induced inhibition of SCN 2-DG uptake. The data indicate that melatonin inhibited 2-DG uptake in the SCN alone at one time of day, primarily at circadian time (CT) 6 and CT10, 2-6 h before subjective dusk, and secondarily at CT22, just before subjective dawn. This effect was dose dependent with a 50% effective dose of 1.49 +/- 2.30 micrograms/kg. The temporal and dose-response characteristics of these effects are similar to those characterizing the entraining effects of melatonin on circadian patterns of locomotion and drinking

  13. Dynamic changes in genes related to glucose uptake and utilization during pig skeletal and cardiac muscle development.

    Science.gov (United States)

    Guo, Yanqin; Jin, Long; Wang, Fengjiao; He, Mengnan; Liu, Rui; Li, Mingzhou; Shuai, Surong

    2014-01-01

    Skeletal and cardiac muscle have important roles in glucose uptake and utilization. However, changes in expression of protein coding genes and miRNAs that participate in glucose metabolism during development are not fully understood. In this study, we investigated the expression of genes related to glucose metabolism during muscle development. We found an age-dependent increase in gene expression in cardiac muscle, with enrichment in heart development- and energy-related metabolic processes. A subset of genes that were up-regulated until 30 or 180 days postnatally, and then down-regulated in psoas major muscle was significantly enriched in mitochondrial oxidative-related processes, while genes that up-regulated in longissimus doris muscle was significantly enriched in glycolysis-related processes. Meanwhile, expression of energy-related microRNAs decreased with increasing age. In addition, we investigated the correlation between microRNAs and mRNAs in three muscle types across different stages of development and found many potential microRNA-mRNA pairs involved in regulating glucose metabolism.

  14. {sup 18}F-fluorodeoxyglucose and PET/CT for noninvasive study of exercise-induced glucose uptake in rat skeletal muscle and tendon

    Energy Technology Data Exchange (ETDEWEB)

    Skovgaard, Dorthe [University of Copenhagen, Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Bispebjerg Hospital, Institute of Sports Medicine, Copenhagen, NV (Denmark); Kjaer, Michael [Bispebjerg Hospital, Institute of Sports Medicine, Copenhagen, NV (Denmark); El-Ali, Henrik [University of Copenhagen, Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Kjaer, Andreas [University of Copenhagen, Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Rigshospitalet, Department Clinical Physiology, Nuclear Medicine and PET, Center of Diagnostic Investigations, Copenhagen (Denmark)

    2009-05-15

    To investigate exercise-related glucose uptake in rat muscle and tendon using PET/CT and to study possible explanatory changes in gene expression for the glucose transporters (GLUT1 and GLUT4). The sciatic nerve in eight Wistar rats was subjected to electrostimulation to cause unilateral isometric contractions of the calf muscle. {sup 18}F-Fluorodeoxyglucose was administered and a PET/CT scan of the hindlimbs was performed. SUVs were calculated in both Achilles tendons and the triceps surae muscles. To exclude a spill-over effect the tendons and muscles from an ex vivo group of eight rats were cut out and scanned separately (distance{>=}1 cm). Muscle contractions increased glucose uptake approximately sevenfold in muscles (p<0.001) and 36% in tendons (p<0.01). The ex vivo group confirmed the increase in glucose uptake in intact animals. GLUT1 and GLUT4 were expressed in both skeletal muscle and tendon, but no changes in mRNA levels could be detected. PET/CT can be used for studying glucose uptake in rat muscle and tendon in relation to muscle contractions; however, the increased uptake of glucose was not explained by changes in gene expression of GLUT1 and GLUT4. (orig.)

  15. Cyanidin-3-rutinoside increases glucose uptake by activating the PI3K/Akt pathway in 3T3-L1 adipocytes.

    Science.gov (United States)

    Choi, Kyung Ha; Lee, Hyun Ah; Park, Mi Hwa; Han, Ji-Sook

    2017-09-01

    In this study, the effect of cyanidin-3-rutinoside (C3R) on glucose uptake by 3T3-L1 adipocytes was studied. C3R significantly increased glucose uptake, which was associated with enhanced plasma membrane glucose transporter type 4 (PM-GLUT4) expression in 3T3-L1 adipocytes. The potentiating effect of C3R on glucose uptake and PM-GLUT4 expression was related to enhanced phosphorylation of insulin receptor substrate 1 (IRS-1) and Akt, as well as augmented activation of phosphatidylinositol-3-kinase (PI3K) in the insulin signaling pathway. C3R induced glucose uptake was inhibited only by the PI3K inhibitor, but not by an AMPK inhibitor in 3T3-L1 adipocytes. Therefore, C3R likely up-regulates glucose uptake and PM-GLUT4 expression in 3T3-L1 adipocytes by activating the PI3K/Akt pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. 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 Lajord

    2013-01-01

    tomography (PET)/computed tomography (CT). Ten patients with cirrhosis were studied during an acute episode of HE; nine were reexamined after recovery. Nine patients with cirrhosis with no history of HE served as controls. Mean CMRO(2) increased from 0.73 µmol oxygen/mL brain tissue/min during HE to 0......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...

  17. Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

    Directory of Open Access Journals (Sweden)

    Nagalakshmi Kamaraj

    2017-07-01

    Full Text Available Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide (poorly water soluble compound loaded polycaprolactone (nano-DDA was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy (SEM and dynamic light scattering (DLS studies. Fourier Transform InfraRed Spectroscopy (FTIR was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes. The nano-DDA displayed spherical shape with a smooth surface (252.898 nm diameter, zeta potential, encapsulation and loading efficiencies of −38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced (FTIR analysis. Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles (Rh123-PCL NPs revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude, our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

  18. DiabetterTM Reduces Post Meal Hyperglycemia Via Enhancement of Glucose Uptake Into Adipocytes and Muscles Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Mohd Hishamudin Mohd Jinal; Alqarni Bader Ayed; Shafii Khamis

    2014-01-01

    There are lots of herbal products for diabetes mellitus treatment available in local market. Most of these products are not standardized and lack of efficacy and safety data. DiaBetter TM is one of the herbal products that have been used for diabetes treatment. This study was carried out to determine the efficacy of DiaBetter TM in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. The results showed that DiaBetter TM significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetter TM significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54 fold (p<0.01) and 1.46 fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetter TM was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity of DiaBetter TM was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetter TM suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that the DiaBetter TM can be used as dietary adjunct for the management of type 2 diabetes mellitus which related to insulin resistance. (Author)

  19. Reliability of a progressive maximal cycle ergometer test to assess peak oxygen uptake in children with mild to moderate cerebral palsy

    NARCIS (Netherlands)

    Brehm, Merel-Anne; Balemans, Astrid C. J.; Becher, Jules G.; Dallmeijer, Annet J.

    2014-01-01

    Rehabilitation research in children with cerebral palsy (CP) is increasingly addressing cardiorespiratory fitness testing. However, evidence on the reliability of peak oxygen uptake (Vo2peak) measurements, considered the best indicator of aerobic fitness, is not available in this population. The

  20. Low whole-body insulin sensitivity in patients with ischaemic heart disease is associated with impaired myocardial glucose uptake predictive of poor outcome after revascularisation

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Carstensen, Steen; Hove, Jens D

    2002-01-01

    fluorodeoxyglucose and nitrogen-13 ammonia uptake in addition to quantified glucose uptake, blood flow and hyperaemic blood flow were assessed before CABG in 16 myocardial segments of the left ventricle. Major adverse cardiac events and LVEF were evaluated 7 months after CABG. Glucose uptake in normokinetic PET......-normal myocardium was found to be higher in patients with normal whole-body insulin sensitivity ( P segments displayed a pattern of reduced glucose uptake in normoperfused myocardium (PET-reverse mismatch) ( P ... was impaired in both patient groups. A major cardiac event after CABG could partly be predicted by the LV extent of normoperfused segments with PET-reverse mismatch. We conclude that low whole-body insulin sensitivity in patients with ischaemic heart disease and impaired LV function is associated with impaired...

  1. Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats.

    Science.gov (United States)

    Zielke, H Ronald; Zielke, Carol L; Baab, Peter J; Tildon, J Tyson

    2007-04-01

    Glucose is the primary carbon source to enter the adult brain for catabolic and anabolic reactions. Some studies suggest that astrocytes may metabolize glucose to lactate; the latter serving as a preferential substrate for neurons, especially during neuronal activation. The current study utilizes the aconitase inhibitor fluorocitrate to differentially inhibit oxidative metabolism in glial cells in vivo. Oxidative metabolism of 14C-lactate and 14C-glucose was monitored in vivo using microdialysis and quantitating 14CO2 in the microdialysis eluate following pulse labeling of the interstitial glucose or lactate pool. After establishing a baseline oxidation rate, fluorocitrate was added to the perfusate. Neither lactate nor glucose oxidation was affected by 5 micromol/L fluorocitrate. However, 20 and 100 micromol/L fluorocitrate reduced lactate oxidation by 55 +/- 20% and 68 +/- 12%, respectively (p fluorocitrate reduced 14C-glucose oxidation by 50 +/- 14% (p fluorocitrate decreased 14C-glucose oxidation by an additional 29% and 38%, respectively. These results indicate that astrocytes oxidize about 50% of the interstitial lactate and about 35% of the glucose. By subtraction, neurons metabolize a maximum of 50% of the interstitial lactate and 65% of the interstitial glucose.

  2. Acute exposure of primary rat soleus muscle to zilpaterol HCl (β2 adrenergic agonist), TNFα, or IL-6 in culture increases glucose oxidation rates independent of the impact on insulin signaling or glucose uptake.

    Science.gov (United States)

    Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Yates, Dustin T

    2017-08-01

    Recent studies show that adrenergic agonists and inflammatory cytokines can stimulate skeletal muscle glucose uptake, but it is unclear if glucose oxidation is similarly increased. Thus, the objective of this study was to determine the effects of ractopamine HCl (β1 agonist), zilpaterol HCl (β2 agonist), TNFα, and IL-6 on glucose uptake and oxidation rates in unstimulated and insulin-stimulated soleus muscle strips from adult Sprague-Dawley rats. Effects on phosphorylation of Akt (phospho-Akt), p38 MAPK (phospho-p38), and p44/42 MAPK (phospho-p44/42) was also determined. Incubation with insulin increased (Pglucose uptake by ∼47%, glucose oxidation by ∼32%, and phospho-Akt by ∼238%. Insulin also increased (Pglucose uptake but ∼32% greater (Pglucose oxidation than unstimulated muscle. Moreover, co-incubation with insulin+β2 agonist increased (Pglucose oxidation and phospho-Akt compared to insulin alone. Conversely, β1 agonist did not appear to affect basal or insulin-stimulated glucose metabolism, and neither β agonist affected phospho-p44/42. TNFα and IL-6 increased (Pglucose oxidation by ∼23% and ∼33%, respectively, in the absence of insulin. This coincided with increased (Pglucose oxidation rates that were similar to insulin alone, despite lower (Pglucose oxidation rates were not concomitant with greater glucose uptake. These results show that acute β2 adrenergic stimulation, but not β1 stimulation, directly increases fractional glucose oxidation in the absence of insulin and synergistically increases glucose oxidation when combined with insulin. The cytokines, TNFα and IL-6, likewise directly increased glucose oxidation in the absence of insulin, but were not additive in combination with insulin and in fact appeared to disrupt Akt-mediated insulin signaling. Rather, cytokines appear to be acting through MAPKs to elicit effects on glucose oxidation. Regardless, stimulation of glucose oxidation by these key stress factors did not rely upon

  3. The inability of phosphatidylinositol 3-kinase activation to stimulate GLUT4 translocation indicates additional signaling pathways are required for insulin-stimulated glucose uptake.

    Science.gov (United States)

    Isakoff, S J; Taha, C; Rose, E; Marcusohn, J; Klip, A; Skolnik, E Y

    1995-10-24

    Recent experimental evidence has focused attention to the role of two molecules, insulin receptor substrate 1 (IRS-1) and phosphatidylinositol 3-kinase (PI3-kinase), in linking the insulin receptor to glucose uptake; IRS-1 knockout mice are insulin resistant, and pharmacological inhibitors of PI3-kinase block insulin-stimulated glucose uptake. To investigate the role of PI3-kinase and IRS-1 in insulin-stimulated glucose uptake we examined whether stimulation of insulin-sensitive cells with platelet-derived growth factor (PDGF) or with interleukin 4 (IL-4) stimulates glucose uptake; the activated PDGF receptor (PDGFR) directly binds and activates PI3-kinase, whereas the IL-4 receptor (IL-4R) activates PI3-kinase via IRS-1 or the IRS-1-related molecule 4PS. We found that stimulation of 3T3-L1 adipocytes with PDGF resulted in tyrosine phosphorylation of the PDGFR and activation of PI3-kinase in these cells. To examine whether IL-4 stimulates glucose uptake, L6 myoblasts were engineered to overexpress GLUT4 as well as both chains of the IL-4R (L6/IL-4R/GLUT4); when these L6/IL-4R/GLUT4 myoblasts were stimulated with IL-4, IRS-1 became tyrosine phosphorylated and associated with PI3-kinase. Although PDGF and IL-4 can activate PI3-kinase in the respective cell lines, they do not possess insulin's ability to stimulate glucose uptake and GLUT4 translocation to the plasma membrane. These findings indicate that activation of PI3-kinase is not sufficient to stimulate GLUT4 translocation to the plasma membrane. We postulate that activation of a second signaling pathway by insulin, distinct from PI3-kinase, is necessary for the stimulation of glucose uptake in insulin-sensitive cells.

  4. The chemopreventive effect of the dietary compound kaempferol on the MCF-7 human breast cancer cell line is dependent on inhibition of glucose cellular uptake.

    Science.gov (United States)

    Azevedo, Cláudia; Correia-Branco, Ana; Araújo, João R; Guimarães, João T; Keating, Elisa; Martel, Fátima

    2015-01-01

    Our aim was to investigate the effect of several dietary polyphenols on glucose uptake by breast cancer cells. Uptake of (3)H-deoxy-D-glucose ((3)H-DG) by MCF-7 cells was time-dependent, saturable, and inhibited by cytochalasin B plus phloridzin. In the short-term (26 min), myricetin, chrysin, genistein, resveratrol, kaempferol, and xanthohumol (10-100 µM) inhibited (3)H-DG uptake. Kaempferol was found to be the most potent inhibitor of (3)H-DG uptake [IC50 of 4 µM (1.6-9.8)], behaving as a mixed-type inhibitor. In the long-term (24 h), kaempferol (30 µM) was also able to inhibit (3)H-DG uptake, associated with a 40% decrease in GLUT1 mRNA levels. Interestingly enough, kaempferol (100 µM) revealed antiproliferative (sulforhodamine B and (3)H-thymidine incorporation assays) and cytotoxic (extracellular lactate dehydrogenase activity determination) properties, which were mimicked by low extracellular (1 mM) glucose conditions and reversed by high extracellular (20 mM) glucose conditions. Finally, exposure of cells to kaempferol (30 µM) induced an increase in extracellular lactate levels over time (to 731 ± 32% of control after a 24 h exposure), due to inhibition of MCT1-mediated lactate cellular uptake. In conclusion, kaempferol potently inhibits glucose uptake by MCF-7 cells, apparently by decreasing GLUT1-mediated glucose uptake. The antiproliferative and cytotoxic effect of kaempferol in these cells appears to be dependent on this effect.

  5. Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers

    Science.gov (United States)

    Kay, Daniel B.; Karim, Helmet T.; Soehner, Adriane M.; Hasler, Brant P.; Wilckens, Kristine A.; James, Jeffrey A.; Aizenstein, Howard J.; Price, Julie C.; Rosario, Bedda L.; Kupfer, David J.; Germain, Anne; Hall, Martica H.; Franzen, Peter L.; Nofzinger, Eric A.; Buysse, Daniel J.

    2016-01-01

    Study Objectives: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). Methods: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21–60), sex, and race. We conducted [18F]fluoro-2-deoxy-d-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. Results: Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness. Citation: Kay DB, Karim HT, Soehner AM, Hasler BP, Wilckens KA, James JA, Aizenstein HJ, Price JC, Rosario BL, Kupfer DJ, Germain A, Hall MH, Franzen PL, Nofzinger EA, Buysse DJ. Sleep-wake differences in relative regional cerebral metabolic rate for glucose among patients with insomnia compared with good sleepers. SLEEP 2016;39(10):1779–1794. PMID:27568812

  6. ''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

  7. α-Glucosidase and pancreatic lipase inhibitory activities and glucose uptake stimulatory effect of phenolic compounds from Dendrobium formosum

    Directory of Open Access Journals (Sweden)

    Prachyaporn Inthongkaew

    Full Text Available ABSTRACT A methanol extract from the whole plant of Dendrobium formosum Roxb. ex Lindl., Orchidaceae, showed inhibitory potential against α-glucosidase and pancreatic lipase enzymes. Chromatographic separation of the extract resulted in the isolation of twelve phenolic compounds. The structures of these compounds were determined through analysis of NMR and HR-ESI-MS data. All of the isolates were evaluated for their α-glucosidase and pancreatic lipase inhibitory activities, as well as glucose uptake stimulatory effect. Among the isolates, 5-methoxy-7-hydroxy-9,10-dihydro-1,4-phenanthrenequinone (12 showed the highest α-glucosidase and pancreatic lipase inhibitory effects with an IC50 values of 126.88 ± 0.66 µM and 69.45 ± 10.14 µM, respectively. An enzyme kinetics study was conducted by the Lineweaver-Burk plot method. The kinetics studies revealed that compound 12 was a non-competitive inhibitor of α-glucosidase and pancreatic lipase enzymes. Moreover, lusianthridin at 1 and 10 µg/ml and moscatilin at 100 µg/ml showed glucose uptake stimulatory effect without toxicity on L6 myotubes. This study is the first report on the phytochemical constituents and anti-diabetic and anti-obesity activities of D. formosum.

  8. Design of a selective insulin receptor tyrosine kinase inhibitor and its effect on glucose uptake and metabolism in intact cells

    Energy Technology Data Exchange (ETDEWEB)

    Saperstein, R.; Vicario, P.P.; Strout, H.V.; Brady, E.; Slater, E.E.; Greenlee, W.J.; Onedyka, D.L.; Patchett, A.A.; Hangauer, D.G. (Merck Sharp and Dohme Research Labs., Rahway, NJ (USA))

    1989-06-27

    An inhibitor of the insulin receptor tyrosine kinase (IRTK), (hydroxy-2-napthalenylmethyl)phosphonic acid, was designed and synthesized and was shown to be an inhibitor of the biological effects of insulin in vitro. With a wheat germ purified human placental insulin receptor preparation, this compound inhibited the insulin-stimulated autophosphorylation of the 95-kDa {beta}-subunit of the insulin receptor. The ability of the kinase to phosphorylate an exogenous peptide substrate, angiotensin II, was also inhibited. Half-maximal inhibition of basal and insulin-stimulated human placental IRTK activity was found at concentrations of 150 and 100 {mu}M, respectively, with 2 mM angiotensin II as the peptide substrate. The inhibitor was found to be specific for tyrosine kinases over serine kinases and noncompetitive with ATP. The inhibitor was converted into various (acyloxy)methyl prodrugs in order to achieve permeability through cell membranes. These prodrugs inhibited insulin-stimulated autophosphorylation of the insulin receptor 95-kDa {beta}-subunit in intact CHO cells transfected with human insulin receptor. Inhibition of insulin-stimulated glucose oxidation in isolated rat adipocytes and 2-deoxyglucose uptake into CHO cells was observed with these prodrugs. The data provide additional evidence for the involvement of the insulin receptor tyrosine kinase in the regulation of glucose uptake and metabolism. These results and additional data reported herein suggest that this class of prodrugs and inhibitors will be useful for modulating the activity of a variety of tyrosine kinases.

  9. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.

    Science.gov (United States)

    Merrill, G F; Kurth, E J; Hardie, D G; Winder, W W

    1997-12-01

    5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 microU/ml insulin, and 10 mM glucose with or without AICAR (0.5-2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.

  10. Lactate and glutamate dynamics during prolonged stimulation of the rat barrel cortex suggest adaptation of cerebral glucose and oxygen metabolism.

    Science.gov (United States)

    Sonnay, Sarah; Duarte, João M N; Just, Nathalie

    2017-03-27

    A better understanding of BOLD responses stems from a better characterization of the brain's ability to metabolize glucose and oxygen. Non-invasive techniques such as functional magnetic resonance spectroscopy (fMRS) have thus been developed allowing for the reproducible assessment of metabolic changes during barrel cortex (S1BF) activations in rats. The present study aimed at further exploring the role of neurotransmitters on local and temporal changes in vascular and metabolic function in S1BF. fMRS and fMRI data were acquired sequentially in α-chloralose anesthetized rats during 32-min rest and trigeminal nerve stimulation periods. During stimulation, concentrations of lactate (Lac) and glutamate (Glu) increased in S1BF by 0.23±0.05 and 0.34±0.05μmol/g respectively in S1BF. Dynamic analysis of metabolite concentrations allowed estimating changes in cerebral metabolic rates of glucose (ΔCMR Glc ) and oxygen (ΔCMR O2 ). Findings confirmed a prevalence of oxidative metabolism during prolonged S1BF activation. Habituation led to a significant BOLD magnitude decline as a function of time while both total ΔCMR Glc and ΔCMR O2 remained constant revealing adaptation of glucose and oxygen metabolisms to support ongoing trigeminal nerve stimulation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. The effect of an acute nicotine infusion on the local cerebral glucose utilization of the awake rat.

    Science.gov (United States)

    Grünwald, F; Schröck, H; Kuschinsky, W

    1988-01-01

    The effect of acute infusion of nicotine on local cerebral glucose utilization (LCGU) was studied in discrete regions of the central nervous system of the rat by means of the quantitative autoradiographic (14C)2-deoxy-D-glucose method described by Sokoloff et al. Nicotine was administered in three dosages: 0.5 microgram/kg/min, 1.58 micrograms/kg/min, and 5 micrograms/kg/min. The resulting plasma concentrations of nicotine were 10/39/114 ng/ml plasma. During the experiment blood pressure, heart rate, body temperature, hematocrit, acid-base status, and plasma glucose concentration showed no or minor changes. Nicotine significantly increased LCGU in a dose-dependent manner in the following 9 of 45 examined structures: substantia nigra (compact part), superior colliculus (superficial grey layer), interpeduncular nucleus and cingulate cortex (P less than 0.01); lateral geniculate body, optic chiasm, anteroventral and anteromedial nucleus of thalamus and mamillary body (P less than 0.05). For most of these structures with increased LCGU, other investigators have reported a high regional receptor binding of nicotine (exception: mamillary body and optic chiasm). It is concluded that nicotine has distinct effects on the functional activity of localized brain areas.

  12. Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in Older Women Born from Normal Weight Mothers

    Directory of Open Access Journals (Sweden)

    Robert M. Badeau

    2017-02-01

    Full Text Available Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM or offspring of lean mothers (OLM. Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17 and elderly offspring from lean/normal weight mothers (OLM; n = 20 groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA was significantly lower in OOM (p = 0.015. DHA/FA associated significantly with skeletal muscle glucose uptake (GU (p = 0.031 and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value in the OLM group only (p = 0.050. Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.

  13. Enhancement of glucose uptake in muscular cell by soybean charged peptides isolated by electrodialysis with ultrafiltration membranes (EDUF): activation of the AMPK pathway.

    Science.gov (United States)

    Roblet, Cyril; Doyen, Alain; Amiot, Jean; Pilon, Geneviève; Marette, André; Bazinet, Laurent

    2014-03-15

    Soy peptides consumption has been associated with beneficial effects in type 2 diabetes patients. However, the peptide fractions responsible for these effects, and their mechanisms of action, have not been identified yet. In this study, we have isolated soybean peptides by electrodialysis with an ultrafiltration membrane (EDUF) at 50 V/100 kDa, and tested them for their capacity to improve glucose uptake in L6 muscle cells. We observed that these fractions were able to significantly enhance glucose uptake in the presence of insulin. The reported bioactivity would be due to the low molecular weight peptides (300-500 Da) recovered. Moreover, we observed that an enhancement of glucose uptake was correlated to the activation of the AMPK enzyme, well known for its capacity to increase glucose uptake in muscle cells. To our knowledge, this is the first time that bioactive peptides with glucose uptake activity have been isolated from a complex soy matrix, and that the implication of AMPK in it is demonstrated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Effects of Calorie Restriction and Fiber Type on Glucose Uptake and Abundance of Electron Transport Chain and Oxidative Phosphorylation Proteins in Single Fibers from Old Rats.

    Science.gov (United States)

    Wang, Haiyan; Arias, Edward B; Yu, Carmen S; Verkerke, Anthony R P; Cartee, Gregory D

    2017-11-09

    Calorie restriction (CR; reducing calorie intake by ~40% below ad libitum) can increase glucose uptake by insulin-stimulated muscle. Because skeletal muscle is comprised of multiple, heterogeneous fiber types, our primary aim was to determine the effects of CR (initiated at 14 weeks old) and fiber type on insulin-stimulated glucose uptake by single fibers of diverse fiber types in 23-26-month-old rats. Isolated epitrochlearis muscles from AL and CR rats were incubated with [3H]-2-deoxyglucose ± insulin. Glucose uptake and fiber type were determined for single fibers dissected from the muscles. We also determined CR-effects on abundance of several key metabolic proteins in single fibers. CR resulted in: (a) significantly (p glucose uptake by insulin-stimulated type I, IIA, IIB, IIBX, and IIX fibers; (b) significantly (p glucose uptake in each fiber type of rat skeletal muscle in the absence of upregulation of the abundance of hexokinase II or key mitochondrial ETC and OxPhos proteins. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Insulin and non-insulin mediated vasodilation and glucose uptake in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Olsen, David Benee; Reving, Danny

    2009-01-01

    AIMS: The objective was to re-examine endothelial function, insulin mediated vasodilation and glucose extraction in the forearm of patients with type 2 diabetes (T2DM) and matched control subjects (CON) to investigate whether blood flow impairments result from diabetes per se or from concurrent...... disease. METHODS: 18 subjects (10 with T2DM, 8 CON) had graded brachial artery infusions of endothelial dependent (acetylcholine: 15, 30, 60mug/min), endothelial independent (sodium nitroprusside: 1, 3, 10mug/min) and partially endothelial mediated (adenosine: 50, 150, 500mug/min) vasodilators...... forearm blood flow were similar in T2DM and CON. However, insulin mediated forearm blood flow responses and glucose extraction were lower in T2DM versus CON. CONCLUSION: The vasodilatory effect of insulin is impaired in T2DM although bulk flow capacity is maintained. Insulin mediated glucose extraction...

  16. Rapid vascular glucose uptake via enzyme-assisted subcutaneous infusion: enzyme-assisted subcutaneous infusion access study.

    Science.gov (United States)

    Soremekun, Olanrewaju A; Shear, Melissa L; Patel, Sagar; Kim, Gina J; Biddinger, Paul D; Parry, Blair A; Yialamas, Maria A; Thomas, Stephen H

    2009-11-01

    Enzyme-assisted subcutaneous infusion (EASI), with subcutaneous human recombinant hyaluronidase pretreatment, may offer an alternative to standard intravenous (IV) access. This study's objectives were to assess paramedic (Emergency Medical Technician-Paramedic [EMTP])-placed EASI access in volunteers to determine (1) feasibility of EMTP EASI access placement; (2) subject/EMTP ratings of placement ease, discomfort, and overall EASI vs IV preference; and (3) speed of intravascular uptake of EASI infusate. Twenty adults underwent 20-gauge IV placement by 4 EMTPs, receiving a 250-mL maximal-rate IV bolus of normal saline. Next, each subject received in the other arm a 20-gauge EASI access line (with 1-mL injection of 150 U of human recombinant hyaluronidase), through which was infused 250 mL D5NS (1 g glucose was labeled with stable tracer 13C). Blood draws enabled gas chromatography/mass spectrometry (GC/MS) assessment of 13C-glucose uptake. Intravenous access and EASI access were compared for time parameters and subject/EMTP ratings. Data were analyzed with median and interquartile range, Kruskal-Wallis testing, Fisher exact test, and regression (GC/MS data). Intravenous access and EASI access were successful in all 20 subjects. Compared with EASI access (all placed in EMTPs rated EASI easier to place than IV; pain ratings were similar for IV and EASI. The GC/MS showed intravascular uptake at all time points. Enzyme-assisted subcutaneous infusion is faster and easier to initiate than IV access; intravascular absorption of EASI-administered fluids begins within minutes.

  17. Regulation of myosin IIA and filamentous actin during insulin-stimulated glucose uptake in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Stall, Richard; Ramos, Joseph; Kent Fulcher, F.; Patel, Yashomati M., E-mail: ympatel@uncg.edu

    2014-03-10

    Insulin stimulated glucose uptake requires the colocalization of myosin IIA (MyoIIA) and the insulin-responsive glucose transporter 4 (GLUT4) at the plasma membrane for proper GLUT4 fusion. MyoIIA facilitates filamentous actin (F-actin) reorganization in various cell types. In adipocytes F-actin reorganization is required for insulin-stimulated glucose uptake. What is not known is whether MyoIIA interacts with F-actin to regulate insulin-induced GLUT4 fusion at the plasma membrane. To elucidate the relationship between MyoIIA and F-actin, we examined the colocalization of MyoIIA and F-actin at the plasma membrane upon insulin stimulation as well as the regulation of this interaction. Our findings demonstrated that MyoIIA and F-actin colocalized at the site of GLUT4 fusion with the plasma membrane upon insulin stimulation. Furthermore, inhibition of MyoII with blebbistatin impaired F-actin localization at the plasma membrane. Next we examined the regulatory role of calcium in MyoIIA-F-actin colocalization. Reduced calcium or calmodulin levels decreased colocalization of MyoIIA and F-actin at the plasma membrane. While calcium alone can translocate MyoIIA it did not stimulate F-actin accumulation at the plasma membrane. Taken together, we established that while MyoIIA activity is required for F-actin localization at the plasma membrane, it alone is insufficient to localize F-actin to the plasma membrane. - Highlights: • Insulin induces colocalization of MyoIIA and F-actin at the cortex in adipocytes. • MyoIIA is necessary but not sufficient to localize F-actin at the cell cortex. • MyoIIA-F-actin colocalization is regulated by calcium and calmodulin.

  18. Boehmeria nivea Stimulates Glucose Uptake by Activating Peroxisome Proliferator-Activated Receptor Gamma in C2C12 Cells and Improves Glucose Intolerance in Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Sung Hee Kim

    2013-01-01

    Full Text Available We examined the antidiabetic property of Boehmeria nivea (L. Gaud. Ethanolic extract of Boehmeria nivea (L. Gaud. (EBN increased the uptake of 2-[N-(nitrobenz-2-oxa-1,3-diazol-4-ylamino]-2-deoxy-d-glucose in C2C12 myotubes. To examine the mechanisms underlying EBN-mediated increase in glucose uptake, we examined the transcriptional activity and expression of peroxisome proliferator-activated receptor gamma (PPAR-γ, a pivotal target for glucose metabolism in C2C12 myotubes. We found that the EBN increased both the transcriptional activity and mRNA expression levels of PPAR-γ. In addition, we measured phosphorylation and expression levels of other targets of glucose metabolism, such as AMP-activated protein kinase (AMPK and protein kinase B (Akt/PKB. We found that EBN did not alter the phosphorylation or expression levels of these proteins in a time- or dose-dependent manner, which suggested that EBN stimulates glucose uptake through a PPAR-γ-dependent mechanism. Further, we investigated the antidiabetic property of EBN using mice fed a high-fat diet (HFD. Administration of 0.5% EBN reduced the HFD-induced increase in body weight, total cholesterol level, and fatty liver and improved the impaired fasting glucose level, blood insulin content, and glucose intolerance. These results suggest that EBN had an antidiabetic effect in cell culture and animal systems and may be useful for preventing diabetes.

  19. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    Science.gov (United States)

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

  20. effect of adrenaline on glucose uptake by the canine large bowel

    African Journals Online (AJOL)

    that the metabolism of the intestine in dogs, rabbits, cats guinea pig, sheep ... known whether this proximo-distal gradient in metabolic activities of the ... blood flow and sample collection for resting arterial and venous blood glucose were made. After the basal recording and blood sample collection, adrenaline,. 5ug/kg was ...

  1. Reducing the glucose uptake rate in Escherichia coli affects growth rate but not protein production.

    NARCIS (Netherlands)

    Picon, A.; Teixeira De Mattos, M.J.; Postma, P.W.

    2005-01-01

    Although glucose is an inexpensive substrate widely used as a carbon source in Escherichia coli recombinant fermentation technology, 10-30% of the carbon supply is wasted by excreting acetate. In addition to the loss of carbon source, the excretion of a weak acid may result in increased energetic

  2. Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling.

    Directory of Open Access Journals (Sweden)

    Yan Shen

    Full Text Available We previously demonstrated that cinnamon extract (CE ameliorates type 1 diabetes induced by streptozotocin in rats through the up-regulation of glucose transporter 4 (GLUT4 translocation in both muscle and adipose tissues. This present study was aimed at clarifying the detailed mechanism(s with which CE increases the glucose uptake in vivo and in cell culture systems using 3T3-L1 adipocytes and C2C12 myotubes in vitro. Specific inhibitors of key enzymes in insulin signaling and AMP-activated protein kinase (AMPK signaling pathways, as well as small interference RNA, were used to examine the role of these kinases in the CE-induced glucose uptake. The results showed that CE stimulated the phosphorylation of AMPK and acetyl-CoA carboxylase. An AMPK inhibitor and LKB1 siRNA blocked the CE-induced glucose uptake. We also found for the first time that insulin suppressed AMPK activation in the adipocyte. To investigate the effect of CE on type 2 diabetes in vivo, we further performed oral glucose tolerance tests and insulin tolerance tests in type 2 diabetes model rats administered with CE. The CE improved glucose tolerance in oral glucose tolerance tests, but not insulin sensitivity in insulin tolerance test. In summary, these results indicate that CE ameliorates type 2 diabetes by inducing GLUT4 translocation via the AMPK signaling pathway. We also found insulin antagonistically regulates the activation of AMPK.

  3. Thyroid hormone stimulated glucose uptake in human mononuclear blood cells from normal persons and from patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1989-01-01

    of stimulation of cells from control subjects and patients with NIDDM revealed an identical oxygen consumption, whereas the thyroid hormone-induced glucose uptake was significantly increased in cells from patients with NIDDM. T4 (5 mumol/l) stimulation in controls: 1.34 +/- 0.23 mmol.l-1 (mg DNA)-1.h-1, in NIDDM...... an increased thyroid hormone induced glucose uptake, indicating increased thyroid hormone sensitivity. This observation contrasts the well known insulin insensitivity, suggesting separate mechanisms for glucose uptake elicited by insulin and thyroid hormones....... by physiological and supraphysiological concentrations of T3 and T4 in a dose-dependent manner (50-5000 nmol/l), whereas rT3 and T2 had no stimulatory effect. The effect of T3 and T4 was independent of new protein synthesis in that it was not blocked by tunicamycin (1 mg/l) and tiothepa (75 mg/l). Examination...

  4. AMP-activated protein kinase (AMPK) {beta}1{beta}2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise

    DEFF Research Database (Denmark)

    O'Neill, Hayley M; Maarbjerg, Stine Just; Crane, Justin D

    2011-01-01

    of AMPK subunits in whole-body AMPK a2, ß2, and ¿3 null mice has made it difficult to determine the physiological importance of AMPK in regulating muscle metabolism, because these models have normal mitochondrial content, contraction-stimulated glucose uptake, and insulin sensitivity. In the current study......, we generated mice lacking both AMPK ß1 and ß2 isoforms in skeletal muscle (ß1ß2M-KO). ß1ß2M-KO mice are physically inactive and have a drastically impaired capacity for treadmill running that is associated with reductions in skeletal muscle mitochondrial content but not a fiber-type switch....... Interestingly, young ß1ß2M-KO mice fed a control chow diet are not obese or insulin resistant but do have impaired contraction-stimulated glucose uptake. These data demonstrate an obligatory role for skeletal muscle AMPK in maintaining mitochondrial capacity and contraction-stimulated glucose uptake, findings...

  5. Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles.

    Science.gov (United States)

    Jessen, Niels; Pold, Rasmus; Buhl, Esben S; Jensen, Lasse S; Schmitz, Ole; Lund, Sten

    2003-04-01

    Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression. Wistar rats were allocated into three groups: an exercise group trained on treadmill for 5 days, an AICAR group exposed to daily subcutaneous injections of AICAR, and a sedentary control group. AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions. Both exercised and AICAR-injected animals displayed a fiber-type-specific increase in glucose transport with the most marked increase in muscles with a high content of type IIb fibers. This increase was accompanied by a concomitant increase in GLUT-4 expression. Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner. In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.

  6. Akt and Rac1 signalling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance

    DEFF Research Database (Denmark)

    Sylow, Lykke; Kleinert, Maximilian; Pehmøller, Christian

    2014-01-01

    Skeletal muscle plays a major role in regulating whole body glucose metabolism. Akt and Rac1 are important regulators of insulin-stimulated glucose uptake in skeletal muscle. However the relative role of each pathway and how they interact is not understood. Here we delineate how Akt and Rac1...... pathways signal to increase glucose transport independently of each other and are simultaneously downregulated in insulin resistant muscle. Pharmacological inhibition of Rac1 and Akt signalling was used to determine the contribution of each pathway to insulin-stimulated glucose uptake in mouse muscles....... The actin filament-depolymerizing agent LatrunculinB was combined with pharmacological inhibition of Rac1 or Akt, to examine whether either pathway mediates its effect via the actin cytoskeleton. Akt and Rac1 signalling were investigated under each condition, as well as upon Akt2 knockout and in ob/ob mice...

  7. Rac1 signalling towards GLUT4/glucose uptake in skeletal muscle

    DEFF Research Database (Denmark)

    Chiu, Tim T; Jensen, Thomas Elbenhardt; Sylow, Lykke

    2011-01-01

    Small Rho family GTPases are important regulators of cellular traffic. Emerging evidence now implicates Rac1 and Rac-dependent actin reorganisation in insulin-induced recruitment of glucose transporter-4 (GLUT4) to the cell surface of muscle cells and mature skeletal muscle. This review summarises...... the current thinking on the regulation of Rac1 by insulin, the role of Rac-dependent cortical actin remodelling in GLUT4 traffic, and the impact of Rac1 towards insulin resistance in skeletal muscle....

  8. Insulin secretion and glucose uptake by isolated islets of the hamster

    International Nuclear Information System (INIS)

    Dunbar, J.C.; McLaughlin, W.J.; Walsh, M.F.J.; Foa, P.P.

    1976-01-01

    Isolated pancreatic islets of normal hamsters were perfused either in a closed or in a open system. When the buffer was recirculated and the endogenous insulin was allowed to accumulate, the islets secreted significantly less insulin than when the system was open and the endogenous insulin was washed away. The addition of monocomponent insulin or of proinsulin to the perfusion buffer significantly decreased insulin secretion. The inhibitory action of proinsulin was significantly greater than that of monocomponent insulin. C peptide had no effect. When pancreatic islets were incubated in a fixed volume of stationary buffer containing unlabeled glucose (1.0 mg or 3.0 mg/ml) and glucose-U- 14 C (1.0 μC/ml), the amount of insulin secreted and the 14 CO 2 produced by each islet decreased progressively as the number of islets in the sample increased. Under these conditions, the concentration of insulin required to inhibit insulin secretion increased with the concentration of glucose in the medium. Proinsulin did not alter the incorporation of leucine-4.5- 3 H into total extractable insulin (insulin + proinsulin). Thus, insulin and proinsulin appear to inhibit insulin release, but not insulin synthesis. (orig.) [de

  9. Glucose uptake during centrally induced stress is insulin independent and enhanced by adrenergic blockade.

    Science.gov (United States)

    Lekas, M C; Fisher, S J; El-Bahrani, B; van Delangeryt, M; Vranic, M; Shi, Z Q

    1999-08-01

    Glucose utilization increases markedly in the normal dog during stress induced by the intracerebroventricular (ICV) injection of carbachol. To determine the extent to which insulin, glucagon, and selective (alpha/beta)-adrenergic activation mediate the increment in glucose metabolic clearance rate (MCR) and glucose production (R(a)), we used five groups of normal mongrel dogs: 1) pancreatic clamp (PC; n = 7) with peripheral somatostatin (0.8 microg x kg(-1) x min(-1)) and intraportal replacement of insulin (1,482 +/- 84 pmol x kg(-1) x min(-1)) and glucagon (0.65 ng x kg(-1) x min(-1)) infusions; 2) PC plus combined alpha (phentolamine)- and beta (propranolol)-blockade (7 and 5 microg x kg(-1) x min(-1), respectively; alpha+beta; n = 5); 3) PC plus alpha-blockade (alpha; n = 6); 4) PC plus beta-blockade (beta; n = 5); and 5) a carbachol control group without PC (Con; n = 10). During ICV carbachol stress (0-120 min), catecholamines, ACTH, and cortisol increased in all groups. Baseline insulin and glucagon levels were maintained in all groups except Con, where glucagon rose 33%, and alpha, where insulin increased slightly but significantly. Stress increased (P glycogenolysis, and that R(a) is augmented by glucagon and alpha- and beta-catecholamine effects.

  10. β2-Adrenoceptors and non-β-adrenoceptors mediate effects of BRL37344 and clenbuterol on glucose uptake in soleus muscle: studies using knockout mice

    Science.gov (United States)

    Ngala, Robert A; O'Dowd, Jacqueline; Wang, Steven J; Stocker, Claire; Cawthorne, Michael A; Arch, Jonathan RS

    2009-01-01

    Background and purpose: In previous work, 10 pM BRL37344 and 10 pM clenbuterol stimulated glucose uptake in mouse soleus muscle. Ten nM BRL37344 also stimulated uptake but 100 nM clenbuterol inhibited uptake. Antagonist studies suggested that the opposite effects of 10 nM BRL37344 and 100 nM clenbuterol are mediated by the β2-adrenoceptor. BRL37344 and clenbuterol have been studied in muscles that lack β3-, β2- or all three β-adrenoceptors. Effects of β-adrenoceptor antagonists on responses to the agonists have been studied further using muscles from wild-type mice. Experimental approach: Soleus muscles of wild-type or β-adrenoceptor knockout mice were incubated with 2-deoxy[1-14C]-glucose, and β-adrenoceptor ligands. Formation of 2-deoxy[1-14C]-glucose-6-phosphate was measured. Key results: Concentration–response relationships were similar for BRL37344 and clenbuterol in normal muscle and muscle lacking β3-adrenoceptors. Ten pM BRL37344 and clenbuterol stimulated glucose uptake in muscle lacking β2-adrenoceptors or all three β-adrenoceptors, but 10 nM BRL37344 did not stimulate uptake in either case, and 100 nM clenbuterol stimulated, rather than inhibited, uptake in muscle lacking β2-adrenoceptors. One hundred nM clenbuterol also stimulated glucose uptake in normal muscle when β2-adrenoceptors were blocked with ICI118551, and this was not prevented by antagonism of β1- or β3-adrenoceptors. Conclusions and implications: Ten nM BRL37344 and 100 nM clenbuterol have opposite effects on glucose uptake but both effects are mediated by the β2-adrenoceptor – apparently an example of agonist-directed signalling. Ten pM BRL37344, 10 pM clenbuterol and 100 nM clenbuterol in the presence of ICI118551 stimulate glucose uptake via β-adrenoceptor-independent mechanisms, demonstrating unknown properties for the agonists. PMID:19912225

  11. The vanadyl chelate bis(acetylacetonato)oxovanadium(IV) increases the fractional uptake of 2-(fluorine-18)-2-deoxy-D-glucose by cultured human breast carcinoma cells

    OpenAIRE

    Makinen, Marvin W.; Bamba, Ravinder; Ikejimba, Linda; Wietholt, Christian; Chen, Chin-Tu; Conzen, Suzanne D

    2013-01-01

    Detection of breast cancer by positron emission tomography (PET) imaging with 2-(fluorine-18)-2-deoxy-D-glucose (FDG) as the tracer molecule is limited in part by both tumor dimension and metabolic activity. While some types of aggressive breast cancers are associated with a high capacity for FDG uptake, more indolent breast cancers are characterized by low FDG uptake. Moreover, detection of malignant lesions in most clinical settings requires tumor dimensions ≥ 10 mm. Development of a method...

  12. New findings on cerebral ammonia uptake in HE using functional (13)N-ammonia PET

    DEFF Research Database (Denmark)

    Sørensen, Michael; Keiding, Susanne

    2007-01-01

    ) analysed such data in patients with HE by a kinetic model accounting for transfer of (13)N-ammonia across the blood-brain barrier (BBB) and intracellular formation of (13)N-glutamine. Initial unidirectional (13)N-ammonia transfer across BBB was characterized by the permeability-surface area product PS...... metabolites was linearly correlated to arterial ammonia. In conclusion, basic brain ammonia kinetics was not changed significantly in patients with cirrhosis +/- HE compared to healthy controls. Blood ammonia seems to be the more important factor for increased brain ammonia uptake in HE. Udgivelsesdato: 2007......PET is a functional imaging technique suitable for studies of brain ammonia metabolism. Dynamic (13)N-ammonia PET yields time-courses of radioactivity concentrations in brain (PET camera) and blood (samples). Ahl et al. (Hepatology 40:73-79, 2004) and Keiding et al. (Hepatology 43:42-50, 2006...

  13. Peripheral metabolism of [18F]FDDNP and cerebral uptake of its labelled metabolites

    International Nuclear Information System (INIS)

    Luurtsema, Gert; Schuit, Robert C.; Takkenkamp, Kevin; Lubberink, Mark; Hendrikse, N. Harry; Windhorst, Albert D.; Molthoff, Carla F.M.; Tolboom, Nelleke; Berckel, Bart N.M. van; Lammertsma, Adriaan A.

    2008-01-01

    [ 18 F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [ 18 F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain. In humans, there was extensive metabolism of [ 18 F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar 18 F-labelled fragments, probably formed from N-dealkylation of [ 18 F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood-brain barrier and result in uniform brain uptake

  14. Regional cerebral incorporation of plasma [14C]palmitate, and cerebral glucose utilization, in water-deprived Long-Evans and Brattleboro rats

    International Nuclear Information System (INIS)

    Noronha, J.G.; Larson, D.M.; Rapoport, S.I.

    1989-01-01

    Regional rates of incorporation into brain of intravenously administered [ 14 C]palmitate and regional cerebral metabolic rates for glucose (rCMRglc) were measured in water-provided (WP) and water-deprived (WD) homozygous (DI) and heterozygous (HZ) Brattleboro rats, a mutant strain unable to synthesize vasopressin, and in the parent Long-Evans (LE) strain. Following 15 h or 4 days of water deprivation, rCMRglc was elevated threefold in the pituitary neural lobe of LE-WD and DI-WD as compared with LE-WP rats, and in the paraventricular nucleus of LE-WD, and the supraoptic nucleus of DI-WD rats. However, incorporation of [ 14 C]palmitate into these regions was not specifically altered. The results indicate that water deprivation for up to 4 days increases rCMRglc in some brain regions involved with vasopressin, but does not alter [ 14 C]palmitate incorporation into these regions. Incorporation of plasma [ 14 C]palmitate is independent of unlabeled plasma palmitate at brain regions which have an intact blood-brain barrier, but at nonbarrier regions falls according to saturation kinetics as cold plasma concentration rises, with a mean half-saturation constant (Km) equal to 0.136 mumol.ml-1

  15. Altered regional cerebral glucose metabolism in internet game overusers: a 18F-fluorodeoxyglucose positron emission tomography study.

    Science.gov (United States)

    Park, Hyun Soo; Kim, Sang Hee; Bang, Seong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Eun

    2010-03-01

    Internet game overuse is an emerging disorder and features diminished impulse control and poor reward-processing. In an attempt to understand the neurobiological bases of Internet game overuse, we investigated the differences in regional cerebral glucose metabolism at resting state between young individuals with Internet game overuse and those with normal use using 18F-fluorodeoxyglucose positron emission tomography study. Twenty right-handed male participants (9 normal users: 24.7+/-2.4 years of age, 11 overusers: 23.5+/-2.9 years of age) participated. A trait measure of impulsivity was also completed after scanning. Internet game overusers showed greater impulsiveness than the normal users and there was a positive correlation between the severity of Internet game overuse and impulsiveness. Imaging data showed that the overusers had increased glucose metabolism in the right middle orbitofrontal gyrus, left caudate nucleus, and right insula, and decreased metabolism in the bilateral postcentral gyrus, left precentral gyrus, and bilateral occipital regions compared to normal users. Internet game overuse may be associated with abnormal neurobiological mechanisms in the orbitofrontal cortex, striatum, and sensory regions, which are implicated in impulse control, reward processing, and somatic representation of previous experiences. Our results support the idea that Internet game overuse shares psychological and neural mechanisms with other types of impulse control disorders and substance/non-substance-related addiction.

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

    International Nuclear Information System (INIS)

    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 [ 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

  17. Intelligence and Changes in Regional Cerebral Glucose Metabolic Rate Following Learning.

    Science.gov (United States)

    Haier, Richard J.; And Others

    1992-01-01

    A study of eight normal right-handed men demonstrates widespread significant decreases in brain glucose metabolic rate (GMR) following learning a complex computer task, a computer game. Correlations between magnitude of GMR change and intelligence scores are also demonstrated. (SLD)

  18. Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

    Directory of Open Access Journals (Sweden)

    Sassi, A.,

    2017-10-01

    Full Text Available Trichosanthes cucumerina (Cucurbitaceae commonly known as Snake gourd or Labu Ular is considered the largest genre in the Cucurbitaceae family and is mainly found in the southeast areas of Asia. It has been used in Ayurvedic medicine as a treatment for certain diseases such as Diabetes mellitus, but these acclaims lack scientific-based evidence. In this study, water and ethanol extracts of three parts of Trichosanthes cucumerina namely; whole vegetable, peels, and seeds, were assessed for toxicity through a cell viability assay using 3T3-L1 pre-adipocytes model which revealed a maximum toleration concentration of 0.063 mg/mL. The extracts were further tested on adipocytes’ differentiation and positively showed a stimulation of lipid droplets formation during adipogenesis and significantly (p<0.001 increased glycerol release levels (75.34±3.69 μg/ml during adipolysis. The extracts also significantly (p<0.001 promoted the uptake of glucose into the cells (2636.22±91.33 Bq in an action similar to that of insulin. Similar results were observed during ELISA assay with a significant increase (p<0.001 in adiponectin concentrations (3593.1±225.25 ng/mL and a decrease in leptin concentrations (23870±5066.07 pg/mL. The present study results indicate a beneficial effect of Trichosanthes cucumerina extracts on adipogenesis, adipolysis and glucose uptake, in addition to a regulation of adiponectin and leptin concentrations in 3T3-L1 adipocytes which can be of clinical importance in energy regulation which is a key factor in treating diabetes, obesity, and metabolic syndrome.

  19. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of {sup 18}F-Fluorodeoxyglucose After Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, George D., E-mail: george.wilson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Oliver Wong, Ching Yee [Department of Diagnostic Radiology and Molecular Imaging Medicine, William Beaumont Hospital, Royal Oak, Michigan (United States); Yan, Di; Marples, Brian [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Huang, Jiayi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm{sup 3} they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: {sup 18}F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

  20. Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers.

    Science.gov (United States)

    Kay, Daniel B; Karim, Helmet T; Soehner, Adriane M; Hasler, Brant P; Wilckens, Kristine A; James, Jeffrey A; Aizenstein, Howard J; Price, Julie C; Rosario, Bedda L; Kupfer, David J; Germain, Anne; Hall, Martica H; Franzen, Peter L; Nofzinger, Eric A; Buysse, Daniel J

    2016-10-01

    The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMR glc ) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21-60), sex, and race. We conducted [ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMR glc . Significant group-by-state interactions in relative rCMR glc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at P corrected Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMR glc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness. © 2016 Associated Professional Sleep Societies, LLC.

  1. Measuring Steady-State Oxygen Uptake during the 6-Min Walk Test in Adults with Cerebral Palsy: Feasibility and Construct Validity

    Science.gov (United States)

    Maltais, Desiree B.; Robitaille, Nancy-Michelle; Dumas, Francine; Boucher, Normand; Richards, Carol L.

    2012-01-01

    This study evaluated the feasibility of measuring steady-state oxygen uptake (V[Combining Dot Above]O[subscript 2]) during the 6-min walk test (6MWT) in adults with cerebral palsy (CP) who walk without support and whether there is construct validity for net 6MWT V[Combining Dot Above]O[subscript 2] as a measure of their walking ability.…

  2. Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Haruka Amitani

    Full Text Available Hydrogen (H(2 acts as a therapeutic antioxidant. However, there are few reports on H(2 function in other capacities in diabetes mellitus (DM. Therefore, in this study, we investigated the role of H(2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2 promoted 2-[(14C]-deoxy-d-glucose (2-DG uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K, protein kinase C (PKC, and AMP-activated protein kinase (AMPK, although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p. and oral (p.o. administration. However, long-term p.o. administration of H(2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

  3. New findings on cerebral ammonia uptake in HE using functional (13)N-ammonia PET.

    Science.gov (United States)

    Sørensen, Michael; Keiding, Susanne

    2007-12-01

    PET is a functional imaging technique suitable for studies of brain ammonia metabolism. Dynamic (13)N-ammonia PET yields time-courses of radioactivity concentrations in brain (PET camera) and blood (samples). Ahl et al. (Hepatology 40:73-79, 2004) and Keiding et al. (Hepatology 43:42-50, 2006) analysed such data in patients with HE by a kinetic model accounting for transfer of (13)N-ammonia across the blood-brain barrier (BBB) and intracellular formation of (13)N-glutamine. Initial unidirectional (13)N-ammonia transfer across BBB was characterized by the permeability-surface area product PS(BBB) (ml blood min(-1) ml(-1) tissue). There was a tendency to lower PS(BBB) values in patients with cirrhosis and HE than in patients with cirrhosis without HE and healthy controls but the differences were not statistically significant. Keiding et al. (Hepatology 43:42-50, 2006) also calculated PS(met) (ml blood min(-1) ml(-1) tissue) as a measure of the combined transfer of (13)N-ammonia across BBB and subsequent intracellular metabolism of (13)N-ammonia; neither did this PS-value show significant difference between the groups of subjects. Net flux of ammonia from blood into intracellular metabolites was linearly correlated to arterial ammonia. In conclusion, basic brain ammonia kinetics was not changed significantly in patients with cirrhosis +/- HE compared to healthy controls. Blood ammonia seems to be the more important factor for increased brain ammonia uptake in HE.

  4. The effect of glucose stimulation on 45calcium uptake of rat pancreatic islets and their total calcium content as measured by a fluorometric micro-method

    International Nuclear Information System (INIS)

    Wolters, G.H.J.; Wiegman, J.B.; Konijnendijk, W.

    1982-01-01

    Glucose-stimulated 45 calcium uptake and total calcium content of rat pancreatic islets has been studied, using a new fluorometric micro-method to estimate total calcium. Extracellular calcium was separated from incubated tissue by a rapid micro-filtration procedure. Islets incubated up to 60 min with calcium chloride 2.5 mmol/l and glucose 2.5 mmol/l maintained the same calcium content (670 +- 7.5 pmol/μg DNA). When the glucose concentration was raised to 15 mmol/l no change in the total calcium content could be detected. On incubation with glucose 2.5 mmol/l in the absence of calcium, the calcium content decreased to 488 +- 27 pmol/μg DNA. On incubation with 45 calcium chloride 2.5 mmol/l for 5 or 30 min at 2.5 mmol/l glucose, islets exchanged 21 +- 2 and 28 +- 1% of their total calcium content and, at 15 mmol/l glucose, 30 +- 3 and 45 +- 2%, respectively. Thus, islet calcium has a high turn-over rate. Glucose stimulation results in an increase of the calcium uptake without enhancing the total calcium content and hence must increase the calcium-exchangeable pool. (orig.)

  5. α-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation in 3T3-L1 Cells via PPARγ, GLUT4, and Leptin Expressions

    Directory of Open Access Journals (Sweden)

    Muhammad Taher

    2015-01-01

    Full Text Available Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[3H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P<0.05 with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.

  6. Effects of 12-wk eccentric calf muscle training on muscle-tendon glucose uptake and SEMG in patients with chronic Achilles tendon pain

    DEFF Research Database (Denmark)

    Masood, Tahir; Kalliokoski, Kari; Magnusson, S Peter

    2014-01-01

    High-load eccentric exercises have been a key component in the conservative management of chronic Achilles tendinopathy. This study investigated the effects of a 12-wk progressive, home-based eccentric rehabilitation program on ankle plantar flexors' glucose uptake (GU) and myoelectric activity a...

  7. Calorie restriction enhances insulin-stimulated glucose uptake and Akt phosphorylation in both fast-twitch and slow-twitch skeletal muscle of 24-month-old rats.

    Science.gov (United States)

    Sequea, Donel A; Sharma, Naveen; Arias, Edward B; Cartee, Gregory D

    2012-12-01

    Calorie restriction (CR) induces enhanced insulin-stimulated glucose uptake in fast-twitch (type II) muscle from old rats, but the effect of CR on slow-twitch (type I) muscle from old rats is unknown. The purpose of this study was to assess insulin-stimulated glucose uptake and phosphorylation of key insulin signaling proteins in isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from 24-month-old ad libitum fed and CR (consuming 65% of ad libitum, intake) rats. Muscles were incubated with and without 1.2 nM insulin. CR versus ad libitum rats had greater insulin-stimulated glucose uptake and Akt phosphorylation (pAkt) on T308 and S473 for both muscles incubated with insulin. GLUT4 protein abundance and phosphorylation of the insulin receptor (Y1162/1163) and AS160 (T642) were unaltered by CR in both muscles. These results implicate enhanced pAkt as a potential mechanism for the CR-induced increase in insulin-stimulated glucose uptake by the fast-twitch epitrochlearis and slow-twitch soleus of old rats.

  8. Insulin-Induced Microvascular Recruitment in Skin and Muscle are Related and Both are Associated with Whole-Body Glucose Uptake

    NARCIS (Netherlands)

    Meijer, R.I.; de Boer, M.P.; Groen, M.R.; Eringa, E.C.; Rattigan, S.; Barrett, E.J.; Smulders, Y.M.; Serné, E.H.

    2012-01-01

    Objective: Insulin-induced capillary recruitment is considered a determinant of insulin-mediated glucose uptake. Insulin action on the microvasculature has been assessed in skin; however, there is concern as to whether the vascular responses observed in skin reflect those in the muscle. We

  9. Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging

    DEFF Research Database (Denmark)

    Reichkendler, M. H.; Auerbach, P.; Rosenkilde, M.

    2013-01-01

    Physical exercise increases peripheral insulin sensitivity, but regional differences are poorly elucidated in humans. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions, us...

  10. Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

    DEFF Research Database (Denmark)

    Frøsig, Christian; Roepstorff, Carsten; Brandt, Nina

    2009-01-01

    compared with a high-carbohydrate diet [65 energy-% (CHO)]. After 4 days of isocaloric diet on two occasions (Fat/CHO), 12 male subjects performed 1 h of one-legged knee extensor exercise (approximately 80% peak workload). Four hours after exercise, insulin-stimulated glucose uptake was determined in both...

  11. Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway.

    Science.gov (United States)

    Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

    2016-12-09

    Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na⁺-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C ) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

  12. Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Kang-Hyun Leem

    2016-12-01

    Full Text Available Opuntia ficus-indica var. saboten (OFS has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na+-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C and p38 MAPK (SB203580 abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4 translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

  13. Hydro-ethanolic extract of cashew tree (Anacardium occidentale) nut and its principal compound, anacardic acid, stimulate glucose uptake in C2C12 muscle cells.

    Science.gov (United States)

    Tedong, Leonard; Madiraju, Padma; Martineau, Louis C; Vallerand, Diane; Arnason, John T; Desire, Dzeufiet D P; Lavoie, Louis; Kamtchouing, Pierre; Haddad, Pierre S

    2010-12-01

    Products of cashew tree (Anacardium occidentale) are used in traditional medicine for various ailments, including diabetes. The anti-diabetic properties of cashew plant parts were studied using differentiated C2C12 myoblasts (myotubes) and rat liver mitochondria. Hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (AA), stimulated glucose transport into C2C12 myotubes in a concentration-dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 μg/mL CSE. CSE and AA caused activation of adenosine monophosphate-activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate-stimulated respiration in rat liver mitochondria. Activation of adenosine monophosphate-activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti-diabetic nutraceutical. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Transient Silencing of a Type IV P-Type ATPase, Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    S. E. Hurst

    2012-01-01

    Full Text Available Atp10c is a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C, Atp10c expression was altered in vitro in C2C12 skeletal muscle myotubes by transient transfection with an Atp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs, p38, and p44/42. Additionally, glucose transporter-1 (GLUT1 was significantly upregulated; no changes in glucose transporter-4 (GLUT4 expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate that Atp10c regulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.

  15. Evidence for compromised metabolic function and limited glucose uptake in spermatozoa from the teratospermic domestic cat (Felis catus) and cheetah (Acinonyx jubatus).

    Science.gov (United States)

    Terrell, Kimberly A; Wildt, David E; Anthony, Nicola M; Bavister, Barry D; Leibo, Stanley P; Penfold, Linda M; Marker, Laurie L; Crosier, Adrienne E

    2010-11-01

    Cheetahs and certain other felids consistently ejaculate high proportions (≥ 60%) of malformed spermatozoa, a condition known as teratospermia, which is prevalent in humans. Even seemingly normal spermatozoa from domestic cat teratospermic ejaculates have reduced fertilizing capacity. To understand the role of sperm metabolism in this phenomenon, we conducted a comparative study in the normospermic domestic cat versus the teratospermic cat and cheetah with the general hypothesis that sperm metabolic function is impaired in males producing predominantly pleiomorphic spermatozoa. Washed ejaculates were incubated in chemically defined medium containing glucose and pyruvate. Uptake of glucose and pyruvate and production of lactate were assessed using enzyme-linked fluorescence assays. Spermatozoa from domestic cats and cheetahs exhibited similar metabolic profiles, with minimal glucose metabolism and approximately equimolar rates of pyruvate uptake and lactate production. Compared to normospermic counterparts, pyruvate and lactate metabolism were reduced in teratospermic cat and cheetah ejaculates, even when controlling for sperm motility. Rates of pyruvate and lactate (but not glucose) metabolism were correlated positively with sperm motility, acrosomal integrity, and normal morphology. Collectively, our findings reveal that pyruvate uptake and lactate production are reliable, quantitative indicators of sperm quality in these two felid species and that metabolic function is impaired in teratospermic ejaculates. Furthermore, patterns of substrate utilization are conserved between these species, including the unexpected lack of exogenous glucose metabolism. Because glycolysis is required to support sperm motility and capacitation in certain other mammals (including dogs), the activity of this pathway in felid spermatozoa is a target for future investigation.

  16. The relationship between the cerebral blood flow, oxygen consumption and glucose metabolism in primary degenerative dementia

    International Nuclear Information System (INIS)

    Kuwabara, Yasuo; Ichiya, Yuichi; Ichimiya, Atsushi; Sasaki, Masayuki; Akashi, Yuko; Yoshida, Tsuyoshi; Fukumura, Toshimitsu; Masada, Kouji

    1995-01-01

    The CBF, CMRO 2 and CMRGlu were measured in patients with primary degenerative dementia including 5 patients with dementia of Alzheimer's type and 4 patients with Pick's disease, and then the correlation between the cerebral blood flow and energy metabolism was evaluated. The control subjects consisted of 5 age-matched normal volunteers. The CBF, CMRO 2 and CMRGlu decreased in the bilateral frontal, temporal and parietal regions in the patients with Alzheimer's dementia, while they decreased in the bilateral frontal and temporal regions in the patients with Pick's disease. Both the CBF and CMRO 2 were closely correlated with each other. However, the CMRGlu was more severely impaired than the CBF or CMRO 2 in both pathological conditions. These results suggested that CMRGlu began to decrease before the reduction of the aerobic metabolism and thus measuring the CMRGlu is considered to be the most sensitive method for detecting abnormal regions in primary degenerative dementia. (author)

  17. 18F-fluorodeoxyglucose and PET/CT for noninvasive study of exercise-induced glucose uptake in rat skeletal muscle and tendon

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Kjaer, Michael; El-Ali, Henrik

    2009-01-01

    unilateral isometric contractions of the calf muscle. (18)F-Fluorodeoxyglucose was administered and a PET/CT scan of the hindlimbs was performed. SUVs were calculated in both Achilles tendons and the triceps surae muscles. To exclude a spill-over effect the tendons and muscles from an ex vivo group of eight......PURPOSE: To investigate exercise-related glucose uptake in rat muscle and tendon using PET/CT and to study possible explanatory changes in gene expression for the glucose transporters (GLUT1 and GLUT4). METHODS: The sciatic nerve in eight Wistar rats was subjected to electrostimulation to cause...... rats were cut out and scanned separately (distance>or=1 cm). RESULTS: Muscle contractions increased glucose uptake approximately sevenfold in muscles (p

  18. Mapping of change in cerebral glucose utilization using fluorine-18 fluorodeoxyglucose double injection and the constrained weighted-integration method

    Energy Technology Data Exchange (ETDEWEB)

    Murase, K. [McGill Univ., Montreal, Quebec (Canada)]|[Ehime University School of Medicine (Japan). Dept. of Radiology; Kuwabara, Hiroto [West Virginia Univ., Morgantown, WV (United States). Center for Advanced Imaging; Yasuhara, Yoshifumi; Evans, A.C. [McGill Univ., Montreal, Quebec (Canada); Gjedde, A. [Aarhus General Hospital (Denmark). PET Center

    1996-12-01

    The authors developed a method for mapping the change in cerebral glucose utilization at two different physiological states using [{sup 18}F]fluorodeoxyglucose (FDG) double injection and the constrained weighted-integration method. They studied young normal subjects without (baseline-baseline group, n = 5) and with (baseline-stimulation group, n = 5) vibrotactile stimulation of the fingertips of the right hand. Dynamic scans were performed using positron emission tomography (PET) following an initial dose (the first session, 0--30 min) and an additional dose (the second session, 30--60 min). The parametric images of the net clearance of FDG from blood to brain (K*), unidirectional blood-to-brain clearance (K*{sub 1}) and cerebral metabolic rate of glucose (CMR{sub glc}) of the two sessions were generated. The averaged subtraction (second minus first session) and t-statistic images were generated, which were rendered into Talairach`s sterotaxic coordinates and merged with the averaged magnetic resonance imaging (MRI) image. In the baseline-baseline group, regional K*, K*{sub 1}, and CMR{sub glc} in the first and second sessions were strongly correlated (r{sup 2} = 0.953, 0.935, and 0.951, respectively, n = 340). In the baseline-stimulation group, significant increases in these estimates were obtained in the contralateral primary somatosensory cortex (SI) (from 3.43 {+-} 0.78 to 4.02 {+-} 1.01 ml/100 g/min for K*, 7.85 {+-} 1.88 to 9.09 {+-} 1.71 ml/100 g/min for K*{sub 1}, and 28.0 {+-} 5.9 to 32.3 {+-} 5.5 {micro}mol/100 g/min for CMR{sub glc}), while there were no significant changes in the ipsilateral SI (from 3.45 {+-} 0.84 to 3.39 {+-} 0.72 ml/100 g/min for K*, 8.17 {+-} 2.33 to 8.37 {+-} 1.75 ml/100 g/min for K*{sub 1}, and 29.5 {+-} 8.1 to 29.1 {+-} 8.2 {micro}mol/100 g/min for CMR{sub glc}). Significant increases in K* and CMR{sub glc} in the contralateral SI were clearly demonstrated in the t-statistic image.

  19. Voxel-based analysis of cerebral glucose metabolism in AD and non-AD degenerative dementia using statistical parametric mapping

    International Nuclear Information System (INIS)

    Li Zugui; Gao Shuo; Zhang Benshu; Ma Aijun; Cai Li; Li Dacheng; Li Yansheng; Liu Lei

    2008-01-01

    Objective: It is know that Alzheimer's disease (AD) and non-AD degenerative dementia have some clinical features in common. The aim of this study was to investigate the specific patterns of regional, cerebral glucose metabolism of AD and non-AD degenerative dementia patients, using a voxel-based 18 F-fluorodeoxyglucose (FDG) PET study. Methods: Twenty-three AD patients and 24 non-AD degenerative dementia patients including 9 Parkinson's disease with dementia(PDD), 7 frontal-temporal dementia (FTD), 8 dementia of Lewy bodies (DLB) patients, and 40 normal controls (NC)were included in the study. To evaluate the relative cerebral metabolic rate of glucose (rCMRglc), 18 F-FDG PET imaging was performed in all subjects. Subsequently, statistical comparison of PET data with NC was performed using statistical parametric mapping (SPM). Results: The AD-associated FDG imaging pattern typically presented as focal cortical hypometabolism in bilateral parietotemporal association cortes and(or) frontal lobe and the posterior cingulate gyms. As compared with the comparative NC, FTD group demonstrated significant regional reductions in rCMRglc in bilateral frontal, parietal lobes, the cingulate gyri, insulae, left precuneus, and the subcortical structures (including right putamen, right medial dorsal nucleus and ventral anterior nucleus). The PDD group showed regional reductions in rCMRglc in bilateral frontal cortexes, parietotemporal association cortexes, and the subcortical structures (including left caudate, right putamen, the dorsomedial thalamus, lateral posterior nucleus, and pulvinar). By the voxel-by-voxel comparison between the DLB group and NC group, regional reductions in rCMRglc included bilateral occipital cortexes, precuneuses, frontal and parietal lobes, left anterior cingulate gyms, right superior temporal cortex, and the subcortical structures including putamen, caudate, lateral posterior nucleus, and pulvinar. Conclusions: The rCMRglc was found to be different

  20. Reduced connexin43 expression correlates with c-Src activation, proliferation, and glucose uptake in reactive astrocytes after an excitotoxic insult.

    Science.gov (United States)

    Gangoso, Ester; Ezan, Pascal; Valle-Casuso, José Carlos; Herrero-González, Sandra; Koulakoff, Annette; Medina, Jose M; Giaume, Christian; Tabernero, Arantxa

    2012-12-01

    In diverse brain pathologies, astrocytes become reactive and undergo profound phenotypic changes. Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes, is one of the proteins modified in reactive astrocytes. Downregulation of Cx43 in cultured astrocytes activates c-Src, promotes proliferation, and increases the rate of glucose uptake; however, so far there have been no studies examining whether this cascade of events takes place in reactive astrocytes. In this work, we analyzed this pathway after a cortical lesion induced by a kainic acid injection. As previously described, astrocytes reacted to the lesion with an increase in glial fibrillary acidic protein and a decrease in Cx43 expression. Some of these reactive astrocytes proliferated, as estimated by bromodeoxyuridine incorporation and cyclins D1 and D3 upregulation. In addition, the expression of the glucose transporter GLUT-3 and the enzyme responsible for glucose phosphorylation, Type II hexokinase (Hx-2), were induced in reactive astrocytes, suggesting an increased glucose uptake. Previous in vitro studies reported that c-Src is the link between Cx43 and glucose uptake and proliferation in astrocytes. Here, we found that c-Src activity increased in the lesioned area. c-Src activation and Cx43 downregulation preceded the peak of Hx-2 and cyclin D3 expression, suggesting that c-Src could mediate the effect of Cx43 on glucose uptake and proliferation in reactive astrocytes after an excitotoxic insult. Interestingly, we identify c-Src, GLUT-3, and Hx-2 in the signaling mechanisms involved in the reaction of astroglia to injury. Altogether these data contribute to identify new therapeutical targets to enhance astrocyte neuroprotective activities. Copyright © 2012 Wiley Periodicals, Inc.

  1. Regional cerebral glucose metabolism is normal in young adults with Down syndrome

    International Nuclear Information System (INIS)

    Schapiro, M.B.; Grady, C.L.; Kumar, A.; Herscovitch, P.; Haxby, J.V.; Moore, A.M.; White, B.; Friedland, R.P.; Rapoport, S.I.

    1990-01-01

    Regional CMRglc (rCMRglc) values were measured with [ 18 F]2-fluoro-2-deoxy-D-glucose ( 18 FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur

  2. Exercise and heat stress: cerebral challenges and consequences

    DEFF Research Database (Denmark)

    Nybo, Lars

    2007-01-01

    This review deals with new aspects of exercise in the heat as a challenge that not only influences the locomotive and cardiovascular systems, but also affects the brain. Activation of the brain during such exercise is manifested in the lowering of the cerebral glucose to oxygen uptake ratio, the ...

  3. 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.)

  4. 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

    2017-01-01

    by mass spectrometry. The ATP synthesis rate of isolated whole-brain mitochondria was assessed by an on-line luciferin-luciferase assay. Significantly increased (13)C labeling of intracellular lactate and alanine and decreased tricarboxylic acid (TCA) cycle activity were observed from cerebral cortical...... rate tended to be decreased in isolated whole-brain mitochondria of APPswe/PSEN1dE9 mice. Thus, several cerebral metabolic changes are evident in the APPswe/PSEN1dE9 mouse prior to amyloid plaque deposition, including altered glucose metabolism, hampered glutamine processing and mitochondrial......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...

  5. Effect of magnesium treatment and glucose levels on delayed cerebral ischemia in patients with subarachnoid hemorrhage : A substudy of the Magnesium in Aneurysmal Subarachnoid Haemorrhage trial (MASH-II)

    NARCIS (Netherlands)

    Leijenaar, Jolien F.; Dorhout Mees, Sanne M.; Algra, Ale; van den Bergh, Walter M.; Rinkel, Gabriel J. E.

    2015-01-01

    Background: Magnesium treatment did not improve outcome in patients with aneurysmal subarachnoid haemorrhage in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. We hypothesized that high glucose levels may have offset a potential beneficial effect to prevent delayed cerebral ischemia.

  6. Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models. Evaluation of insulin and β3-adrenergic receptor agonist effects by 18F-FDG

    International Nuclear Information System (INIS)

    Ishino, Seigo; Sugita, Taku; Kondo, Yusuke

    2017-01-01

    One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals. A radiotracer for glucose, 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316, 243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. 18 F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography. In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin

  7. The E. coli pET expression system revisited-mechanistic correlation between glucose and lactose uptake.

    Science.gov (United States)

    Wurm, David Johannes; Veiter, Lukas; Ulonska, Sophia; Eggenreich, Britta; Herwig, Christoph; Spadiut, Oliver

    2016-10-01

    Therapeutic monoclonal antibodies are mainly produced in mammalian cells to date. However, unglycosylated antibody fragments can also be produced in the bacterium Escherichia coli which brings several advantages, like growth on cheap media and high productivity. One of the most popular E. coli strains for recombinant protein production is E. coli BL21(DE3) which is usually used in combination with the pET expression system. However, it is well known that induction by isopropyl β-D-1-thiogalactopyranoside (IPTG) stresses the cells and can lead to the formation of insoluble inclusion bodies. In this study, we revisited the pET expression system for the production of a novel antibody single-chain variable fragment (scFv) with the goal of maximizing the amount of soluble product. Thus, we (1) investigated whether lactose favors the recombinant production of soluble scFv compared to IPTG, (2) investigated whether the formation of soluble product can be influenced by the specific glucose uptake rate (q s,glu) during lactose induction, and (3) determined the mechanistic correlation between the specific lactose uptake rate (q s,lac) and q s,glu. We found that lactose induction gave a much greater amount of soluble scFv compared to IPTG, even when the growth rate was increased. Furthermore, we showed that the production of soluble protein could be tuned by varying q s,glu during lactose induction. Finally, we established a simple model describing the mechanistic correlation between q s,lac and q s,glu allowing tailored feeding and prevention of sugar accumulation. We believe that this mechanistic model might serve as platform knowledge for E. coli.

  8. Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake.

    Science.gov (United States)

    Motiani, Kumail K; Savolainen, Anna M; Eskelinen, Jari-Joonas; Toivanen, Jussi; Ishizu, Tamiko; Yli-Karjanmaa, Minna; Virtanen, Kirsi A; Parkkola, Riitta; Kapanen, Jukka; Grönroos, Tove J; Haaparanta-Solin, Merja; Solin, Olof; Savisto, Nina; Ahotupa, Markku; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K; Hannukainen, Jarna C

    2017-05-01

    Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [ 18 F]FDG and [ 18 F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity ( P = 0.001) and whole body insulin sensitivity ( P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) ( P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = -4%; MICT = 13%) ( P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = -6%; MICT = -48%) ( P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = -38%) ( P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism. NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques

  9. Noninvasive quantification of cerebral metabolic rate for glucose in rats using (18)F-FDG PET and standard input function.

    Science.gov (United States)

    Hori, Yuki; Ihara, Naoki; Teramoto, Noboru; Kunimi, Masako; Honda, Manabu; Kato, Koichi; Hanakawa, Takashi

    2015-10-01

    Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed (18)F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIF(NS)) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF(1S)). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIF(NS)-, and EIF(1S)-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIF(NS) was highly correlated with those derived from AIF and EIF(1S). Preliminary comparison between AIF and EIF(NS) in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIF(NS) method might serve as a noninvasive substitute for individual AIF measurement.

  10. Effect of thyroxine on cellular oxygen-consumption and glucose uptake: evidence of an effect of total T4 and not "free T4"

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L E

    1990-01-01

    in human mononuclear blood cells. Cells were incubated in protein free medium and in human serum totally depleted of thyroid hormones by resin treatment and fixed amounts of T4 (total T4 = 0-50-100-5000 nmol/l; free T4 = 0-5-11-5600 pmol/l) were added. Thyroxine stimulated glucose uptake and oxygen......Recent studies of cellular T4 and T3 uptake have indicated active transport of the hormones into the cell rather than passive diffusion of the non-protein bound fraction. In order to study the significance of the extracellular environment, oxygen consumption and glucose uptake were examined......K-ATPase by addition of ouabain (9-72 mg/l) did not inhibit T4 stimulation, thus indicating that the ouabain sensitive NaK-ATPase is not a major component of the processes which initiate the intracellular effects of T4. Therefore the stimulation of uptake of oxygen and glucose in human mononuclear blood cells seems...

  11. 3-O-Acyl-epicatechins Increase Glucose Uptake Activity and GLUT4 Translocation through Activation of PI3K Signaling in Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Manabu Ueda-Wakagi

    2015-07-01

    Full Text Available Tea catechins promote glucose uptake in skeletal muscle cells. In this study, we investigated whether the addition of an acyl group to the C-3 position of catechins to generate 3-O-acyl-catechins promoted glucose uptake in L6 myotubes. 3-O-Myristoyl-(−-epicatechin (EC-C14 and 3-O-palmitoyl-(−-epicatechin (EC-C16 promoted glucose uptake and translocation of glucose transporter (GLUT 4 in the cells. The effect of 3-O-acyl-(−-epicatechins was stronger than that of (−-epicatechin (EC, whereas neither 3-O-myristoyl-(+-catechin (C-C14 nor 3-O-palmitoyl-(+catechin (C-C16 promoted glucose uptake or GLUT4 translocation as well as (+-catechin (C. We further investigated an affinity of catechins and 3-O-acyl-catechins to the lipid bilayer membrane by using surface plasma resonance analysis. Maximum binding amounts of EC-C16 and C-C16 to the lipid bilayer clearly increased compared with that of (−-EC and (+-C, respectively. We also examined the mechanism of GLUT4 translocation and found EC-C14 and EC-C16 induced the phosphorylation of PI3K, but did not affect phosphorylation of Akt or IR. In conclusion, the addition of an acyl group to the C-3 position of (−-EC increases its affinity for the lipid bilayer membrane and promotes GLUT4 translocation through PI3K-dependent pathways in L6 myotubes.

  12. Structural Elucidation of a Novel Polysaccharide from Pseudostellaria heterophylla and Stimulating Glucose Uptake in Cells and Distributing in Rats by Oral.

    Science.gov (United States)

    Chen, Jinlong; Pang, Wensheng; Shi, Wentao; Yang, Bin; Kan, Yongjun; He, Zhaodong; Hu, Juan

    2016-09-14

    The semi-refined polysaccharide of Pseudostellaria heterophylla is a complex polysaccharide that exhibits significantly hypoglycemic activities. A novel homogeneous polysaccharide, named as H-1-2, was isolated from the semi-refined polysaccharide. The mean molecular weight of H-1-2 was 1.4 × 10⁴ Da and it was only composed of d-glucose monosaccharide. Structure elucidation indicated that H-1-2 contains pyranride, and has the characteristics of the α-iso-head configuration, a non-reducing end (T-), 4-, 1,6-, and 1,4,6-connection, in all four ways to connect glucose. H-1-2 was a type of glucan, where chemical combination exists in the main chain between 1→4 linked glucose, and contains a small amount of 1,6-linked glucose, which was in the branched chain. In vitro HepG2, 3T3-L1, and L6 cells were used to assess cellular glucose consumption and cellular glucose uptake by glucose oxidase, and the transport of 2-NBDG fluorescence probe results showed that H-1-2 could clearly increase glucose uptake and utilization in muscle and adipose cells, which is beneficial to screen for in the discovery of anti-diabetes lead compounds. H-1-2 was labeled with radioisotopes ((99m)Tc-pertechnetate). (99m)Tc-labeled-H-1-2 was performed by SPECT/CT analysis images after oral administration in rats. At 4 h post ingestion, about 50% of the radioactivity was observed in the intestine. No significant radioactivity was found in the heart, liver, and kidney, conjecturing that absorption of (99m)Tc-labeled H-1-2 might, via intestinal mucosa, be absorbed into systemic circulation. This problem, as to whether the polysaccharide is absorbed orally, will need further examination.

  13. Differential glucose uptake in quadriceps and other leg muscles during one-legged dynamic submaximal knee-extension exercise

    Directory of Open Access Journals (Sweden)

    Kari eKalliokoski

    2011-10-01

    Full Text Available One-legged dynamic knee-extension exercise (DKE is a widely used model to study the local cardiovascular and metabolic responses to exercise of the quadriceps muscles. In this study, we explored the extent to which different muscles of the quadriceps are activated during exercise using positron emission tomography (PET determined uptake of [18F]-fluoro-deoxy-glucose (GU during DKE. Five healthy male subjects performed DKE at 25 W for 35 min and both the contracting and contralateral resting leg were scanned with PET from mid-thigh and distally. On average, exercise GU was the highest in the vastus intermedius (VI and lowest in the vastus lateralis (VL (VI vs VL, p<0.05, whereas the coefficient of variation was highest in VL (VL vs VI, p<0.05. Coefficient of variation between the mean values of the four QF muscles in the exercising leg was 35±9%. Compared to mean GU in QF (=100%, GU was on average 73% in VL, 84% in rectus femoris, 115% in vastus medialis, and 142% in VI. Variable activation of hamstring muscles and muscles of the lower leg was also observed. These results show that GU of different muscles of quadriceps muscle group as well as between individuals vary greatly during DKE, and suggests that muscle activity is not equal between quadriceps muscles in this exercise model. Furthermore, posterior thigh muscles and lower leg muscles are more active than hitherto thought even during this moderate exercise intensity.

  14. 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.

  15. Absence of RIP140 reveals a pathway regulating glut4-dependent glucose uptake in oxidative skeletal muscle through UCP1-mediated activation of AMPK.

    Directory of Open Access Journals (Sweden)

    Asmaà Fritah

    Full Text Available Skeletal muscle constitutes the major site of glucose uptake leading to increased removal of glucose from the circulation in response to insulin. Type 2 diabetes and obesity are often associated with insulin resistance that can be counteracted by exercise or the use of drugs increasing the relative proportion of oxidative fibers. RIP140 is a transcriptional coregulator with a central role in metabolic tissues and we tested the effect of modulating its level of expression on muscle glucose and lipid metabolism in two mice models. Here, we show that although RIP140 protein is expressed at the same level in both oxidative and glycolytic muscles, it inhibits both fatty acid and glucose utilization in a fiber-type dependent manner. In RIP140-null mice, fatty acid utilization increases in the extensor digitorum longus and this is associated with elevated expression of genes implicated in fatty acid binding and transport. In the RIP140-null soleus, depletion of RIP140 leads to increased GLUT4 trafficking and glucose uptake with no change in Akt activity. AMPK phosphorylation/activity is inhibited in the soleus of RIP140 transgenic mice and increased in RIP140-null soleus. This is associated with increased UCP1 expression and mitochondrial uncoupling revealing the existence of a signaling pathway controlling insulin-independent glucose uptake in the soleus of RIP140-null mice. In conclusion, our findings reinforce the participation of RIP140 in the maintenance of energy homeostasis by acting as an inhibitor of energy production and particularly point to RIP140 as a promising therapeutic target in the treatment of insulin resistance.

  16. Mental stress and cognitive performance do not increase overall level of cerebral O2 uptake in humans

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1992-01-01

    We measured cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral lactate output during rest, during the execution of mental arithmetic, and during mental stress induced by physical and psychological annoyance. Measurements were performed in healthy volunteers by use...... activity. During mental arithmetic and mental stress, cerebral lactate output increased by 207 and 344%, respectively, but because of large individual variations in the measured responses, the elevations reached statistical significance only during mental arithmetic....... stress induced a slight but highly significant (P less than 0.002) 6% reduction in global CMRO2. This finding is in contrast to results from earlier investigations and contradicts the generally accepted notion of an association between mental arousal and a diffuse upregulation of cerebral synaptic...

  17. Positron emission tomography assessment of cerebral glucose metabolic rates in autism spectrum disorder and schizophrenia.

    Science.gov (United States)

    Mitelman, Serge A; Bralet, Marie-Cecile; Mehmet Haznedar, M; Hollander, Eric; Shihabuddin, Lina; Hazlett, Erin A; Buchsbaum, Monte S

    2018-04-01

    Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered 18 fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest. Metabolic rates were compared between three diagnostic groups using univariate and multivariate repeated-measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus, amygdala and medial thalamic nuclei; rates were increased in the occipital cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects metabolic rates were decreased in the parietal lobe, frontal premotor and eye-fields areas, and amygdala; rates were increased in the posterior cingulate, occipital cortex, hippocampus and basal ganglia. In relation to controls, subjects with ASD and schizophrenia showed opposite changes in metabolic rates in the primary motor and somatosensory cortex, anterior cingulate and hypothalamus; similar changes were found in prefrontal and occipital cortices, inferior parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD appear to be associated with a similar pattern of metabolic abnormalities in the social brain. Divergent maladaptive trade-offs, as postulated by the diametrical hypothesis of their evolutionary relationship, may involve a more circumscribed set of anterior cingulate, motor and somatosensory regions and the specific cognitive functions they subserve.

  18. Gadd45b prevents autophagy and apoptosis against rat cerebral neuron oxygen-glucose deprivation/reperfusion injury.

    Science.gov (United States)

    He, Guoqian; Xu, Wenming; Tong, Linyan; Li, Shuaishuai; Su, Shiceng; Tan, Xiaodan; Li, Changqing

    2016-04-01

    Autophagic (type II) cell death has been suggested to play pathogenetic roles in cerebral ischemia. Growth arrest and DNA damage response 45b (Gadd45b) has been shown to protect against rat brain ischemia injury through inhibiting apoptosis. However, the relationship between Gadd45b and autophagy in cerebral ischemia/reperfusion (I/R) injury remains uncertain. The aim of this study is to investigate the effect of Gadd45b on autophagy. We adopt the oxygen-glucose deprivation and reperfusion (OGD/R) model of rat primary cortex neurons, and lentivirus interference used to silence Gadd45b expression. Cell viability and injury assay were performed using CCK-8 and LDH kit. Autophagy activation was monitored by expression of ATG5, LC3, Beclin-1, ATG7 and ATG3. Neuron apoptosis was monitored by expression of Bcl-2, Bax, cleaved caspase3, p53 and TUNEL assay. Neuron neurites were assayed by double immunofluorescent labeling with Tuj1 and LC3B. Here, we demonstrated that the expression of Gadd45b was strongly up-regulated at 24 h after 3 h OGD treatment. ShRNA-Gadd45b increased the expression of autophagy related proteins, aggravated OGD/R-induced neuron cell apoptosis and neurites injury. ShRNA-Gadd45b co-treatment with autophagy inhibitor 3-methyladenine (3-MA) or Wortmannin partly inhibited the ratio of LC3II/LC3I, and slightly ameliorated neuron cell apoptosis under OGD/R. Furthermore, shRNA-Gadd45b inhibited the p-p38 level involved in autophagy, but increased the p-JNK level involved in apoptosis. ShRNA-Gadd45b co-treatment with p38 inhibitor obviously induced autophagy. ShRNA-Gadd45b co-treatment with JNK inhibitor alleviated neuron cell apoptosis. In conclusion, our data suggested that Gadd45b inhibited autophagy and apoptosis under OGD/R. Gadd45b may be a common regulatory protein to control autophagy and apoptosis.

  19. 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

  20. Increased fluoro-deoxy-D-glucose uptake on positron emission tomography-computed tomography postbronchoalveolar lavage: a potential cause of radiologic misinterpretation.

    LENUS (Irish Health Repository)

    Leong, Sum

    2011-08-01

    Cytologic analysis of bronchoalveolar lavage (BAL) fluid is used for lung cancer diagnosis. We describe a patient with a history of rectal carcinoma who presented with a new lung mass. BAL was performed, with positron emission tomography-computed tomography the following day. There was mildly increased fluoro-deoxy-D-glucose uptake in areas of the lung parenchyma with new ground-glass opacification. This created ambiguity in staging, clarified 2 weeks later by a computed tomography showing complete resolution of the ground-glass opacity. Clinicians should be aware that BAL may cause increased pulmonary fluoro-deoxy-D-glucose uptake, making accurate radiologic interpretation problematic. We suggest that to optimize positron emission tomography-computed tomography, studies should not be performed within 24 hours of BAL.

  1. Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro

    DEFF Research Database (Denmark)

    Pedersen, M W; Holm, S; Lund, E L

    2001-01-01

    We examined the relationship between (18)F- labeled 2-fluro-2-deoxy-d-glucose (FDG) uptake, and expression of glucose transporters (GLUTs) in two human small-cell lung cancer (SCLC) lines CPH 54A and CPH 54B. Changes in the expression of GLUTs and vascular endothelial growth factor (VEGF) during 12......-, 18-, and 24 hours of severe hypoxia in vivo (xenografts) and in vitro (cell cultures) were recorded for both tumor lines. The two SCLC lines are subpopulations of the same patient tumor. In spite of their common genomic origin they represent consistently different metabolic and microenvironmental...... phenotypes as well as treatment sensitivities. There were higher levels of Glut-1 protein in 54B and a correspondingly higher FDG uptake in this tumor line (P

  2. Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

    International Nuclear Information System (INIS)

    Nguyen, Xuan Canh; Nguyen, Van Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

    2014-01-01

    To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUV pt ), maxSUV of whole-body tumors (maxSUV wb ) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSCLC were enrolled. Seventeen patients had Stage IIIA, 21 Stage IIIB, and 45 Stage IV. maxSUV pt , maxSUV wb , sumaxSUV, age, gender, tumor-cell type, T stage, N stage, overall stage, primary tumor size, and specific treatment were analyzed for correlation with overall survival. Median follow-up duration was 13 months. Fifty patients were dead during a median follow-up time of 11 months and 33 patients were alive with a median time of 15 months. Univariate analysis revealed that overall survival was significantly correlated with sumaxSUV (≥35 vs. <35, P = 0.004), T stage (T4 vs. T1-T3, P = 0.025), overall stage (IV vs. III, P = 0.002), gender (male vs. female, P = 0.029) and specific treatment (no vs. yes, P = 0.011). maxSUV pt and maxSUV wb were not correlated with overall survival with P value of 0.139 and 0.168, respectively. Multivariate analysis identified sumaxSUV, T stage, gender, and specific treatment as independent prognostic indicators. Patients with a sumaxSUV of ≥35 were 1.921 times more likely to die than those with a sumaxSUV of < 35 (P = 0.047). Median survival time was 14 months for patients with sumaxSUV ≥ 35 compared with 20 months for those with sumaxSUV < 35. In patients with metastatic NSCLC, sumaxSUV with cut-off of 35 was much more significant for survival prognosis (P = 0.021). sumaxSUV is a new prognostic measure, independent of tumor stage, gender, and specific treatment in advanced NSCLC. sumaxSUV may be better than maxSUV pt and maxSUV wb in

  3. Identification of plant extracts with potential antidiabetic properties: effect on human peroxisome proliferator-activated receptor (PPAR), adipocyte differentiation and insulin-stimulated glucose uptake

    DEFF Research Database (Denmark)

    Christensen, Kathrine B; Minet, Ariane; Svenstrup, Henrik

    2009-01-01

    , and their use is associated with several side effects. Partial PPARgamma agonists appear to be associated with fewer side effects but may still confer the desired insulin sensitizing action. Extracts from common medicinal/food plants were tested in a screening platform comprising a series of bioassays...... and stimulating insulin-dependent glucose uptake with no or little effect on adipocyte differentiation warranting further studies and characterization. Copyright (c) 2009 John Wiley & Sons, Ltd....

  4. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    OpenAIRE

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic ac...

  5. Feasibility of direct mapping of cerebral fluorodeoxy-D-glucose metabolism in situ at subcellular resolution using soft X-ray fluorescence.

    Science.gov (United States)

    Poitry-Yamate, Carole; Gianoncelli, Alessandra; Kaulich, Burkhard; Kourousias, George; Magill, Arthur W; Lepore, Mario; Gajdosik, Vincent; Gruetter, Rolf

    2013-08-01

    Glucose metabolism is difficult to image with cellular resolution in mammalian brain tissue, particularly with (18) fluorodeoxy-D-glucose (FDG) positron emission tomography (PET). To this end, we explored the potential of synchrotron-based low-energy X-ray fluorescence (LEXRF) to image the stable isotope of fluorine (F) in phosphorylated FDG (DG-6P) at 1 μm(2) spatial resolution in 3-μm-thick brain slices. The excitation-dependent fluorescence F signal at 676 eV varied linearly with FDG concentration between 0.5 and 10 mM, whereas the endogenous background F signal was undetectable in brain. To validate LEXRF mapping of fluorine, FDG was administered in vitro and in vivo, and the fluorine LEXRF signal from intracellular trapped FDG-6P over selected brain areas rich in radial glia was spectrally quantitated at 1 μm(2) resolution. The subsequent generation of spatial LEXRF maps of F reproduced the expected localization and gradients of glucose metabolism in retinal Müller glia. In addition, FDG uptake was localized to periventricular hypothalamic tanycytes, whose morphological features were imaged simultaneously by X-ray absorption. We conclude that the high specificity of photon emission from F and its spatial mapping at ≤1 μm resolution demonstrates the ability to identify glucose uptake at subcellular resolution and holds remarkable potential for imaging glucose metabolism in biological tissue. Copyright © 2012 Wiley Periodicals, Inc.

  6. Involvement of the Niacin Receptor GPR109a in the LocalControl of Glucose Uptake in Small Intestine of Type 2Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Tung Po Wong

    2015-09-01

    Full Text Available Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM, an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.

  7. Effects of single and repetitive spreading depression on cerebral blood flow and glucose metabolism in cats: a PET study.

    Science.gov (United States)

    Kuge, Y; Hasegawa, Y; Yokota, C; Minematsu, K; Hashimoto, N; Miyake, Y; Yamaguchi, T

    2000-06-15

    To clarify the effects of spreading depression (SD) on cerebral circulation and metabolism, we elicited a single or repetitive episode of SD and evaluated CBF and CMRglc three-dimensionally in normal cats (n=4, in each group) using a high-resolution positron emission tomography (PET) scanner. SD was evoked by applying KCl to the left occipital cortex. We then monitored DC potential changes with tungsten electrodes inserted into the left temporal cortex. CBF was measured twice before and three times (immediately, 30-60 min, and 60-120 min) following KCl application using [15O]H(2)O, and CMRglc was determined using 2-[18F]fluoro-2-deoxy-D-glucose immediately following the last CBF measurement. The following results were obtained: (1) a single episode of SD produced a temporary CBF increase, followed by a long-lasting hypoperfusion in the cortex, with no significant changes to CBF observed in the subcortex; (2) no significant CMRglc changes were observed in either cortical or subcortical regions following a single episode of SD; (3) a flow-metabolism uncoupling was observed in the cortical regions concurrently with persistent hypoperfusion; (4) repetitive SD produced significant CBF changes in the cortex; and (5) the cortical CMRglc increased as a result of repeated episodes of SD, with no significant changes observed in the subcortex. Thus, we succeeded in determining three-dimensionally the effects of single and repetitive SD on CBF and CMRglc in cats using a high-resolution PET scanner. The present study provides the first direct evidence of CBF-CMRglc uncoupling occurring concurrently with persistent hypoperfusion following SD.

  8. Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

    Science.gov (United States)

    Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline Gonçalves; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia M

    2017-07-01

    DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases. Copyright © 2016. Published by Elsevier Ltd.

  9. Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

    International Nuclear Information System (INIS)

    Tsukahara, Tamotsu; Haniu, Hisao; Matsuda, Yoshikazu

    2013-01-01

    Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance

  10. Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsukahara, Tamotsu, E-mail: ttamotsu@shinshu-u.ac.jp [Department of Integrative Physiology and Bio-System Control, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Haniu, Hisao [Department of Orthopedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan)

    2013-04-12

    Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance.

  11. Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions

    Directory of Open Access Journals (Sweden)

    Lingling Han

    2015-01-01

    Full Text Available This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA- induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4, AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase (ACC, and uncoupling protein 3 (UCP3 were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9 and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM, P<0.05 and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min, P<0.05. The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (all P<0.05, but those in the 10−9 and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (all P<0.05. In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation.

  12. Oxidovanadium(IV) sulfate-induced glucose uptake in HepG2 cells through IR/Akt pathway and hydroxyl radicals.

    Science.gov (United States)

    Zhao, Qian; Chen, Deliang; Liu, Pingsheng; Wei, Taotao; Zhang, Fang; Ding, Wenjun

    2015-08-01

    The insulin-mimetic and anti-diabetic properties of vanadium and related compounds have been well documented both in vitro and in vivo. However, the molecular basis of the link between vanadium and the insulin signaling pathway in diabetes mellitus is not fully described. We investigated the effects of reactive oxygen species (ROS) induced by oxidovanadium(IV) sulfate (VOSO4) on glucose uptake and the insulin signaling pathway in human hepatoma cell line HepG2. Exposure of cells to VOSO4 (5-50 μM) resulted in an increase in glucose uptake, insulin receptor (IR) and protein kinase B (Akt) phosphorylation and intracellular ROS generation. Using Western blot, we found that catalase and sodium formate, but not superoxide dismutase, prevented the increase of hydroxyl radical (·OH) generation and significantly decreased VOSO4-induced IR and Akt phosphorylation. These results suggest that VOSO4-induced ·OH radical, which is a signaling species, promotes glucose uptake via the IR/Akt signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    Science.gov (United States)

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

  14. Effect of steeping temperature on antioxidant and inhibitory activities of green tea extracts against α-amylase, α-glucosidase and intestinal glucose uptake.

    Science.gov (United States)

    Liu, Shuyuan; Ai, Zeyi; Qu, Fengfeng; Chen, Yuqiong; Ni, Dejiang

    2017-11-01

    The objective of the present study was to evaluate the effect of steeping temperature on the biological activities of green tea, including the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacity, α-glucosidase and α-amylase inhibitory activities, and glucose uptake inhibitory activity in Caco-2 cells. Results showed that, with increasing extraction temperature, the polyphenol content increased, which contributed to enhance antioxidant activity and inhibitory effects on α-glucosidase and α-amylase. Green tea steeped at 100°C showed the highest DPPH radical-scavenging activity and inhibitory effects on α-glucosidase and α-amylase activities with EC 50 or IC 50 values of 6.15μg/mL, 0.09mg/mL, and 6.31mg/mL, respectively. However, the inhibitory potential on glucose uptake did not show an upward trend with increasing extraction temperature. Green tea steeped at 60°C had significantly stronger glucose uptake inhibitory activity (ptea. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Saponarin activates AMPK in a calcium-dependent manner and suppresses gluconeogenesis and increases glucose uptake via phosphorylation of CRTC2 and HDAC5.

    Science.gov (United States)

    Seo, Woo-Duck; Lee, Ji Hae; Jia, Yaoyao; Wu, Chunyan; Lee, Sung-Joon

    2015-11-15

    This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did not directly interact with the AMPK protein. Instead, saponarin increased intracellular calcium levels and induced AMPK phosphorylation, which was diminished by co-stimulation with STO-609, an inhibitor of CAMKKβ. Transcription of hepatic gluconeogenesis genes was upregulated by nuclear translocation of CRTC2 and HDAC5, coactivators of CREB and FoxO1 transcription factors, respectively. This nuclear translocation was inhibited by increased phosphorylation of CRTC2 and HDAC5 by saponarin-induced AMPK in HepG2 cells and suppression of CREB and FoxO1 transactivation activities in cells stimulated by saponarin. The results from a chromatin immunoprecipitation assay confirmed the reduced binding of CRTC2 on the PEPCK and G6Pase promoters. In TE671 cells, AMPK phosphorylated HDAC5, which suppressed nuclear penetration and upregulated GLUT4 transcription, leading to enhanced glucose uptake. Collectively, these results suggest that saponarin activates AMPK in a calcium-dependent manner, thus regulating gluconeogenesis and glucose uptake. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Plasma levels of leptin, omentin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26 and adiponectin before and after oral glucose uptake in slim adults

    Directory of Open Access Journals (Sweden)

    Schäffler Andreas

    2007-02-01

    Full Text Available Abstract Background Adipose tissue secreted proteins are collectively named adipocytokines and include leptin, adiponectin, resistin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26 and omentin. Several of these adipocytokines influence insulin sensitivity and glucose metabolism and therefore systemic levels may be affected by oral glucose uptake. Whereas contradictory results have been published for leptin and adiponectin, resistin has not been extensively investigated and no reports on omentin and CORS-26 do exist. Methods Therefore the plasma levels of these proteins before and 120 min after an oral glucose load were analyzed in 20 highly-insulin sensitive, young adults by ELISA or immunoblot. Results Circulating leptin was reduced 2 h after glucose uptake whereas adiponectin and resistin levels are not changed. Distribution of adiponectin and CORS-26 isoforms were similar before and after glucose ingestion. Omentin is highly abundant in plasma and immunoblot analysis revealed no alterations when plasma levels before and 2 h after glucose intake were compared. Conclusion Taken together our data indicate that only leptin is reduced by glucose uptake in insulin-sensitive probands whereas adiponectin and resistin are not altered. CORS-26 was demonstrated for the first time to circulate as high molecular weight form in plasma and like omentin was not influenced by oral glucose load. Omentin was shown to enhance insulin-stimulated glucose uptake but systemic levels are not correlated to postprandial blood glucose.

  17. Prediction of prognosis to concurrent chemo-radiotherapy by standardized uptake value of 2[{sup 18}F] fluoro-2-deoxy-d-glucose for nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Wook; Im, Ki Chun; Nam, Soon Yuhl [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)] (and others)

    2005-03-15

    To prospectively evaluate the use of positron emission tomography with the glucose analog fluoro-deoxyglucose (FDG-PET) to predict disease-free survival (DFS) after concurrent chemo-radiotherapy (CCRT) in patients with non-disseminated nasopharyngeal carcinoma (NPC). We studied 41 patients with non-disseminated NPC scheduled to undergo platinum-based CCRT were eligible for this study. Patients were studied by FDG-PET prior to the CCRT. FDG uptake of tumors were measured with the maximal standardized uptake value (SUV). Complete response rate was 100%. In ten patients who presented with any component of treatment failure, the median SUV{sub max} was 8.55 (range: 2.49 {approx} 14.81) in any component of failure and the median SUV{sub max} was 6.48 (range: 2.31 {approx} 26.07) in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year DFS (51% {nu} 91%, {rho} = 0.0070) compared with patients having low uptake tumors. FDG uptake, as measured by the SUV, has potential value in predicting DFS in NPC treated by CCRT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.

  18. Effects of exosomes from LPS-activated macrophages on adipocyte gene expression, differentiation, and insulin-dependent glucose uptake.

    Science.gov (United States)

    De Silva, Nicolás; Samblas, Mirian; Martínez, J Alfredo; Milagro, Fermín I

    2018-03-20

    Obesity is usually associated with low-grade inflammation, which determines the appearance of comorbidities like atherosclerosis and insulin resistance. Infiltrated macrophages in adipose tissue are partly responsible of this inflammatory condition. Numerous studies point to the existence of close intercommunication between macrophages and adipocytes and pay particular attention to the proinflammatory cytokines released by both cell types. However, it has been recently described that in both, circulation and tissue level, there are extracellular vesicles (including microvesicles and exosomes) containing miRNAs, mRNAs, and proteins that can influence the inflammatory response. The objective of the present research is to investigate the effect of exosomes released by lipopolysaccharide (LPS)-activated macrophages on gene expression and cell metabolism of adipocytes, focusing on the differential exosomal miRNA pattern between LPS- and non-activated macrophages. The results show that the exosomes secreted by the macrophages do not influence the preadipocyte-to-adipocyte differentiation process, fat storage, and insulin-mediated glucose uptake in adipocytes. However, exosomes induce changes in adipocyte gene expression depending on their origin (LPS- or non-activated macrophages), including genes such as CXCL5, SOD, TNFAIP3, C3, and CD34. Some of the pathways or metabolic processes upregulated by exosomes from LPS-activated macrophages are related to inflammation (complement activation, regulation of reactive oxygen species, migration and activation of leukocyte, and monocyte chemotaxis), carbohydrate catabolism, and cell activation. miR-530, chr9_22532, and chr16_34840 are more abundant in exosomes from LPS-activated macrophages, whereas miR-127, miR-143, and miR-486 are more abundant in those secreted by non-activated macrophages.

  19. Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles.

    Science.gov (United States)

    Kolnes, Anders J; Birk, Jesper B; Eilertsen, Einar; Stuenæs, Jorid T; Wojtaszewski, Jørgen F P; Jensen, Jørgen

    2015-02-01

    Epinephrine increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown, and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated in condition with decreased GS activation. Saline or epinephrine (0.02 mg/100 g rat) was injected subcutaneously in Wistar rats (∼130 g) with low (24-h-fasted), normal (normal diet), and high glycogen content (fasted-refed), and epitrochlearis muscles were removed after 3 h and incubated ex vivo, eliminating epinephrine action. Epinephrine injection reduced glycogen content in epitrochlearis muscles with high (120.7 ± 17.8 vs. 204.6 ± 14.5 mmol/kg, P muscles with low glycogen (90.0 ± 5.0 vs. 102.8 ± 7.8 mmol/kg, P = 0.17). In saline-injected rats, GS phosphorylation at sites 2+2a, 3a+3b, and 1b was higher and GS activity lower in muscles with high compared with low glycogen. GS sites 2+2a and 3a+3b phosphorylation decreased and GS activity increased in muscles where epinephrine decreased glycogen content; these parameters were unchanged in epitrochlearis from fasted rats where epinephrine injection did not decrease glycogen content. Incubation with insulin decreased GS site 3a+3b phosphorylation independently of glycogen content. Insulin-stimulated glucose uptake was increased in muscles where epinephrine injection decreased glycogen content. In conclusion, epinephrine stimulates glycogenolysis in epitrochlearis muscles with normal and high, but not low, glycogen content. Epinephrine-stimulated glycogenolysis decreased GS phosphorylation and increased GS activity. These data for the first time document direct regulation of GS phosphorylation by glycogen content. Copyright © 2015 the American Physiological Society.

  20. Bavachin from Psoralea corylifolia Improves Insulin-Dependent Glucose Uptake through Insulin Signaling and AMPK Activation in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Hyejin Lee

    2016-04-01

    Full Text Available The fruit of Psoralea corylifolia L. (Fabaceae (PC, known as “Bo-Gol-Zhee” in Korea has been used as traditional medicine. Ethanol and aqueous extracts of PC have an anti-hyperglycemic effect by increasing plasma insulin levels and decreasing blood glucose and total plasma cholesterol levels in type 2 diabetic rats. In this study, we purified six compounds from PC and investigated their anti-diabetic effect. Among the purified compounds, bavachin most potently accumulated lipids during adipocyte differentiation. Intracellular lipid accumulation was measured by Oil Red-O (ORO cell staining to investigate the effect of compounds on adipogenesis. Consistently, bavachin activated gene expression of adipogenic transcriptional factors, proliferator-activated receptorγ (PPARγ and CCAAT/enhancer binding protein-α (C/EBPα. Bavachin also increased adiponectin expression and secretion in adipocytes. Moreover, bavachin increased insulin-induced glucose uptake by differentiated adipocytes and myoblasts. In differentiated adipocytes, we found that bavachin enhanced glucose uptake via glucose transporter 4 (GLUT4 translocation by activating the Akt and 5′AMP-activated protein kinase (AMPK pathway in the presence or absence of insulin. These results suggest that bavachin from Psoralea corylifolia might have therapeutic potential for type 2 diabetes by activating insulin signaling pathways.

  1. Antidiabetic Activity of Pterospermum acerifolium Flowers and Glucose Uptake Potential of Bioactive Fraction in L6 Muscle Cell Lines with Its HPLC Fingerprint

    Directory of Open Access Journals (Sweden)

    Rathinavelusamy Paramaguru

    2014-01-01

    Full Text Available The present study was designed to estimate the detailed antidiabetic activity of Pterospermum acerifolium (L. Willd flowers. In vitro alpha amylase inhibition study was carried out on 50% ethanol extract of flowers (PAFEE and its various fractions. The active ethyl acetate fraction (PAFEF was subfractionated into three subfractions (PAFE1, PAFE2, and PAFE3 and subjected to acute toxicity studies followed by antidiabetic screening in vivo by streptozotocin-nicotinamide induced type II diabetes. Diabetic animals treated with PAFE2 (30 mg/kg reduced the levels of fasting blood glucose, significantly (P<0.001 compared to that of diabetic control animals. Histological studies on drug treated groups did not show remarkable positive changes in β-cells. PAFE2 showed 32.6±1.93% glucose uptake over control and, in the presence of PI3K inhibitor wortmannin, declined to 13.7±2.51%. HPLC analysis of PAFE2 reveals the presence of quercetin and apigenin as major constituents and both are inhibiting the glycogen phosphorylase enzyme in molecular modelling studies. The study evidenced strongly that the probable glucose lowering mechanism of action of active subfraction PAFE2 is by increasing the glucose uptake in peripheral tissues and by inhibition of gluconeogenesis.

  2. Persimmon Tannin Decreased the Glycemic Response through Decreasing the Digestibility of Starch and Inhibiting α-Amylase, α-Glucosidase, and Intestinal Glucose Uptake.

    Science.gov (United States)

    Li, Kaikai; Yao, Fen; Du, Jing; Deng, Xiangyi; Li, Chunmei

    2018-02-21

    Regulation of postprandial blood glucose levels is an effective therapeutic proposal for type 2 diabetes treatment. In this study, the effect of persimmon tannin on starch digestion with different amylose levels was investigated both in vitro and in vivo. Oral administration of persimmon tannin-starch complexes significantly suppressed the increase of blood glucose levels and the area under the curve (AUC) in a dose-dependent manner compared with starch treatment alone in an in vivo rat model. Further study proved that persimmon tannin could not only interact with starch directly but also inhibit α-amylase and α-glucosidase strongly, with IC 50 values of 0.35 and 0.24 mg/mL, separately. In addition, 20 μg/mL of persimmon tannin significantly decreased glucose uptake and transport in Caco-2 cells model. Overall, our data suggested that persimmon tannin may alleviate postprandial hyperglycemia through limiting the digestion of starch as well as inhibiting the uptake and transport of glucose.

  3. Effect of magnesium treatment and glucose levels on delayed cerebral ischemia in patients with subarachnoid hemorrhage: a substudy of the Magnesium in Aneurysmal Subarachnoid Haemorrhage trial (MASH-II).

    Science.gov (United States)

    Leijenaar, Jolien F; Dorhout Mees, Sanne M; Algra, Ale; van den Bergh, Walter M; Rinkel, Gabriel J E

    2015-10-01

    Magnesium treatment did not improve outcome in patients with aneurysmal subarachnoid haemorrhage in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. We hypothesized that high glucose levels may have offset a potential beneficial effect to prevent delayed cerebral ischemia. We investigated if magnesium treatment led to less delayed cerebral ischemia and if glucose levels interacted with magnesium treatment in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. To investigate the effect of magnesium treatment on occurrence of delayed cerebral ischemia and the interaction between glucose levels and magnesium treatment in subarachnoid hemorrhage patients. The Magnesium in Aneurysmal Subarachnoid Haemorrhage was a phase III randomized placebo-controlled trial assessing the effect of magnesium sulphate on clinical outcome in aneurysmal subarachnoid hemorrhage patients. For the current study, we included only the patients admitted to the University Medical Centre-Utrecht. We calculated hazard ratios for occurrence of delayed cerebral ischemia in patients treated with magnesium vs. placebo for the entire study population, and separately in the subgroups of patients with high and low mean fasting and mean daily glucose levels until onset of delayed cerebral ischemia. We used the cross-product of magnesium and glucose in the regression analysis to evaluate whether an interaction between magnesium and glucose existed. We included 616 patients: 307 received magnesium and 309 placebo; 156 patients had delayed cerebral ischemia. Hazard ratio for magnesium on occurrence of delayed cerebral ischemia was 1·0 (95% confidence interval: 0·7-1·4). Results were similar in patients with low or high fasting or daily glucose levels. We found no interactions between magnesium treatment and high fasting (P = 0·54) and daily glucose (P = 0·60). Magnesium treatment did not reduce the risk of delayed cerebral ischemia in patients with aneurysmal

  4. First-pass uptake and oxidation of glucose by the splanchnic tissue in young goats fed soy protein-based milk diets with or without amino acid supplementation: glucose metabolism in goat kids after soy feeding.

    Science.gov (United States)

    Schönhusen, U; Junghans, P; Flöter, A; Steinhoff-Wagner, J; Görs, S; Schneider, F; Metges, C C; Hammon, H M

    2013-04-01

    The study was designed to examine whether feeding soy protein isolate as partial replacement of casein (CN) affects glucose metabolism in young goats and whether effects may be ameliorated by supplementation of those AA known to be lower concentrated in soy than in CN. Goat kids (d 20 of age) were fed comparable milk protein diets, in which 50% of the crude protein was either CN (control, CON), soy protein isolate (SPI), or soy protein isolate supplemented with AA (SPIA) for 43 d (n=8 per group). On d 62 of age, a single bolus dose of d-[(13)C6]glucose (10mg/kg of BW) was given with the morning diet, and simultaneously, a single bolus dose of d-[6,6-(2)H2]glucose (5mg/kg of BW) was injected into a jugular vein. Blood samples were collected between -30 and +420 min relative to the tracer administration to measure the (13)C and (2)H enrichments of plasma glucose and the (13)C enrichment of blood CO2. Glucose first-pass uptake by the splanchnic tissues was calculated from the rate of appearance of differentially labeled glucose tracer in plasma. Glucose oxidation was calculated from (13)C enrichment in blood CO2. In addition, plasma concentrations of triglycerides, nonesterified fatty acids, glucose, insulin, and glucagon were measured. On d 63 of age, kids were killed and jejunal mucosa and liver samples were collected to measure lactase mRNA levels and lactase and maltase activities in the jejunum and activities of pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK) in the liver. Basal plasma glucose concentration tended to be higher in the CON than the SPIA group, whereas basal insulin was higher in the CON group than the SPI and SPIA groups, and glucagon was higher in the CON than the SPIA group. Plasma glucose and insulin concentrations increased during the first hour after feeding, whereas plasma glucagon increased immediately after feeding and after 1h of feeding. First-pass uptake and glucose oxidation were not affected by diet. Maltase

  5. Effects of gamma-rays and glucose analogs on the energy metabolism of a cell line derived from human cerebral glioma

    International Nuclear Information System (INIS)

    Dwarakanath, B.S.

    1991-01-01

    Effects of gamma-rays and glucose analogs, 2-deoxy-D-glucose (2-DG), 5-thio-D-glucose (5-TG) and 3-O-methyl glucose (3-O-MG) on cellular energy metabolism have been studied in a cell line, derived from a human cerebral glioma, by analysing intermediates of glycolysis and some important nucleotides (ATP, NAD etc.) using the technique of isotachophoresis. Gamma-irradiation induced a transient decrease in the nucleotide levels accompanied by an accumulation of sugar phosphates, the nucleotide levels recovering in a few hours post-irradiation. 2-DG inhibited glycolysis and reduced the nucleotide levels of irradiated as well as unirradiated cells in a concentration-dependent manner both in presence and absence of respiration, whereas 5-TG and 3-O M G did not show significant effects in the presence of respiration. Reduced energy status observed with 2-DG under respiratory proficient conditions was completely reversed in 2 hr following its removal, whereas such a recovery was not observed in the absence of respiration. These results have important implications in the energy-linked modifications of tumor radiation response using glucose analogs. (author). 36 refs., 6 figs., 4 tabs

  6. A two-compartment description and kinetic procedure for measuring regional cerebral [11C]nomifensine uptake using positron emission tomography

    International Nuclear Information System (INIS)

    Salmon, E.; Brooks, D.J.; Leenders, K.L.; Turton, D.R.; Hume, S.P.; Cremer, J.E.; Jones, T.; Frackowiak, R.S.

    1990-01-01

    S-[11C]Nomifensine (S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood--brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a free NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its binding potential to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers

  7. Simultaneous glucose and xylose uptake by an acetone/butanol/ethanol producing laboratory Clostridium beijerinckii strain SE-2.

    Science.gov (United States)

    Zhang, Jie; Zhu, Wen; Xu, Haipeng; Li, Yan; Hua, Dongliang; Jin, Fuqiang; Gao, Mintian; Zhang, Xiaodong

    2016-04-01

    Most butanol-producing strains of Clostridium prefer glucose over xylose, leading to a slower butanol production from lignocellulose hydrolysates. It is therefore beneficial to find and use a strain that can simultaneously use both glucose and xylose. Clostridium beijerinckii SE-2 strain assimilated glucose and xylose simultaneously and produced ABE (acetone/butanol/ethanol). The classic diauxic growth behavior was not seen. Similar rates of sugar consumption (4.44 mM glucose h(-1) and 6.66 mM xylose h(-1)) were observed suggesting this strain could use either glucose or xylose as the substrate and it has a similar capability to degrade these two sugars. With different initial glucose:xylose ratios, glucose and xylose were consumed simultaneously at rates roughly proportional to their individual concentrations in the medium, leading to complete utilization of both sugars at the same time. ABE production profiles were similar on different substrates. Transcriptional studies on the effect of glucose and xylose supplementation, however, suggests a clear glucose inhibition on xylose metabolism-related genes is still present.

  8. Cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography in paediatric anti N-methyl-D-aspartate receptor encephalitis: A case series.

    Science.gov (United States)

    Lagarde, Stanislas; Lepine, Anne; Caietta, Emilie; Pelletier, Florence; Boucraut, José; Chabrol, Brigitte; Milh, Mathieu; Guedj, Eric

    2016-05-01

    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a frequent and severe cause of encephalitis in children with potential efficient treatment (immunotherapy). Suggestive clinical features are behavioural troubles, seizures and movement disorders. Prompt diagnosis and treatment initiation are needed to guarantee favourable outcome. Nevertheless, diagnosis may be challenging because of the classical ancillary test (magnetic resonance imaging (MRI), electroencephalogram, standard cerebro-spinal fluid analysis) have limited sensitivity. Currently, immunological analyses are needed for the diagnostic confirmation. In adult patients, some studies suggested a potential role of cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography (FDG-PET) in the evaluation of anti-NMDAR encephalitis. Nevertheless, almost no data exist in paediatric population. We report retrospectively clinical, ancillary tests and cerebral FDG-PET data in 6 young patients (median age=10.5 years, 4 girls) with immunologically confirmed anti-NMDAR encephalitis. Our patients presented classical clinical features of anti-NMDAR encephalitis with severe course (notably four patients had normal MRI). Our series shows the feasibility and the good sensitivity of cerebral FDG-PET (6/6 patients with brain metabolism alteration) in paediatric population. We report some particular features in this population: extensive, symmetric cortical hypometabolism especially in posterior areas; asymmetric anterior focus of hypermetabolism; and basal ganglia hypermetabolism. We found also a good correlation between the clinical severity and the cerebral metabolism changes. Moreover, serial cerebral FDG-PET showed parallel brain metabolism and clinical improvement. Our study reveals the existence of specific patterns of brain metabolism alteration in anti-NMDAR encephalitis in paediatric population. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. Correlation of Glut-1 glucose transporter expression with [{sup 18}F]FDG uptake in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Higashi, Kotaro; Wang, Xiao; Xu, Linfeng; Oguchi, Manabu; Taki, Suzuka; Tonami, Hisao; Yamamoto, Itaru [Department of Radiology, Kanazawa Medical University, Ishikawa (Japan); Ueda, Yoshimichi; Sakurai, Aya; Katsuda, Shogo [Department of Pathology, Kanazawa Medical University, Ishikawa (Japan); Murakami, Manabu [Medical Research Institute, Kanazawa Medical University, Ishikawa (Japan); Seki, Hiroyasu [Department of Radiology, Kanazawa Cardiovascular Hospital, Ishikawa (Japan); Nambu, Yoshihiro [Department of Internal Medicine, Division of Respiratory Disease, Kanazawa Medical University, Ishikawa (Japan)

    2000-12-01

    Positron emission tomography (PET) with [{sup 18}F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [{sup 18}F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [{sup 18}F]FDG PET was performed 40 min after i.v. injection of 185 MBq [{sup 18}F]FDG. For semi-quantitative analysis of [{sup 18}F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P<0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n=7) (2.86%{+-}7.56% and 1.25{+-}0.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n=23) (54.83%{+-}25.64%, P<0.0001, and 3.94{+-}1.93, P=0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n=11, SUV 1.47{+-}0.63; intensities 2 and 3, n=23, SUV 4.78{+-}2.13; P<0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n=34, r=0.658, P<0.01). Overexpression of Glut-1 correlated with high [{sup 18}F]FDG uptake. These findings suggest that Glut

  10. 14C glucose uptake and turnover, a biomarker in benzo(a)pyrene induced lung carcinogenesis: role of curcumin and resveratrol

    International Nuclear Information System (INIS)

    Malhotra, Anshoo; Nair, P.; Dhawan, D.K.

    2010-01-01

    Full text: The aim of the present study was to explore the synergistic potential of curcumin and resveratrol in modulation of glucose metabolism by studying 14 C glucose uptake, turnover in the lung slices and ultra-histoarchitectural changes during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. The mice were segregated into five treatment groups which included group I (normal control), group II (BP treated), group III (BP+curcumin treated), group IV (BP+resveratrol treated) and group V (BP+curcumin+resveratrol treated). Animals in Group II were given a single intraperitoneal injection of Benzo(a)pyrene in corn oil at a dose level of 100mg/Kg body weight. Group III animals were given curcumin orally in drinking water at a dose level of 60 mg /Kg/ body weight, thrice a week. Animals in Group IV were given resveratrol orally at a dose level of 5.7 microgram/ml drinking water, thrice a week. Animals in group V were given a combined treatment of curcumin and resveratrol in a similar manner as was given to group III and group IV animals, respectively. All the animals had free access to the diet and water and the treatments continued for a total duration of 22 weeks. The morphological and ultra-histoachitectural analyses confirmed lung carcinogenesis, in the BP treated mice. Tumor incidence and tumor multiplicity were observed to be 88% and 1.75 respectively in the BP treated mice. A statistically significant increase in the uptake of 14 C glucose was observed in the lung slices of BP treated mice. Further, radiorespirometric analyses of 14 C turnover also showed a significant increase in the lung slices of BP treated mice. The ultra-histoarchitecture of the BP treated mice revealed disruption in cellular integrity along with nuclear deformation. Mitochondria were swollen and cytoplasm appeared granular along with extensive vacuolization. Further, spaces between the endothelium, epithelium and basement membrane indicative of lung injury and edema were observed

  11. Inhibition of protein kinase CbetaII increases glucose uptake in 3T3-L1 adipocytes through elevated expression of glucose transporter 1 at the plasma membrane

    NARCIS (Netherlands)

    Bosch, Remko R.; Bazuine, Merlijn; Wake, Michelle M.; Span, Paul N.; Olthaar, André J.; Schürmann, Annette; Maassen, J. Antonie; Hermus, Ad R. M. M.; Willems, Peter H. G. M.; Sweep, C. G. J.

    2003-01-01

    The mechanism via which diacylglycerol-sensitive protein kinase Cs (PKCs) stimulate glucose transport in insulin-sensitive tissues is poorly defined. Phorbol esters, such as phorbol-12-myristate-13-acetate (PMA), are potent activators of conventional and novel PKCs. Addition of PMA increases the

  12. Measurement of regional cerebral metabolic rate for glucose in the human subject with (F-18)-2-deoxy-2-fluoro-d-glucose and emission computed tomography: validation of the method

    International Nuclear Information System (INIS)

    Phelps, M.E.; Huang, S.C.; Hoffman, E.J.; Selin, C.; Kuhl, D.E.

    1977-01-01

    Tracer techniques and models of in vitro quantitative autoradiography and tissue counting for the measure of regional metabolic rates (rMR) are combined with emission computed tomography (ECT). This approach, Physiologic Tomography (PT), provides atraumatic and analytical measurements of rMR. PT is exemplified with the regional measurement of the cerebral metabolic rate for glucose (CMRGlu) in man with ( 18 F)-2-deoxy-2-fluoro-D-glucose (FDG) and positron ECT. Our model incorporates a k 4 * mediated hydrolysis of FDG-6-PO 4 to FDG which then competes with phosphorylation (k 3 *) of FDG back to FDG-6-PO 4 and reverse transport (k 2 *) back to blood. Although small, k 4 * is found to be significant. The ECAT positron tomograph was used to measure the rate constants (k 1 *→k 4 *), lumped constant (LC), stability, and reproducibility of the model in man. Since these parameters have not been measured for FDG in any species, comparisons are made to values for DG in rat and monkey. Compartmental concentrations of FDG and FDG-6-PO 4 were determined and show that cerebral FDG-6-PO 4 steadily accumulates for about 100 mins, plateaus and then slowly decreases due to hydrolysis. Cerebral blood FDG concentration was determined to be a minor contribution to tissue activity after 10 min. Regional CMRGlu measurements are reproducible to +- 5.5% over 5 hrs. PT allows the in vivo study ofregional biochemistry and physiology in normal and pathophysiologic states in man with a unique and fundamental capability

  13. Calibrated image-derived input functions for the determination of the metabolic uptake rate of glucose with [18F]-FDG PET

    DEFF Research Database (Denmark)

    Christensen, Anders N; Reichkendler, Michala H; Larsen, Rasmus

    2014-01-01

    PURPOSE: We investigated the use of a simple calibration method to remove bias in previously proposed approaches to image-derived input functions (IDIFs) when used to calculate the metabolic uptake rate of glucose (K(m)) from dynamic [(18)F]-FDG PET scans of the thigh. Our objective was to obtain...... nonbiased, low-variance K(m) values without blood sampling. MATERIALS AND METHODS: We evaluated eight previously proposed IDIF methods. K(m) values derived from these IDIFs were compared with Km values calculated from the arterial blood samples (gold standard). We used linear regression to extract...

  14. Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives

    OpenAIRE

    Yap, Angeline; Nishiumi, Shin; Yoshida, Ken-ichi; Ashida, Hitoshi

    2007-01-01

    Some of inositol derivatives have been reported to help the action of insulin stimulating glucose uptake in skeletal muscle cells. Rat L6 myotubes were employed in an attempt to develop an in vitro model system for investigation of the possible insulin-like effect of eight inositol derivatives, namely allo-inositol, d-chiro-inositol l-chiro-inositol, epi-inositol, muco-inositol, myo-inositol, scyllo-inositol and d-pinitol. At a higher concentration of 1 mM seven inositol derivatives other tha...

  15. Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes.

    Science.gov (United States)

    Ohta, Mitsuhiro; Fujinami, Aya; Kobayashi, Norihiro; Amano, Akiko; Ishigami, Akihito; Tokuda, Harukuni; Suzuki, Nobutaka; Ito, Fumitake; Mori, Taisuke; Sawada, Morio; Iwasa, Koichi; Kitawaki, Jo; Ohnishi, Katsunori; Tsujikawa, Muneo; Obayashi, Hiroshi

    2015-07-01

    4-Hydroxyderricin (4HD) and xanthoangelol (XAG) are major components of n-hexane/ethyl acetate (5:1) extract of the yellow-colored stem juice of Angelica keiskei. 4-Hydroxyderricin and XAG have been reported to increase glucose transporter 4 (GLUT4)-dependent glucose uptake in 3T3-L1 adipocytes, but the detailed mechanism of this phenomenon remains unknown. This present study was aimed at clarifying the detailed mechanism by which 4HD and XAG increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes. Both 4HD and XAG increased glucose uptake and GLUT4 translocation to the plasma membrane. 4-Hydroxyderricin and XAG also stimulated the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase. In addition, phosphorylation of liver kinase B1 (LKB1), which acts upstream of AMPK, was also increased by 4HD and XAG treatment. Small interfering RNA knockdown of LKB1 attenuated 4HD- and XAG-stimulated AMPK phosphorylation and suppressed glucose uptake. These findings demonstrate that 4HD and XAG can increase GLUT4-dependent glucose uptake through the LKB1/AMPK signaling pathway in 3T3-L1 adipocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.

  17. Nanoparticle Delivered Human Biliverdin Reductase-Based Peptide Increases Glucose Uptake by Activating IRK/Akt/GSK3 Axis: The Peptide Is Effective in the Cell and Wild-Type and Diabetic Ob/Ob Mice

    Directory of Open Access Journals (Sweden)

    Peter E. M. Gibbs

    2016-01-01

    Full Text Available Insulin’s stimulation of glucose uptake by binding to the IRK extracellular domain is compromised in diabetes. We have recently described an unprecedented approach to stimulating glucose uptake. KYCCSRK (P2 peptide, corresponding to the C-terminal segment of hBVR, was effective in binding to and inducing conformational change in the IRK intracellular kinase domain. Although myristoylated P2, made of L-amino acids, was effective in cell culture, its use for animal studies was unsuitable. We developed a peptidase-resistant formulation of the peptide that was efficient in both mice and cell culture systems. The peptide was constructed of D-amino acids, in reverse order, and blocked at both termini. Delivery of the encapsulated peptide to HepG2 and HSKM cells was confirmed by its prolonged effect on stimulation of glucose uptake (>6 h. The peptide improved glucose clearance in both wild-type and Ob/Ob mice; it lowered blood glucose levels and suppressed glucose-stimulated insulin secretion. IRK activity was stimulated in the liver of treated mice and in cultured cells. The peptide potentiated function of IRK’s downstream effector, Akt-GSK3-(α,β axis. Thus, P2-based approach can be used for improving glucose uptake by cells. Also, it allows for screening peptides in vitro and in animal models for treatment of diabetes.

  18. Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner.

    Science.gov (United States)

    Gietl, Anton F; Warnock, Geoffrey; Riese, Florian; Kälin, Andrea M; Saake, Antje; Gruber, Esmeralda; Leh, Sandra E; Unschuld, Paul G; Kuhn, Felix P; Burger, Cyrill; Mu, Linjing; Seifert, Burkhardt; Nitsch, Roger M; Schibli, Roger; Ametamey, Simon M; Buck, Alfred; Hock, Christoph

    2015-04-01

    Early uptake of [(11)C]-Pittsburgh Compound B (ePiB, 0-6 minutes) estimates cerebral blood flow. We studied ePiB in 13 PiB-negative and 10 PiB-positive subjects with mild cognitive impairment (MCI, n = 23) and 11 PiB-positive and 74 PiB-negative cognitively healthy elderly control subjects (HCS, n = 85) in 6 bilateral volumes of interest: posterior cingulate cortex (PCC), hippocampus (hipp), temporoparietal region, superior parietal gyrus, parahippocampal gyrus (parahipp), and inferior frontal gyrus (IFG) for the associations with cognitive status, age, amyloid deposition, and apolipoprotein E ε4-allele. We observed no difference in ePiB between PiB-positive and -negative subjects and carriers and noncarriers. EPiB decreased with age in PiB-positive subjects in bilateral superior parietal gyrus, bilateral temporoparietal region, right IFG, right PCC, and left parahippocampal gyrus but not in PiB-negative subjects. MCI had lower ePiB than HCS (left PCC, left IFG, and left and right hipp). Lowest ePiB values were found in MCI of 70 years and older, who also displayed high cortical PiB binding. This suggests that lowered regional cerebral blood flow indicated by ePiB is associated with age in the presence but not in the absence of amyloid pathology. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. 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. Cerebra......) min(-1) (P Exercise-induced hypoglycaemia limits the cerebral uptake of glucose, exacerbates exercise, reduces the cerebral metabolic rate of oxygen and attenuates the release of IL-6 from the brain.......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...... blood flow, metabolism and interleukin-6 (IL-6) release were evaluated with the Kety-Schmidt technique. Blood glucose was maintained during the glucose trial, while it decreased from 5.2 +/- 0.1 to 2.9 +/- 0.3 mmol L-1 (mean +/- SE) after 180 min of exercise in the placebo trial with a concomitant...

  20. Nonradioisotope assay of glucose uptake activity in rat skeletal muscle using enzymatic measurement of 2-deoxyglucose 6-phosphate in vitro and in vivo.

    Science.gov (United States)

    Ueyama, A; Sato, T; Yoshida, H; Magata, K; Koga, N

    2000-01-01

    We investigated a nonradioisotope method for the evaluation of glucose uptake activity using enzymatic measurement of 2-deoxyglucose 6-phosphate (2DG6P) content in isolated rat soleus muscle in vitro and in vivo. The 2DG6P content in isolated rat soleus muscle after incubation with 2-deoxyglucose (2DG) was increased in a dose-dependent manner by insulin (ED(50) = 0.6 mU/ml), the maximum response being about 5 times that of the basal content in vitro. This increment was completely abolished by wortmannin (100 nM), with no effect on basal 2DG6P content. An insulin-mimetic compound, vanadium, also increased 2DG6P content in a dose-dependent manner. In isolated soleus muscle of Zucker fa/fa rats, well known as an insulin-resistant model, insulin did not increase 2DG6P content. The 2DG6P content in rat soleus muscle increased after 2DG (3 mmol/kg) injection in vivo, and conversely, the 2DG concentration in plasma was decreased in a dose-dependent manner by insulin (ED(50) = 0.11 U/kg). The maximum response of the accumulation of 2DG6P in soleus muscle was about 4 times that of the basal content. This method could be useful for evaluating glucose uptake (transport plus phosphorylation) activity in soleus muscle in vitro and in vivo without using radioactive materials. Copyright 2000 S. Karger AG, Basel.

  1. AMPK alpha1 activation is required for stimulation of glucose uptake by twitch contraction, but not by H2O2, in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Schjerling, Peter; Viollet, Benoit

    2008-01-01

    into muscle by certain stimuli. In contrast, no clear function has yet been determined for alpha(1) AMPK in skeletal muscle, possibly due to alpha-AMPK isoform signaling redundancy. By applying low-intensity twitch-contraction and H(2)O(2) stimulation to activate alpha(1) AMPK, but not alpha(2) AMPK......, in wildtype and alpha-AMPK transgenic mouse muscles, this study aimed to define conditions where alpha(1) AMPK is required to increase muscle glucose uptake. METHODOLOGY/PRINCIPAL FINDINGS: Following stimulation with H(2)O(2) (3 mM, 20 min) or twitch-contraction (0.1 ms pulse, 2 Hz, 2 min), signaling and 2......-deoxyglucose uptake were measured in incubated soleus muscles from wildtype and muscle-specific kinase-dead AMPK (KD), alpha(1) AMPK knockout or alpha(2) AMPK knockout mice. H(2)O(2) increased the activity of both alpha(1) and alpha(2) AMPK in addition to Akt phosphorylation, and H(2)O(2)-stimulated glucose...

  2. The action of piracetam on 14C-glucose metabolism in normal and posthypoxic rat cerebral cortex slices

    International Nuclear Information System (INIS)

    Domanska-Janik, K.; Zaleska, M.

    1977-01-01

    The stimulating effect of piracetam on the respiration and glycolysis was observed in rat brain cortex slices incubated under oxygen atmosphere. After preincubation of the slices under pure nitrogen atmosphere, piracetam influenced also decarboxylation of the C 1 -glucose carbon, indicating stimulation of the pentose cycle. Any significant effect of piracetam on the lowered by anoxia incorporation of 14 C from U- 14 C-glucose into macromolecular fractions was not observed. The results have supported a protective effect of piracetam against oxygen deficiency, caused mainly by stimulation of metabolic glucose pathways, connected with energy production in CNS. (author)

  3. Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies.

    Directory of Open Access Journals (Sweden)

    Tim D Fryer

    Full Text Available Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO positron emission tomography (PET is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs, two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity.Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI and tetrazolium chloride (TTC staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9, tissue oxygen partial pressure (PtO2 was measured in the ischemic tissue during both control and NBO conditions.As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2.Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging.

  4. Glucose transporter 3 and 1 may facilitate high uptake of 18F-FDG in gastric schwannoma.

    Science.gov (United States)

    Shimada, Yutaka; Sawada, Shigeaki; Hojo, Shozo; Okumura, Tomoyuki; Nagata, Takuya; Nomoto, Kazuhiro; Tsukada, Kazuhiro

    2013-11-01

    Recently, some gastric schwannomas have been reported to have high uptake of FDG. However, Glut-1 was reported to be negative in gastric schwannomas tested. A 64-year-old female patient received a laparoscopic partial gastrectomy for a FDG PET-positive submucosal tumor (SUVmax 6.61). The resected tumor was diagnosed as a benign gastric schwannoma. Glut family immunohistochemical examination revealed diffuse positive expression of Glut-3 and partial positive expression of Glut-1. On the other hand, Glut-2 and Glut-4 expression in the tumor were negative. This case suggested that Glut-3 and Glut-1 expression were facilitators of high FDG uptake in the benign gastric schwannoma.

  5. Genetic variation in ATP5O is associated with skeletal muscle ATP50 mRNA expression and glucose uptake in young twins.

    Directory of Open Access Journals (Sweden)

    Tina Rönn

    Full Text Available BACKGROUND: Impaired oxidative capacity of skeletal muscle mitochondria contribute to insulin resistance and type 2 diabetes (T2D. Furthermore, mRNA expression of genes involved in oxidative phosphorylation, including ATP5O, is reduced in skeletal muscle from T2D patients. Our aims were to investigate mechanisms regulating ATP5O expression in skeletal muscle and association with glucose metabolism, and the relationship between ATP5O single nucleotide polymorphisms (SNPs and risk of T2D. METHODOLOGY/PRINCIPAL FINDINGS: ATP5O mRNA expression was analyzed in skeletal muscle from young (n = 86 and elderly (n = 68 non-diabetic twins before and after a hyperinsulinemic euglycemic clamp. 11 SNPs from the ATP5O locus were genotyped in the twins and a T2D case-control cohort (n = 1466. DNA methylation of the ATP5O promoter was analyzed in twins (n = 22 using bisulfite sequencing. The mRNA level of ATP5O in skeletal muscle was reduced in elderly compared with young twins, both during basal and insulin-stimulated conditions (p<0.0005. The degree of DNA methylation around the transcription start of ATP5O was <1% in both young and elderly twins and not associated with mRNA expression (p = 0.32. The mRNA level of ATP5O in skeletal muscle was positively related to insulin-stimulated glucose uptake (regression coefficient = 6.6; p = 0.02. Furthermore, two SNPs were associated with both ATP5O mRNA expression (rs12482697: T/T versus T/G; p = 0.02 and rs11088262: A/A versus A/G; p = 0.004 and glucose uptake (rs11088262: A/A versus A/G; p = 0.002 and rs12482697: T/T versus T/G; p = 0.005 in the young twins. However, we could not detect any genetic association with T2D. CONCLUSIONS/SIGNIFICANCE: Genetic variation and age are associated with skeletal muscle ATP5O mRNA expression and glucose disposal rate, suggesting that combinations of genetic and non-genetic factors may cause the reduced expression of ATP5O in T2D muscle. These findings propose a role for ATP5O, in

  6. Ameliorative effects of α-lipoic acid on high-fat diet-induced oxidative stress and glucose uptake impairment of T cells.

    Science.gov (United States)

    Cui, Jue; Huang, Dejian; Zheng, Yi

    2016-10-01

    The incidence of obesity and metabolic disease continues to rise, mainly associated with consumption of a high-fat diet (HFD). Previous studies have indicated that HFD could disturb the immune system, leading to immunodeficiency and inflammation. Several mechanisms have been postulated to account for immunodeficiency associated with HFD, one being oxidative stress. To further investigate the effects of HFD on glucose metabolism and proliferative capability of T cells and the protective effects of α-lipoic acid (LA), male C57BL/6J mice were fed a normal chow (10% fat), an HFD (60% fat), an LA supplement (HFD +0.1%LA), and a N-acetyl-L-cysteine supplement (HFD +0.1% NAC) for 10 weeks. Results showed that 10-week HFD increased intracellular reactive oxygen species (ROS) production, induced oxidative stress state formation, inhibited glucose uptake, decreased ATP concentration, reduced proliferative rate, and dampened IL-2 production of T cells of mice. Administration of LA significantly alleviated these changes induced by HFD. These findings reveal that oxidative stress of T cells caused by HFD may be a key factor leading to glucose metabolism reduction and proliferative capability and function impairment of T cells. LA, as a potent agonist, could promote Nrf2 nuclear translocation and up-regulate expression of Nrf2 target genes (Ho-1 and Prdx1), which can eliminate excess ROS and restore redox balance of cells.

  7. Prognostic impact of hexokinase and glucose transporter expressions and clinicopathologic features related to F-18-FDG uptake in esophageal cancer

    NARCIS (Netherlands)

    Schreurs, Liesbeth M; Pultrum, Bareld B; Pavlov, Kirill; Pruim, Jan; Groen, Henk; Hollema, Harry; Plukker, John Theodorus

    39 Background: Elucidation of prognostic predictors based on biological viability may be useful for a better detection of patients with a high risk of relapse or death from esophageal cancer. METHODS: Maximum standardized uptake values (SUVmax) were measured in the preoperative 18F-FDG positron

  8. A glucose transporter can mediate ribose uptake: definition of residues that confer substrate specificity in a sugar transporter.

    Science.gov (United States)

    Naula, Christina M; Logan, Flora J; Logan, Flora M; Wong, Pui Ee; Barrett, Michael P; Burchmore, Richard J

    2010-09-24

    Sugars, the major energy source for many organisms, must be transported across biological membranes. Glucose is the most abundant sugar in human plasma and in many other biological systems and has been the primary focus of sugar transporter studies in eukaryotes. We have previously cloned and characterized a family of glucose transporter genes from the protozoan parasite Leishmania. These transporters, called LmGT1, LmGT2, and LmGT3, are homologous to the well characterized glucose transporter (GLUT) family of mammalian glucose transporters. We have demonstrated that LmGT proteins are important for parasite viability. Here we show that one of these transporters, LmGT2, is a more effective carrier of the pentose sugar d-ribose than LmGT3, which has a 6-fold lower relative specificity (V(max)/K(m)) for ribose. A pair of threonine residues, located in the putative extracellular loops joining transmembrane helices 3 to 4 and 7 to 8, define a filter that limits ribose approaching the exofacial substrate binding pocket in LmGT3. When these threonines are substituted by alanine residues, as found in LmGT2, the LmGT3 permease acquires ribose permease activity that is similar to that of LmGT2. The location of these residues in hydrophilic loops supports recent suggestions that substrate recognition is separated from substrate binding and translocation in this important group of transporters.

  9. Two weeks of metformin treatment induces AMPK dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Treebak, Jonas Thue; Schjerling, Peter

    2014-01-01

    signaling. Methods: Oral doses of metformin or saline treatment were given muscle-specific kinase α2 dead AMPK mice (KD) and wild type (WT) littermates either once or chronically for 2 weeks. Soleus and Extensor Digitorum Longus (EDL) muscles were used for measurements of glucose transport and Western blot...

  10. A novel dual-glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist is neuroprotective in transient focal cerebral ischemia in the rat.

    Science.gov (United States)

    Han, Ling; Hölscher, Christian; Xue, Guo-Fang; Li, Guanglai; Li, Dongfang

    2016-01-06

    Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been shown to be neuroprotective in previous studies in animal models of Alzheimer's or Parkinson's disease. Recently, novel dual-GLP-1/GIP receptor agonists that activate both receptors (DA) were developed to treat diabetes. We tested the protective effects of a novel potent DA against middle cerebral artery occlusion injury in rats and compared it with a potent GLP-1 analog, Val(8)-GLP-1(glu-PAL). Animals were evaluated for neurologic deficit score, infarct volume, and immunohistochemical analyses of the brain at several time points after ischemia. The Val(8)-GLP-1(glu-PAL)-treated and DA-treated groups showed significantly reduced scores of neurological dysfunction, cerebral infarction size, and percentage of TUNEL-positive apoptotic neurons. Furthermore, the expression of the apoptosis marker Bax, the inflammation marker iNOS, and the survival marker Bcl-2 was significantly increased. The DA-treated group was better protected against neurodegeneration than the Val(8)-GLP-1(glu-PAL) group, and the scores of neurological dysfunction, cerebral infarction size, and expression of Bcl-2 were higher, whereas the percentage of TUNEL-positive neurons and the levels of Bax and iNOS were lower in the DA group. DA treatment reduced the infarct volume and improved the functional deficit. It also suppressed the inflammatory response and cell apoptosis after reperfusion. In conclusion, the novel GIP and GLP-1 dual-receptor agonist is more neuroprotective than a GLP-1 receptor agonist in key biomarkers of neuronal degeneration.

  11. Neuroprotective effects of the AMPA antagonist PNQX in oxygen-glucose deprivation in mouse hippocampal slice cultures and global cerebral ischemia in gerbils

    DEFF Research Database (Denmark)

    Montero, Maria; Nielsen, Marianne; Rønn, Lars Christian B

    2007-01-01

    PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD) and in tr......PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD....... For comparison, other cultures were exposed to the NMDA antagonist MK-801 using the same protocol. Both PNQX and MK-801 displayed significant neuroprotective effects in all hippocampal subfields when present during and after OGD. When added just after OGD, only PNQX retained some neuroprotective effect. When...... stained for the neurodegeneration marker Fluoro-Jade B and immunostained for the astroglial marker glial fibrillary acidic protein revealed a significant PNQX-induced decrease in neuronal cell death and astroglial activation. We conclude that, PNQX provided neuroprotection against both global cerebral...

  12. Involvement of Rac1 and the actin cytoskeleton in insulin- and contraction-stimulated intracellular signaling and glucose uptake in mature skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke

    Type 2 Diabetes affects ~10 % of western adults and is associated with poor organ sensitivity to insulin that is secreted following a meal. Insulin resistance, particularly in the liver, fat, and skeletal muscle, is a key event in the pathogenesis of Type 2 Diabetes and contributes to hyperinsuli......Type 2 Diabetes affects ~10 % of western adults and is associated with poor organ sensitivity to insulin that is secreted following a meal. Insulin resistance, particularly in the liver, fat, and skeletal muscle, is a key event in the pathogenesis of Type 2 Diabetes and contributes...... understood. The aim of the current PhD was therefore to investigate the involvement of Rac1 and the actin cytoskeleton in the regulation of insulin- and contraction-stimulated glucose uptake in mature skeletal muscle. The central findings of this PhD thesis was that Rac1 was activated by both insulin...

  13. 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...... bicarbonate (Bicarb, 1 m; 350–500 ml) or an equal volume of normal saline (Sal) was infused intravenously at a constant rate during a ‘2000 m' maximal ergometer row in six male oarsmen (23 ± 2 years; mean ± s.d.). During the Sal trial, pH decreased from 7.41 ± 0.01 at rest to 7.02 ± 0.02 but only to 7.36 ± 0...

  14. 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

    We evaluated cerebral perfusion, oxygenation, and metabolism in eleven young (age 22 ± 1 years) and nine older (age 66 ± 2 years) individuals at rest and during cycling exercise at low (25% W(max)), moderate (50% W(max)), high (75% W(ma)) and exhaustive (100% W(max)) workloads. Mean middle cerebral......)), 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......(max) was ~33% lower in the older group. Exercise increased MAP and CO in both groups (P...

  15. 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...... overweight males were included in a randomized, controlled study (training: n = 10; control: n = 7). Arterial and internal jugular venous catheterization was used to determine concentration differences for oxygen, glucose, and lactate across the brain and the oxygen-carbohydrate index [molar uptake of oxygen...... with a lower plasma epinephrine concentration (P training manifested when 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

  16. Intratumoral Heterogeneous F 18 Fluorodeoxyglucose Uptake Corresponds with Glucose Transporter 1 and Ki-67 Expression in a Case of Krukenberg Tumor: Localization of Intratumoral Hypermetabolic Focus by Fused PET/MR

    Energy Technology Data Exchange (ETDEWEB)

    Im, Hyung Jun; Kim, Youg il; Kim, Woo Ho; Kim, Seung Hyup; Kang, Keon Wook [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    The expression of glucose transporters (Glut 1, Glut 3), Hexokinase II, and Ki-67 has been proposed to explain intratumoral heterogeneous F-18 fluorodeoxyglucose (FDG) uptake. We report a case of Krukenberg tumor with intratumoral heterogeneous FDG uptake which corresponded well with the expression tomography (PET)/magnetic resonance (MR) imaging was helpful for localizing the metabolically active area in the tumor specimen. This report elucidates the relationship between the intratumoral heterogeneous FDG uptake and biologic heterogeneity, and shows the usefulness of PET/MR in research on intratumoral heterogeneity.

  17. Gluconeogenesis and fasting in cerebral malaria

    NARCIS (Netherlands)

    van Thien, H.; Ackermans, M. T.; Weverling, G. J.; Dang Vinh, T.; Endert, E.; Kager, P. A.; Sauerwein, H. P.

    2004-01-01

    BACKGROUND: In healthy subjects after an overnight fast, glucose production is for approximately 50% derived from glycogenolysis. If the fast is prolonged, glucose production decreases due to a decline in glycogenolysis, while gluconeogenesis remains stable. In cerebral malaria, glucose production

  18. Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood-brain barrier Na/H exchanger.

    Science.gov (United States)

    O'Donnell, Martha E; Chen, Yi-Je; Lam, Tina I; Taylor, Kelleen C; Walton, Jeffrey H; Anderson, Steven E

    2013-02-01

    Cerebral edema forms in the early hours of ischemic stroke by processes involving increased transport of Na and Cl from blood into brain across an intact blood-brain barrier (BBB). Our previous studies provided evidence that the BBB Na-K-Cl cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema and infarct in rats subjected to permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP. The present study was conducted to further investigate the possibility that a BBB Na/H exchanger also participates in edema formation during ischemic stroke. Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic resonance spectroscopy Na spectroscopy, respectively, for up to 210 minutes. We found that intravenous administration of the specific Na/H exchange inhibitor HOE-642 significantly decreased brain Na uptake and reduced cerebral edema, brain swelling, and infarct volume. These findings support the hypothesis that edema formation and brain Na uptake during the early hours of cerebral ischemia involve BBB Na/H exchanger activity as well as Na-K-Cl cotransporter activity.

  19. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  20. MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Kim, Joonyoung; Jones, Lynne A.; Mercer, Nicole M.; Engelbach, John A.; Sharp, Terry L.; Welch, Michael J. E-mail: welchm@mir.wustl.edu

    2002-11-01

    PET has been used to monitor changes in tumor metabolism in breast cancer following hormonal therapy. This study was undertaken to determine whether PET imaging could evaluate early metabolic changes in prostate tumor following androgen ablation therapy. Studies were performed comparing two positron-emitting tracers, {sup 18}F-FDG and {sup 11}C-acetate, in Sprague-Dawley male rats to monitor metabolic changes in normal prostate tissue. Additional studies were performed in nude mice bearing the CWR22 androgen-dependent human prostate tumor to evaluate metabolic changes in prostate tumor. In rats, for the androgen ablation pretreatment, 1 mg diethylstilbestrol (DES) was injected subcutaneously 3 and 24 hours before tracer injection. For androgen pretreatment, 500 {mu}g dihydrotestosterone (DHT) was injected intraperitoneally 2 and 6 hours before tracer injection. The rats were divided into three groups, Group A (no-DES, no-DHT, n = 18), Group B (DES, no-DHT, n = 18) and Group C (DES, DHT, n = 18). In each group, 10 animals received {sup 18}F-FDG, whereas the remaining eight animals were administered {sup 11}C-acetate. Rats were sacrificed at 120 min post-injection of {sup 18}F-FDG or 30 min post-injection of {sup 11}C-acetate. Pretreatment of the mouse model using DHT (200 {mu}g of DHT in 0.1 mL of sunflower seed oil) or DES (200 {mu}g of DES in 0.1 mL of sunflower seed oil) was conducted every 2 days for one week. Mice were imaged with both tracers in the microPET scanner (Concorde Microsystems Inc.). DES treatment caused a decrease in acetate and glucose metabolism in the rat prostate. Co-treatment with DHT maintained the glucose metabolism levels at baseline values. In the tumor bearing mice, similar effects were seen in {sup 18}F-FDG study, while there was no significant difference in {sup 11}C-acetate uptake. These results indicate that changes in serum testosterone levels influence {sup 18}F-FDG uptake in the prostate gland, which is closely tied to glucose

  1. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    International Nuclear Information System (INIS)

    Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E.; Pi, Jingbo

    2011-01-01

    Highlights: → In 3T3-L1 adipocytes iAs 3+ decreases insulin-stimulated glucose uptake. → iAs 3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs 3+ activates the cellular adaptive oxidative stress response. → iAs 3+ impairs insulin-stimulated ROS signaling. → iAs 3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs 3+ ) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs 3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs 3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in

  2. Cerebral Blood Flow and Aβ-Amyloid Estimates by WARM Analysis of [11C]PiB Uptake Distinguish among and between Neurodegenerative Disorders and Aging.

    Science.gov (United States)

    Rodell, Anders B; O'Keefe, Graeme; Rowe, Christopher C; Villemagne, Victor L; Gjedde, Albert

    2016-01-01

    Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [ 11 C]Pittsburgh Compound B ([ 11 C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer's disease, and healthy volunteers. The method introduces two approaches to the identification of brain pathology related to amyloid accumulation, (1) a novel analysis of amyloid binding based on the late washout of the tracer from brain tissue, and (2) the simultaneous estimation of absolute cerebral blood flow indices (sCBF) from the early accumulation of the tracer in brain tissue. Objective: We tested the hypothesis that a change of cerebral blood flow is correlated with the degree of tracer [ 11 C]PiB retention, reflecting dendritic spine pathology and consequent inhibition of brain energy metabolism and reduction of blood flow by neurovascular coupling in neurodegenerative disorders, including Alzheimer's disease. Methods: Previously reported images of [ 11 C]PiB retention in brain of 29 subjects with cognitive impairment or dementia [16 Alzheimer's Disease (AD), eight subjects with dementia with Lewy bodies (DLB), five patients with frontotemporal lobar degeneration (FTLD), five patients with mild cognitive impairment, and 29 age-matched healthy control subjects (HC)], underwent analysis of PiB delivery and retention by means of WARM for quantitation of [ 11 C]PiB's binding potentials ( BP ND ) and correlated surrogate cerebral blood flow (sCBF) estimates, based on the [ 11 C]PiB images, compared to estimates by conventional Standard Uptake Value Ratio (SUVR) of [ 11 C]PiB retention with cerebellum gray matter as reference. Receiver Operating Characteristics (ROC) revealed the power of discrimination among estimates. Results: For AD, the discriminatory power of [ 11 C]PiB binding potential ( BP ND ) by WARM exceeded the power of SUVR that in turn exceeded

  3. The Uptake of Screening for Type 2 Diabetes and Prediabetes by Means of Glycated Hemoglobin versus the Oral Glucose Tolerance Test among 18 to 60-Year-Old People of South Asian Origin: A Comparative Study

    NARCIS (Netherlands)

    van Valkengoed, Irene G. M.; Vlaar, Everlina M. A.; Nierkens, Vera; Middelkoop, Barend J. C.; Stronks, Karien

    2015-01-01

    Direct comparisons of the effect of a glycated haemoglobin measurement or an oral glucose tolerance test on the uptake and yield of screening in people of South Asian origin have not been made. We evaluated this in 18 to 60-year-old South Asian Surinamese. We invited 3173 South Asian Surinamese for

  4. Optimizing {sup 18}F-FDG PET/CT imaging of vessel wall inflammation: the impact of {sup 18}F-FDG circulation time, injected dose, uptake parameters, and fasting blood glucose levels

    Energy Technology Data Exchange (ETDEWEB)

    Bucerius, Jan [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, P.O. Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht (Netherlands); University Hospital, RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany); Mani, Venkatesh; Fayad, Zahi A. [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, P.O. Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Mount Sinai School of Medicine, Department of Cardiology, Zena and Michael A. Weiner Cardiovascular Institute and Marie-Josee and Henry R. Kravis Cardiovascular Health Center, New York, NY (United States); Moncrieff, Colin [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, One Gustave L. Levy Place, P.O. Box 1234, New York, NY (United States); Mount Sinai School of Medicine, Department of Radiology, New York, NY (United States); Machac, Josef [Mount Sinai School of Medicine, Division of Nuclear Medicine, Department of Radiology, New York, NY (United States); Fuster, Valentin [Mount Sinai School of Medicine, Department of Cardiology, Zena and Michael A. Weiner Cardiovascular Institute and Marie-Josee and Henry R. Kravis Cardiovascular Health Center, New York, NY (United States); The Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid (Spain); Farkouh, Michael E. [Mount Sinai School of Medicine, Department of Cardiology, Zena and Michael A. Weiner Cardiovascular Institute and Marie-Josee and Henry R. Kravis Cardiovascular Health Center, New York, NY (United States); Mount Sinai School of Medicine, Cardiovascular Imaging Clinical Trials Unit, New York, NY (United States); Tawakol, Ahmed [Massachusetts General Hospital, Harvard University, Cardiac MR PET CT Program, Boston, MA (United States); Rudd, James H.F. [Cambridge University, Division of Cardiovascular Medicine, Cambridge (United Kingdom)

    2014-02-15

    {sup 18}F-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging. Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values ({sub mean}SUV{sub max}), target-to-background ratios ({sub mean}TBR{sub max}) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake. Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aortic{sub mean}SUV{sub max} values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotid{sub mean}TBR{sub max} values. Prescan glucose levels were negatively associated with aortic and carotid{sub mean}TBR{sub max} and carotid{sub mean}SUV{sub max} values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake. FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol

  5. False-positive uptake on 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in oncological imaging

    International Nuclear Information System (INIS)

    Culverwell, A.D.; Scarsbrook, A.F.; Chowdhury, F.U.

    2011-01-01

    With the increasing utilization of integrated positron-emission tomography/computed tomography (PET/CT) using the glucose analogue 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG) in oncological imaging, it is important for radiologists and nuclear medicine physicians to be aware that FDG uptake is not specific for malignancy, as many different physiological variants and benign pathological conditions can also exhibit increased glucose metabolism. Such false-positive FDG uptake often arises outside the area of primary interest and may mimic malignant disease, thereby confounding accurate interpretation of PET/CT studies. With the use of illustrative clinical cases, this article will provide a systematic overview of potential interpretative pitfalls and illustrate how such unexpected findings can be appropriately evaluated.

  6. Flavonoids from Enicostema littorale blume enhances glucose uptake of cells in insulin resistant human liver cancer (HepG2) cell line via IRS-1/PI3K/Akt pathway.

    Science.gov (United States)

    Mokashi, Priyanka; Khanna, Aparna; Pandita, Nancy

    2017-06-01

    Diabetes mellitus has spread over the world with 347 million people affected. Insulin resistance is a main pathogenic event in Type 2 Diabetes Mellitus (T2DM) leading to a reduction in glucose uptake by peripheral tissue and increased hepatic glucose output. In this study, we have isolated four flavonoid rich fractions fraction A (FA), fraction B (FB), fraction C (FC) and fraction D (FD) from Enicostema littorale. All the fractions were preliminary screened for TLC fingerprinting, total flavonoid content. Total eight flavonoids were identified by LC/MS. Insulin resistant HepG2 (IR/HepG2) model was established by inducing insulin resistance in HepG2 cells to investigate the effect of these fractions on IR/HepG2 cell line for their glucose uptake. The results showed the significant dose dependant increase in glucose uptake of cells treated with FD. It showed significant activity at a concentration of 10μg/ml. The LC/MS results of FD demonstrated the presence of C-glycoside Swertisin which could be responsible for the effect. Further, to investigate the mechanism of action, gene expression for insulin receptor substrate 1 (IRS-1), protein kinase B (Akt-2) and glucose transporter 4 (GLUT-4) genes were evaluated by real time PCR. A significant upregulation of these genes was observed in FD treated samples, thereby indicating the enhancement of glucose uptake rate of cells via IRS-1/PI3K/Akt pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli.

    Science.gov (United States)

    Millard, Pierre; Smallbone, Kieran; Mendes, Pedro

    2017-02-01

    The metabolism of microorganisms is regulated through two main mechanisms: changes of enzyme capacities as a consequence of gene expression modulation ("hierarchical control") and changes of enzyme activities through metabolite-enzyme interactions. An increasing body of evidence indicates that hierarchical control is insufficient to explain metabolic behaviors, but the system-wide impact of metabolic regulation remains largely uncharacterized. To clarify its role, we developed and validated a detailed kinetic model of Escherichia coli central metabolism that links growth to environment. Metabolic control analyses confirm that the control is widely distributed across the network and highlight strong interconnections between all the pathways. Exploration of the model solution space reveals that several robust properties emerge from metabolic regulation, from the molecular level (e.g. homeostasis of total metabolite pool) to the overall cellular physiology (e.g. coordination of carbon uptake, catabolism, energy and redox production, and growth), while allowing a large degree of flexibility at most individual metabolic steps. These properties have important physiological implications for E. coli and significantly expand the self-regulating capacities of its metabolism.

  8. Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Pierre Millard

    2017-02-01

    Full Text Available The metabolism of microorganisms is regulated through two main mechanisms: changes of enzyme capacities as a consequence of gene expression modulation ("hierarchical control" and changes of enzyme activities through metabolite-enzyme interactions. An increasing body of evidence indicates that hierarchical control is insufficient to explain metabolic behaviors, but the system-wide impact of metabolic regulation remains largely uncharacterized. To clarify its role, we developed and validated a detailed kinetic model of Escherichia coli central metabolism that links growth to environment. Metabolic control analyses confirm that the control is widely distributed across the network and highlight strong interconnections between all the pathways. Exploration of the model solution space reveals that several robust properties emerge from metabolic regulation, from the molecular level (e.g. homeostasis of total metabolite pool to the overall cellular physiology (e.g. coordination of carbon uptake, catabolism, energy and redox production, and growth, while allowing a large degree of flexibility at most individual metabolic steps. These properties have important physiological implications for E. coli and significantly expand the self-regulating capacities of its metabolism.

  9. Proliferation is associated with 2-deoxy-D-[1-{sup 3}H]glucose uptake by T47D breast tumour and SW480 and SW620 colonic tumour cells

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Timothy A.D.; Titley, Jennifer C.; McCready, V. Ralph

    1998-07-01

    The interpretation of therapy-induced changes in the uptake of fluorodeoxyglucose by tumours, detected using PET, is dependent on which tumour characteristics are associated with its uptake. In this study the relationship between proliferation (S-phase fraction) and the uptake of 2-deoxy-D-[1-{sup 3}H]glucose by T47D breast tumour and SW480 and SW620 colonic tumour cells was measured between 2 and 12 days after seeding. Strong correlations (p<0.001) were observed between viable cell number and the uptake of 2-deoxy-D-[1-{sup 3}H]glucose/flask by each of the cell lines. Uptake of this compound was also found to correlate with S phase fraction in the T47D line (p<0.05) and the SW480 (p<0.01) and the SW620 (p<0.001) colonic tumour lines. The findings of the present study suggest that therapy-induced changes in the uptake of this compound may at least partially reflect changes in proliferative fraction.

  10. BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

    DEFF Research Database (Denmark)

    Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise

    2016-01-01

    The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID...... deficiency protected organotypic hippocampal slice cultures in vitro from neuronal injury induced by oxygen-glucose deprivation. In vivo, BID-knockout (KO) mice and wild type (WT) mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) to induce focal cerebral ischemia...... between BID-KO and WT mice. The inflammatory response was reduced by BID deficiency as indicated by a change in microglial/leukocyte response. In conclusion, our data suggest that BID deficiency is neuroprotective in an in vitro model and modulates the inflammatory response to focal cerebral ischemia...

  11. Family of Ricinus communis Monosaccharide Transporters and RcSTP1 in Promoting the Uptake of a Glucose-Fipronil Conjugate.

    Science.gov (United States)

    Mao, Gen-Lin; Yan, Yin; Chen, Yan; Wang, Bing-Feng; Xu, Fei-Fei; Zhang, Zhi-Xiang; Lin, Fei; Xu, Han-Hong

    2017-08-02

    Enhancing the systemic distribution of a bioactive compound by exploiting the vascular transport system of a plant presents a means of reducing both the volume and frequency of pesticide/fungicide application. The foliar uptake of the glucose-fipronil conjugate N-[3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazol-5-yl]-1-(β-d-glucopyranosyl)-1H-1,2,3-triazole-4-methanamine (GTF) achieved in castor bean (Ricinus communis) and its transport via the phloem are known to be mediated by monosaccharide transporter(s) [MST(s)], although neither the identity of the key MST(s) involved nor the mechanistic basis of its movement have yet to be described. On the basis of homology with Arabidopsis thaliana sugar transporters, the castor bean genome was concluded to harbor 53 genes encoding a sugar transporter, falling into the eight previously defined subfamilies INT, PMT, VGT, STP, ERD6, pGlucT, TMT, and SUT. Transcriptional profiling identified the product of RcSTP1 as a candidate for mediating GTF uptake, because this gene was induced by exposure of the plant to GTF. When RcSTP1 was transiently expressed in onion epidermis cells, the site of RcSTP1 deposition was shown to be the plasma membrane. A functional analysis based on RcSTP1 expression in Xenopus laevis oocytes demonstrated that its product has a high affinity for GTF. The long-distance root-to-shoot transport of GTF was enhanced in a transgenic soybean chimera constitutively expressing RcSTP1.

  12. 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

  13. Non-invasive estimation of hepatic glucose uptake from [{sup 18}F]FDG PET images using tissue-derived input functions

    Energy Technology Data Exchange (ETDEWEB)

    Kudomi, N.; Jaervisalo, M.J.; Borra, R.; Viljanen, A.; Viljanen, T.; Knuuti, J. [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Kiss, J.; Savunen, T. [University of Turku, Department of Surgery, Turku (Finland); Iida, H. [National Cardiovascular Center-Research Institute, Department of Investigative Radiology, Advanced Medical Engineering Center, Suita, Osaka (Japan); Nuutila, P. [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); University of Turku, Department of Medicine, Turku (Finland); Iozzo, P. [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); National Research Council, Institute of Clinical Physiology, Pisa (Italy)

    2009-12-15

    The liver is perfused through the portal vein and hepatic artery. Quantification of hepatic glucose uptake (HGU) using PET requires the use of an input function for both the hepatic artery and portal vein. The former can be generally obtained invasively, but blood withdrawal from the portal vein is not practical in humans. The aim of this study was to develop and validate a new technique to obtain quantitative HGU by estimating the input function from PET images. Normal pigs (n = 12) were studied with [{sup 18}F]FDG PET, in which arterial and portal blood time-activity curves (TAC) were determined invasively to serve as reference measurements. The present technique consisted of two characteristics, i.e. using a model input function and simultaneously fitting multiple liver tissue TACs from images by minimizing the residual sum of square between the tissue TACs and fitted curves. The input function was obtained from the parameters determined from the fitting. The HGU values were computed by the estimated and measured input functions and compared between the methods. The estimated input functions were well reproduced. The HGU values, ranging from 0.005 to 0.02 ml/min per ml, were not significantly different between the two methods (r = 0.95, p < 0.001). A Bland-Altman plot demonstrated a small overestimation by the image-derived method with a bias of 0.00052 ml/min per g for HGU. The results presented demonstrate that the input function can be estimated directly from the PET image, supporting the fully non-invasive assessment of liver glucose metabolism in human studies. (orig.)

  14. Insulin-Like Growth Factor (IGF Binding Protein-2, Independently of IGF-1, Induces GLUT-4 Translocation and Glucose Uptake in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Biruhalem Assefa

    2017-01-01

    Full Text Available Insulin-like growth factor binding protein-2 (IGFBP-2 is the predominant IGF binding protein produced during adipogenesis and is known to increase the insulin-stimulated glucose uptake (GU in myotubes. We investigated the IGFBP-2-induced changes in basal and insulin-stimulated GU in adipocytes and the underlying mechanisms. We further determined the role of insulin and IGF-1 receptors in mediating the IGFBP-2 and the impact of IGFBP-2 on the IGF-1-induced GU. Fully differentiated 3T3-L1 adipocytes were treated with IGFBP-2 in the presence and absence of insulin and IGF-1. Insulin, IGF-1, and IGFBP-2 induced a dose-dependent increase in GU. IGFBP-2 increased the insulin-induced GU after long-term incubation. The IGFBP-2-induced impact on GU was neither affected by insulin or IGF-1 receptor blockage nor by insulin receptor knockdown. IGFBP-2 significantly increased the phosphorylation of PI3K, Akt, AMPK, TBC1D1, and PKCζ/λ and induced GLUT-4 translocation. Moreover, inhibition of PI3K and AMPK significantly reduced IGFBP-2-stimulated GU. In conclusion, IGFBP-2 stimulates GU in 3T3-L1 adipocytes through activation of PI3K/Akt, AMPK/TBC1D1, and PI3K/PKCζ/λ/GLUT-4 signaling. The stimulatory effect of IGFBP-2 on GU is independent of its binding to IGF-1 and is possibly not mediated through the insulin or IGF-1 receptor. This study highlights the potential role of IGFBP-2 in glucose metabolism.

  15. 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.

  16. Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

    Science.gov (United States)

    Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi

    2016-05-19

    Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Mismatched uptake of Tc-99m-ECD and Tc-99m-HMPAO in subacute cerebral infarction: Tc-99m-ECD for viability and Tc-99m-HMPAO for flow restoration

    International Nuclear Information System (INIS)

    Lee, D. S.; Hyun, I. Y.; Kim, S. K.

    1997-01-01

    Tc-99m-HMPAO reflects tissue perfusion but Tc-99m-ECD uptake is affected by tissue viability in addition to tissue perfusion which the varied state of cellular retention of Tc-99m-ECD reflects. Luxuriously perfused area on Tc-99m-HMPAO SPECT implies that this cortex was already reperfused either spontaneously or after thrombolysis and that accompanied paralysis of vascular reactivity in those zones warms progressive deterioration. We tried to find out if we can use sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT to reveal cortical perfusion and severity and range of risky areas of cerbral cortex despite reperfusion in sub-acute infarction. In 13 patients (M ; F =7 : 6, mean age 57 (range: 26-84)) with cortical (n=12) and basal ganglia infarction (1), we performed sequential Tc-99m-ECD/Tc-99m-HMPAO SPECT at the same position. At first, 555 MBq of Tc-99m-ECD was injected and imaged and then 1110 MBq of Tc-99m-HMPAO was injected again and imaged with the patients in situ, and the first image (Tc-99m-ECD) and the subtracted image (2nd- 1st : Tc-99m-HMPAO) were compared slice by slice. Study was done from 3 days to 31 days (16±9) after ictus. Tc-99m-ECD uptake was always less than or equal to Tc-99m-HMPAO uptake at the lesion in all cases. Luxury perfusion was prominent in four patients. Mismatched uptake was found in 10 patients. Severity of mismatch showed diverse spectrum and was ranged from total middle cerebral artery territory (1 case) to peripheral thin zones around infarction (2 cases). The other 7 showed intermediate amount of tissues with mismatch , i.e., Tc-99m-ECD defects where Tc-99m-HMPAO uptake is in part increased, normal or decreased. Upon discharge, patients having more uptake with Tc-99m-ECD predicted improvement. Patients having mismatched uptake went dichotomous way. In conclusion, Tc-99m-ECD/Tc-99m-HMPAO sequential SPECT is feasible and reveal both tissue perfusion (Tc-99m-HMPAO ) and discrepant Tc-99m-ECD uptake probably reflecting viability in acute or

  18. Mismatched uptake of Tc-99m-ECD and Tc-99m-HMPAO in subacute cerebral infarction: Tc-99m-ECD for viability and Tc-99m-HMPAO for flow restoration

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D. S.; Hyun, I. Y.; Kim, S. K. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)] [and others

    1997-07-01

    Tc-99m-HMPAO reflects tissue perfusion but Tc-99m-ECD uptake is affected by tissue viability in addition to tissue perfusion which the varied state of cellular retention of Tc-99m-ECD reflects. Luxuriously perfused area on Tc-99m-HMPAO SPECT implies that this cortex was already reperfused either spontaneously or after thrombolysis and that accompanied paralysis of vascular reactivity in those zones warms progressive deterioration. We tried to